Peking Union Medical College, China
Dr. De-Pei Liu is currently a professor of National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC). Dr. Liu graduated with a Ph.D. from CAMS & PUMC in 1986. He completed his Postdoctoral Fello- wship in molecular biology at University of California, San Francisco (UCSF), and was promoted to be a Professor of CAMS & PUMC in 1992. Dr. Liu’s research expertise is molecualr mechanisms of cardiovascular diseases, gene regulation and gene therapy. He has published more than 120 original research articles and invited reviews. Throughout his academic career, Dr. Liu has received numerous awards including three items of awards of Advance of Science and Technology, the Ministry of Health, P.R.China and one item of award of the National Natural Sciences Foundation. He is also serving as a member of Chinese Academy of Engineering (CAE), member of Institute of Medicine (IOM) of the National Academies and member of Third World Academy of Sciences (TWAS).
Protective Roles of SIRT1 in arteriosclerotic cardiovascular disease
Depei Liu , Ph.D.
Cardiovascular diseases are the leading causes of death and disability in the world. A better understanding for the molecular mechanism in the development of cardiovascular diseases will provide more strategies for their diagnosis, treatment and prevention. Sirtuin 1 (SIRT1), the closest homology to the yeast Sir2 protein in human sirtuins, has been implicated in aging, metabolism, and tolerance to oxidative stress via its ability to deacetylate a variety of substrates, including histones, transcription factors, and coregulators. The results of recent studies from our lab have demonstrated that endothelial SIRT1 is an anti-atherosclerosis factor and prevents the hyperlipidemia and hyperglycemia-induced endothelial damages. Moreover, SIRT1 acts as a novel modulator linking the coordinated responses of vascular smooth muscle cells (VSMCs) to injury. We summarized the beneficial effects of SIRT1 in vascular system and proposed that SIRT1 and its activators can become novel therapeutic targets for arteriosclerotic cardiovascular disease.
Dr. Hongliang Li is Professor of Medicine at the Wuhan University. Dr. Li currently serves as the Director of Collaborative Innovation Center of Model Animal and Vice Director of Cardiovascular Research Institute of Wuhan University. After obtaining his PhD from the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, he pursued his post-doctoral trainings in Joslin Diabetes Center of Harvard Medical School, and department of Cardiology at the University of Toronto. In past ten years, he has published over 60 peer reviewed papers in highly impacted journals including Circulation, Circulation Research, Hepatology, PNAS, Diabetes, Hypertension, and Cardiovascular Research. His research achievement is also reflected by his great success in grant application. Since 2008, he has obtained over $10 million research grants from Ministry of Science and Technology, Ministry of Education of the People’s Republic of China and National Natural Science Foundation of China. Dr. Li’s current research programs are focused on defining the novel roles of interferon regulatory factors family in stroke, diabetes, hepatic dysfunction, atherosclerosis & restenosis, myocardial infarction, cardiac hypertrophy and diabetic cardiovascular complications. Dr. Li is also interested in the development of biotechnologies for genome manipulation, phenotypic characterization, and identification of genetic components of complex human disease. He has established a perfect platform for making transgenic and knockout animal models including mouse, rat, and rabbit. His center has offered transgenic production, gene targeting, and generation of chimeras of mice, rats and rabbits. His group has developed over 500 strains of gene knock-out and transgenic mice and 70 strains of knockout rats, all of which have been made available to Chinese scientists. His work has greatly facilitated the development of the model animals in China.
Ming-Hui Zou, M.D.,Ph.D.
University of Oklahoma Health Science, USA
Ming-Hui Zou, Ph.D. is the George Lynn Cross Research Professor of the University of Oklahoma. Dr. Zou is Professor of Medicine (tenure), and Professor of Biochemistry and Molecular Biology (tenure) at University of Oklahoma Health Science Center. He currently serves as the Chief of the section of Molecular Medicine and vice chairman for research, Department of Medicine. He also holds the Travis Endowed Chair in Endocrinology (since 2005) and the Warren Endowed Chair Professorship in Diabetes Research (since 2010) at the University of Oklahoma Health Science Center.
Dr. Zou has been productively working in the area of cardiovascular biology and diseases for 20 years. Dr. Zou’s ongoing research programs focus on the means to sense oxidative stress, reduce it, or ameliorate the body’s adverse response to it. Dr. Zou was instrumental in examining the role of nitric oxide and oxidative stress in the regulation of blood flow and vascular function. He performed elegant, state-of-the-art studies to show that the selective modification of two key proteins, prostacyclin synthase and endothelial nitric oxide synthase, is critical in the deregulation of vessel function from nitric oxide and superoxide. Dr. Zou’s group was also the first to demonstrate that the AMP-activated kinase (AMPK), a key enzyme in the regulation of energy metabolism, obesity, diabetes, and cardiovascular diseases, functions as a sensor and regulator of oxidative stress. Dr. Zou’s contributions in this area are significant and his work represents outstanding breakthrough research, which has been recognized by many other investigators in the fields. An independent investigator of the National Institutes of Health, the Juvenile Diabetes Research Foundation International (JDRF), and the American Diabetes Association, and a National Scientist Development (SDG) and National Established Investigator (EIA) awardee of the American Heart Association, Dr. Zou has used these (and many other awards) to make scientific observations in fields with great potential for immediate clinical relevance. Since 2005, Dr. Zou has served on several national study panels such as the National Institutes of Health, American Heart Association, and American Diabetes Association and on many international panels including the National Science Foundation of China, the Research Grant Council and the University of Grant Committee of Hong Kong, the Wellcome Trust of England, and German Science Foundation (DFG). He is also the Editor-in-chief for the journals “Diabetes, Metabolic Syndrome and Obesity” “World Journal of Diabetes” and has served the editorial boards of many prestigious journals including ATVB, Diabetes, etc. In past three years, he has published 45 peer reviewed papers in highly impacted journals including Nature Medicine, Circulation、Circulation Research, J. Clin. Invest., Diabetes, Mol. Cell. Biol. Atherosclerosis, Vascular Biology, and Thrombosis、J. Biol. Chem., Hypertension.In 2008 he was elected to the American Society for Clinical Investigation, one of the United States’ oldest honor societies of physician-scientists, membership in which reflects accomplishments by its members at an early stage (<45 years old) in their careers.
AMPK alpha 1, monocyte differentiation, and atherosclerosis
Ming-Hui Zou, M.D., Ph.D.
Atherosclerosis is characterized by early accumulation of lipids and macrophages in the intimal layer of the arterial wall. Infiltration of monocytes into the arterial intima, where the monocytes differentiate into tissue macrophages by growth factors such as monocyte colony-stimulating factor (M-CSF) and/or oxidized LDL, appears to be the critical growth factor for macrophage survival and differentiation. In the absence of growth factors, either M-CSF or GMCSF, monocytes undergo spontaneous apoptosis. Although previous studies have shown that oxidized LDL alone at low concentrations can promote cell survival and M-CSF has been detected in human atherosclerotic lesions both at mRNA and protein level, the molecular link between monocyte differentiation and survival remains poorly defined. AMP-activated protein kinase (AMPK) is an energy sensor consisting of a catalytic subunit, α, and two regulatory subunits, α1 and α2. The catalytic subunit of AMPK has two isoforms, α1 and α2, which have different tissue expression patterns. Our recently published data indicate that deletion of the AMPKα2 isoform accelerates atherosclerotic lesion formation by increasing reactive oxygen species levels and inducing endoplasmic reticulum stress. AMPKα1 isoform is predominant isoform in vascular cells and macrophages. The effects of AMPK α1 on atherosclerosis are unknown. In my talk, I will discuss how AMPK α1 differentially affects atherosclerotic progression at different lesion stages through regulating monocyte to macrophage differentiation and mononuclear phagocyte survival.
Joseph A. Vita, M.D.
Boston University School of Medicine, USA
Dr. Vita is a Professor of Medicine at Boston University School of Medicine and Associate Chief for Academic Affairs in the Section of Cardiovascular Medicine. He earned a BS degree in Chemistry at Yale College and completed his MD degree at Columbia University College of Physicians and Surgeons. He trained in Internal Medicine and was Chief Medical Resident at Presbyterian Hospital in New York City. Dr. Vita then completed clinical training in Cardiology and Interventional Cardiology at the Brigham and Women’s Hospital.
Dr. Vita currently practices in-patient and consultative cardiology at Boston Medical Center. He spends the majority of his time performing clinical and translational research and training fellows and junior faculty in the conduct of research. His research focuses on vascular biology, and he has a particular interest in endothelial dysfunction in atherosclerosis. Dr. Vita’s research is funded by the National Institutes of Health and he is the Director of an NIH K12 Research Training Program in Vascular Medicine.
Dr. Vita is a Fellow of the American Heart Association, the American College of Cardiology, and the American College of Nutrition. He is a member of the American Society for Clinical Investigation, the Association of University Cardiologists, and the Society for Vascular Medicine. He is a past member of the Cardiovascular Board of the American Board of Internal Medicine. Dr. Vita currently serves as the Deputy Editor of the journal Circulation. He was recently named Editor-in-Chief of the Journal of the American Heart Association (JAHA), the AHA’s new open access journal.
Endothelial Dysfunction in Patients with Metabolic Disease
Joseph A. Vita, M.D.
There is growing recognition that the vascular endothelium plays a central role in the regulation of vascular homeostasis. Abnormalities of endothelium-dependent vasodilation are detectable at all stages of atherosclerosis. In addition to loss of the bioactivity of endothelium-derived nitric oxide, these conditions are also associated with abnormalities of many other aspects of “endothelial function” including control of thrombosis, inflammation, and intimal growth. Patients with type 2 diabetes mellitus, obesity, and the metabolic syndrome, have increased risk for cardiovascular disease, and such patients also display endothelial dysfunction. For example, cross-sectional studies have demonstrated loss of brachial artery flow-mediated dilation in patients with diabetes mellitus, the metabolic syndrome, and elevated HOMA-IR index. We recently observed the rapid onset of endothelial dysfunction in the setting of acute insulin resistance induced by a short period of bed rest. Insulin resistance and endothelial dysfunction also develop during infusion of Intralipid, which increases circulating free fatty acids. Insulin sensitizing drugs improve endothelial function in patients with diabetes mellitus. Recent studies suggest links between mitochondria dysfunction and endothelial dysfunction in patients with type 2 diabetes mellitus. These studies provide insight the mechanistic links between syndromes of insulin resistance and cardiovascular disease and may suggest new approaches for patient management.
5、 Biographical Sketch
Aruni Bhatnagar, Ph.D.
University of Louisville, USA
Personal Statement: My research during my graduate and post-doctoral training was focused on elucidating the mechanisms by which free radicals and products of lipid peroxidation affect the electrophysiological properties of cardiac myocytes. I have continued to work on this area for the last 25 years. I am currently studying how lipid peroxidation products and the accumulation of aldehyde-modified proteins contribute to oxidative stress-induced by cardiac hypertrophy and heart failure. These studies are to better understand the myocardial toxicity of oxidative stress and lipid peroxidation derived aldehydes. I am currently a principal investigator on an R01 project that is to elucidate the metabolic pathways that regulate aldehyde metabolism in the heart and how these pathways are affected by hemodynamic stress. We expect that these studies will provide new insights into the mechanisms by which oxidative stress contributes to pathological hypertrophy and heart failure and might lead to the development of clinically-relevant strategies to prevent or attenuate cardiac dysfunction during heart failure. In addition, studies in my laboratory is also actively engaged in studying how pathways of oxidative stress and diabetes intersect and mutually reinforce each other, particularly in inducing cardiac dysfunction and decreasing specific stem cell populations. Since 2008, I am the Director of a comprehensive diabetes and obesity center. The main focus of the center is to investigate the mechanisms by which diabetes and obesity induce cardiovascular dysfunction and promote cardiovascular disease. A major direction in this endeavor is to develop a better understanding of how changes in specific stem cell populations affect the cardiovascular complications of diabetes. In this regard, the current project is a natural extension of our current interest and on-going research. It is the synthesis and culmination of our research in the fields of diabetes, oxidative stress, and stem cell biology. It is designed to fully exploit the expertise of the laboratory to elucidate how diabetes affects cardiac progenitor cells (CPCs) and how their regenerative capacity and efficacy could be enhanced in this condition.
These projects will be significantly facilitated by the acquisition of the CyTOF instrument as it will enable us to measure changes in the inflammatory cells in hypertrophic heart as well as diabetic stem cells with unprecedented ease and precision. This instrument will be critical in simultaneously measuring signaling pathways in complex cell populations, particularly in rare cells and would therefore its use could provide paradigm-shifting information that could move the field forward.
Environmental Cardiology: Effect of Particulate Air Pollution on Heart
Aruni Bhatnagar, Ph.D.
In this talk I will discuss the impact of the environment of heart disease, how different components of the natural, community and personal environment affect cardiovasc- ular disease risk. I will present a brief introduction of what particulate air pollution is: what are the type of particles that are present in ambient air and review studies showing the association between acute and chronic exposures to ambient air particulates and cardiovascular events and cardiovascular disease risk. I will discuss the underlying mechanisms and present our work showing that exposure to air particulates suppresses the levels of circulating stem cells and induces insulin resistance.
Kenneth Walsh, Ph.D.
Boston University School of Medicine, USA
Kenneth Walsh, PhD , is the Aram V. Chobanian Distinguished Professor of Medicine and the Director of the Whitaker Cardiovascular Institute in the Department of Medicine at Boston University School of Medicine. Dr. Walsh, who received his PhD in Biochemistry from the University of California, Berkeley, examines molecular events that drive cardiovascular cell growth, differentiation and apoptosis. Over the past decade his laboratory has been investigat- ing mechanisms of inter - tissue communication and how these systems contribute to physiological versus pathological tissue growth in the cardiovascular system. Dr. Walsh has published more than 300 scientific articles, some of which have been cited more that 1000 times. He is the recipient of multiple research grants from the National Institutes of Health, including a MERIT Award. He is a member of the CCHF study section for NIH, and he is an Associate Editor for the journal Circulation. Dr. Walsh serves on numerous editorial boards including Arteriosclerosis, Thrombosis and Vascular Biology, Circulation Research, Science Signaling and others. Dr. Walsh was the recipient of the Irvine F. Page Award from the Council on Arteriosclerosis and was previously an Established Investigator of the American Heart Association. He is a 2011 recipient of the Distinguished Investigator Award from the American Heart Association.
7、 Biographical Sketch
John F. Keaney, Jr. M.D.
UMASS Medical School, USA
Personal Statement: My laboratory has been investigating the redox environment of endothelial cells for the past 20 years. We have determined the intracellular antioxidant status that optimizes endothe- lial function and NO· bioactivity as well as perform -ing small-scale studies in humans to examine how endothelial function predicts vascular disease. Given that mitochondria are an important source of reactive oxygen species and help determine the cellular response to invronmental cues, my laboratory is in a unique position to investigate the role of the mitochondrion in modulating endothelial cell function.
Metabolic modulation of the endothelium
John F. Keaney, Jr. M.D.
Mitochondria, although required for cellular ATP production, are also known to have other important functions that may include modulating cellular responses to environmental stimuli. However, the mechanisms whereby mitochondria impact cellular phenotype are not yet clear. We investigated how mitochondria might influence endothelial cell phenotype. We found that models of hypertension and atherosclerosis were characterized by downregulation of mitochondrial biogenesis and the transcriptional coactivator, PGC-1. Restoring endothelial cell PGC-1 activity via endothelial-specific over expression preserved endothelial function in the setting of hypertension and atherosclerosis and limited both blood pressure elevation and lesion formation in these two models. The mechanism responsible for this effect was PGC-1α-mediated upregulation of eNOS activity. Since mitochondria also regulate their function via control of the proton gradient, we also examined the role of mitochondrial uncoupling protein 2 (UCP2) in endothelial function. We found that UCP2 was important for cellular proliferation and maintaining mitochondrial fission and fusion. Animals without UCP2 had defects in endothelial function manifest as premature endothelial senescence and impaired angiogenesis responses. Collectively, these data indicate that mitochondria are an important element for the normal function of the endothelium.
Michael Basson , M.D.
Dr. Michael Basson is a Senior Editor in the Nature medicine since 2003. As a graduate student in Jasper Rine's laboratory at University of California at Berkeley, Michael Basson studied the sterol biosynthetic pathway and its rate-limiting enzyme HMG-CoA reductase in baker's yeast. His postdoctoral work was on developmental genetics with Robert Horvitz at the Massachusetts Institute of Technology. He then worked in the biotech industry, first on the use of model organisms for drug discovery and then on angiogenesis from the perspective of treating cancer.
Patterson, Winston Campbell. M.D.
The University of North Carolina at Chapel Hill ,USA
Personal Statement：I am the Ernest Craige Disting- uished Professor of Medicine at the University of North Carolina at Chapel Hill (UNC), and I have been a member of UNC’s cardiology faculty since 2000. I also have appointments in the Departments of Pharmacology and Cell and Developmental Biology. I am the founding director of the UNC McAllister Heart Institute, a multidisciplinary center for the study of cardiovascular disease. I am an Established Investigator of the American Heart Association and a Burroughs-Wellcome Fund Clinical Scientist in Translational Research.
My research in molecular biology of the cardiac and vascular systems in genomic applications to cardiovascular biology is recognized internationally. My laboratory discovered CHIP, a protein that when interacting with heat shock proteins regulates triage decisions leading to refolding or degradation of denatured proteins. In addition, my lab has been an innovator in understanding the transcriptional programs regulating endothelial cell differentiation and cell type-specific gene expression. The ultimate goal of this work is to define the cascade of transcription factors involved in the endothelial cell differentiation, based on the assumption that these same factors will participate in cardiovascular disease.
Protein quality controls and cardiovascular diseases
Patterson, Winston Campbell, M.D.
Heart disease and heart failure remain the most common cause of death and disability in today’s society. Despite the fact that our understanding and treatment of acute cardiac conditions has improved greatly, the incidence of chronic cardiac conditions and the development of heart failure continue to rise. It is well known that protein homeostasis plays a pivotal role in the development of numerous pathologies. More recently however, there is a growing appreciation for the impact that misfolded proteins have on pathophysiological conditions, especially those of neurodegenerative diseases such as Huntington’s disease, Parkinson’s disease and, of course, Alzheimer’s disease. This in turn has led to the burgeoning idea that proteotoxicty, caused by misfolded proteins, may also be linked to the pathophysiology of common human cardiac diseases, and may in fact be a key contributor to the progression of heart failure. Therefore, by taking what has been learned regarding protein aggregation and subsequent proteotoxicity in neuropathologies, and applying it to cardiopathologies with similar biochemical hallmarks, it is possible that new cardioprotective treatments focused on preventing and/or reversing protein misfolding in the heart may be designed.
University of Kentucky, USA
Personal Statement: My laboratory has primarily focused on basic science of vascular diseases. Specifi- cally, this includes studying the mechanisms of athero- sclerosis and aortic aneurysms. I have been fortunate to interact with many early career scientists who have made major contributions to the research in my laboratory. This is includes contributions to significant numbers of published manuscripts. I have also proud of the high number of trainees from my laboratory that have attained individual grants from the American Heart Association and the National Science Foundation. They have also been successful in assimilating an impressive number of awards based on the scientific presentations. This includes poster and travel awards from both the University of Kentucky and from the American Heart Association. In addition to being fortunate to recruit talented individuals, the success has being assisted by focused on developing the talents of these individuals through a rigorously applied training program.
I have also been fortunate to have major administrative r esponsibilities of both the University of Kentucky and in other organizations. This includes being the D irector of the Saha Research Center and Senior Associate Dean of Research for the College of Medicine. I am hoping that these extensive administrative responsibilities convey sufficient experience for the committee to consider me as appropriately qualified to ascend to the directorship of this program.
Ann Marie Schmidt,M.D.
New York University, USA
Personal Statement: Dr. Schmidt’s laboratory dis- covered the multi-ligand receptor RAGE and her findings that RAGE bound advanced glycation endproducts, S100/calgranulins, high mobility group box-1 and amyloid-b peptide and b-sheet fibrils opened up novel areas for research in diabetes and its complications, inflammation, autoimmunity, tumor biology and amyloidoses. She has led studies using cellular and animal models to delineate key roles for RAGE signaling in these disorders, as blockade of RAGE or genetic deletion of the receptor exerts protective effects in murine models of diabetes macro- and microvascular complications, and in inflammatory settings. In addition to RAGE biology in disorders in which its ligands accumulate, Dr. Schmidt’s laboratory has discovered novel intracellular interacting molecules, specifically mDia1, a member of the formin family, which is required for RAGE signaling. Dr. Schmidt is studying the role of RAGE and mDia1 in the pathogenesis of diabetic atherosclerosis and atherosclerosis.
12、 Biographical Sketch
University of Ottawa, Canada
Peter Liu is the Scientific Director/Vice President of Research of the University of Ottawa Heart Institute, and also Professor of Medicine and Physiology at the University of Toronto and University of Ottawa. He was the former Scientific Director of the Institute of Circulatory and Respiratory Health at the Canadian Institutes of Health Research. Dr. Liu graduated from the University of Toronto Faculty of Medicine. He pursued post-doctoral fellowships in cardiovascular imaging and immunology at the Massachusetts General Hospital of Harvard Medical School, and clinical epidemiology at McMaster University.At the University of Toronto, he was the Heart & Stroke/Polo Chair Professor at the University Health Network, and also the inaugural Director of the Heart & Stroke/Richard Lewar Centre of Excellence in Cardiovascular Research at the University of Toronto.
His research focuses on the pathophysiology and clinical outcomes of heart failure from bench to bedside.His team has elucidated the role of inflammation in changing heart structure and function, and potential novel treatment targets in heart failure. His laboratory has also identified how environmental insults such as viruses and pressure load can accelerate heart failure and coronary artery disease, and is developing novel vaccines to prevent these complications. To unravel the evolution of chronic diseases, his team is also pursuing novel biomarkers and therapeutic targets for early cardiovascular disease identification and intervention. He has published over 350 peer-reviewed articles in high impact journals, and received numerous awards in recognition of his research and scientific accomplishments, including the Canadian Cardiovascular Society Research Achievement and Lifetime Achievement Awards.
Dr. Liu has chaired scientific sessions of the Canadian Cardiovascular Society, Heart Failure Society of America, the International Society of Heart Research and the Human Proteomic Organization, amongst others. Currently he is the Director of the National C-CHANGE Initiative, harmonizing and integrating cardiovascular preventive guidelines for both professionals and patients, and developing strategies for implementation. The harmonized Canadian C-CHANGE guidelines have recently been chosen by the provincial premiers in Canada as the first chronic disease guideline to be mandated by the Ministries of Health across the entire country. He is also President of the International Society of Heart Failure of the World Heart Federation (WHF), and also serves on the Research and Policy Committees of the World Heart Federation, coordinating the global fight against heart disease and promoting its prevention.
Novel Innate Immune Regulators of Cardiac Remodeling post MI
Inflammation underlies many forms of chronic disease, and is often triggered following acute tissue injury. The recent recognition of general “danger associated molecular patterns” (DAMPs) released following tissue injury can rapidly activate host innate immune pathways, including that of the ubiquitous toll-like receptor (TLR), provided a potential rationale for the cardiac remodeling process following acute ischemic injury. Our previous work demonstrated that adaptors for TLR such as MyD88 and downstream signal amplifiers IRAK4 or IRF3 all contribute to excessive local cardiokine release, inflammatory cell mobilizatioin, matrix disoolution, cardiac dysfunction and high mortality. IRAK4 in particular accelerated apoptotic program and promoted dendritic cell mobilization, while IRF3 inhibited angiogenesis and accelerated autophagy and subsequent cell deaths.Down regulation of both is beneficial.
Searching for novel cardiac remodeling related innate immune regulatory factors that may serve as targets for therapy, we have recently identified Mindin, a member of F-spondin family and facilitator of bacterial opsonization, to be significantly up regulated following myocardial infarction (MI). Mindin is produced in myocytes following acute hypoxic or free radical injury, and enhances TLR4 signaling. Mindin-/- deficiency conferred major protection following acute MI in the murine model, with reduction in infarct size, cardiac volumes, cell deaths, fibrosis and improvements in EF. Mechanistic analysis suggested direct interaction of mindin with TLR4, and downstream signal transduction is markedly enhanced when mindin colocalizes with TLR4. Surprsingly, mindin is present in serum of patients with heart failure. Mindin may thus identify a population at risk for heart failure where mindin itself may serve as a target for therapy.
Accompanying this search, we also identified CARD11/Carma1,a sub- sarcolemmal scaffold protein integrating multiple stress signals including that downstream to TLR4, to be also up regulated following MI. Again CARD11 is induced following cardiac injury, and CARD11-/- deficiency conferred major protection post-MI. CARD11 appears to contribute to multiple signaling pathways to promote apoptosis, and may represent a companion target in the setting of cardiac remodeling post-MI.
Qingbo Xu, M.D.,Ph.D.
King’s College London, UK
Professor Xu qualified in Medicine in China and undertook postgraduate research training at Peking Union Medical College and then the University of Innsbruck Medical School in Austria. He was appointed Professor in Cardiovascular Science at St George’s Hospital in 2000 and then to the BHF John Parker Chair of Cardiovascular Sciences at King’s College London in 2006. He has a very prominent international profile in vascular biology as evidenced by numerous invited lectures at national and international scientific meetings, chairing of many research conferences, service on the editorial boards of eminent journals (e.g. Consulting Editor, ATVB), and membership of national and international committees. He edited the widely used guide ‘Handbook of Mouse Models of Cardiovascular Disease’. Professor Xu has been honored with the Austrian Cardinal Prize for Medicine in 1993, the Rokitansky Prize for Pathology in 1995, and several visiting professorships. His major research interesting is in the field of vascular repair. Professor Xu has made the important finding on the presence of stem/progenitor cells in the adventitia of the vessel wall that have the ability to differentiate into endothelial or smooth muscle cells. Professor Xu has also introduced several innovative experimental techniques to research in the above areas. One was establishing the first mouse model of vein bypass graft atherosclerosis in 1998, which is now widely used internationally and has proven to be a powerful tool for mechanistic studies and drug screening. Another technical innovation was the partial mapping of the proteomes of vascular and stem cells. Professor Xu’s original work has contributed to atherosclerosis research as indicated by his publication list that includes many highly cited papers (H-index 61).
An Update on Vascular Stem Cells in Arteriosclerosis
It is established that mature endothelial cells can proliferate and replace damaged cells in the vessel wall. However, recent findings indicate an impact of stem and progenitor cells in repair process of the vessel wall. And also stem cells can differentiate into smooth muscle cells (SMCs) that may be participate in the development of arteriosclerosis. This presentation aims to briefly summarize the recent findings in stem cell research relating to the role of the cells in vascular diseases. It has been demonstrated that stem cells present in the blood may be derived from a variety of sources, including bone marrow, spleen, liver, fat tissues and the adventitia of the arterial wall. In response to cytokine released from damaged vessel wall and adhered platelets, circulating stem cells home to the damaged areas. Recently, we demonstrated that “classic endothelial progenitor cells” (EPCs) were actually monocytes/macrophages that taken up micro-particles released from the platelets, indicating EPCs in circulation are rare in number. On the other hand, accumulating evidence supports the existence of vascular stem cells in the vessel wall. In the adventitia, abundant vascular progenitors (Sca-1+) were found, which actively participate in the pathogenesis of vascular disease via differentiation into endothelial and smooth muscle cells. To explore therapeutic possibility, Sca1+ cells were applied locally. While the injured vessel was completely occluded by arteriosclerotic lesions 2 weeks postoperatively, local transfer of shear stress-induced Sca1+ cells significantly reduced neointima lesions. Thus, stem cells contribute to vascular repair, during which shear stress promotes stem cell differentiation towards endothelial phenotypes. Concerning SMCs, it has been demonstrated that stem/progenitor cells might also accumulate in the intima where they differentiate into SMCs, especially stem cells in the vessel wall. However, several issues concerning the contribution of bone marrow stem cells to the pathogenesis of vascular disease are controversial, e.g. whether bone marrow-derived stem cells can differentiate into SMCs that form neointimal lesions of the vessel wall. The aim of this presentation is to update the progress on the role of stem cells in arteriosclerosis, to discuss the mechanisms of stem cell homing and differentiation into mature endothelial cells and SMCs and to highlight the controversial issues in the field.
Yibin Wang ,Ph.D.
The University of California,Los Angeles, USA
Dr. Wang obtained his training in molecular genetics and cell biology from Baylor College of Medicine, and conducted post-doctoral research in neurobiology and cardiovascular diseases at The Scripps Research Institute and UC, San Diego.
Dr. Wang is the Professor of the Department of Anesthesiology, Physiology and Medicine at the University of California, Los Angeles. He is the Director of Division of Molecular Medicine and the Vice Chair of Department of Anesthesiology at UCLA. He has been the “Changjiang Scholar” at Shanghai Jiaotong University since 2009. Dr. Wang has chaired and co-chaired multiple international conferences including BCVS meeting of American Heart Association and ISHR international congress. Dr. Wang has been serving on the editorial boards of Circulation Research, JBC, JMCC, J Cardiac Failure. He has published more than 130 peer-reviewed research articles which have been cited more than 5000 times.
Dr. Wang’s laboratory has focused on molecular basis of stress-induced intracellular signaling pathways and their functional impact on cardiovascular physiology and diseases. Wang’s lab has developed a number of genetic models to achieve targeted manipulation of signaling molecules in intact animals. Dr. Wang has also demonstrated a particular strength in discovering novel components and novel interactions in stress-signal transduction pathways in mammalian cells through biochemical, proteomic, molecular and genomic approaches. Dr. Wang’s lab has established broad spectrum of research capacity in cardiovascular biology, from molecular biology, cell physiology to intact heart physiology and systems biology.
Novel Mechanisms in Cardiac Reprogramming in Heart Failure
Yibin Wang ,Ph.D.
The complexity of transcriptome and proteome is contributed by alternative splicing of mRNA. Altered mRNA splicing is also implicated in many human diseases. However, little knowledge is available about the scope of alternative splicing at whole genome level in heart diseases and even less about the mechanisms underlying the regulation of mRNA splicing in response to pathological injury in heart. Using deep RNA-seq, we have identified global alternative splicing events associated with pathological remodeling during heart failure, resembling the splicing profile observed in fetal heart. In order to explore the underlying mechanisms, the expression profiles of splicing regulators were examined in neonatal, normal adult, and failing adult hearts. Among them, Fox1 was identified to be significantly down-regulated in both failing and fetal hearts. Morpholino mediated Fox1 knock-down in zebrafish embryos led to lethal phenotype associated with impaired cardiomyocytes maturation and cardiac function. Interestingly, this phenotype could be rescued by re-expressing both zebrafish and mouse Fox1 gene. Using bioinformatic analysis and in vitro minigene reporter assay, we have identified Mef2a, a transcription factor with important impact on cardiac development and remodeling to be a direct downstream target of Fox1. Mef2a alternative splicing is dynamically regulated during both mouse and zebrafish cardiac development, and inhibition of Fox1 in zebrafish embryo also affected Mef2a splicing on the same exon. Overexpressing different Mef2a isoforms in zebrafish leads to different cardiac phenotypes, suggesting the functional significance of Mef2a alternative splicing. To our knowledge, this study provided the first comprehensive analysis of mRNA splicing regulation in heart, and identified Fox-1 as a potential key regulator for fetal-like RNA splicing switch during heart failure by targeting cardiac regulatory genes, including Mef2s. Establishing RNA splicing machinery in hearts adds important new insights to the complex regulatory network for cardiac transcriptome reprogramming during development and diseases.
15、 Biographical Sketch
University of Washington, USA
Personal Statement: I have been studying the molecular mechanisms regulating cardiac metabolism and energetics for nearly 20 years. A long-term goal of my laboratory is to understand the metabolic role in the pathogenesis of heart failure. We have utilized molecular and genetic approaches to identify and perturb specific regulators in the key pathways of cardiac energy metabolism in mice and subsequently interrogated the physiological and biochemical responses in vivo during the development of heart failure using multi-nuclear NMR spectroscopy. Our past work focused on the oxidative metabolism and mitochondrial ATP synthesis in heart failure using mouse models of altered glucose and fatty acid metabolism in the heart. We have also evaluated the role of mitochondrial biogenesis and mitochondrial DNA replication in the pathogenesis of heart failure in patients. Our recent work seeks to decipher the mechanistic link between impaired oxidative phosphorylation and mitochondria-trigger cell death during chronic stresses. Results of these studies strongly suggest that mitochondrial oxidative metabolism is a critical determinant of cardiac response to stress, and furthermore, the metabolic flexibility is essential for sustaining normal cardiac function. In our effort to investigate the signaling mechanisms regulating cardiac metabolism, we have focused AMP-activated protein kinase (AMPK) in the past 15 years. We are the first to show that AMPK is activated by impaired myocardial energy status in pathological hypertrophy. In a number of follow-up publications, we have demonstrated that AMPK is a critical and sensitive signaling intermediary linking cardiac energetics and metabolism, and activation of AMPK is cardioprotective during both acute and chronic stress conditions. Moreover, our AMPK research program has yielded multiple transgenic/ mutant mouse models with altered AMPK signaling cascade to dissect the isoform-specific function of the kinase complexes.
Mitochondrial dysfunction and heart failure
Mitochondrial dysfunction is linked to the pathogenesis of multiple diseases including heart failure but the specific mechanisms for this link remain largely elusive. Impaired energy supply due to defective oxidative metabolism, a higher oxidative stress and a greater mitochondria-trigger cell death are among the most commonly proposed mechanisms. In a mouse model of mitochondrial Complex I (C-I) deficiency in the heart we found that a significant decrease in the C-I supported respiration did not compromise normal cardiac function in vivo or high-energy phosphate content in isolated perfused hearts. However, these mice are more susceptible to stress, developed accelerated heart failure after pressure overload or repeated pregnancy. C-I deficiency caused accumulation of NADH and decreased NAD+/NADH ratio. As the result, Sirt3 activity was inhibited leading to increases in protein acetylation, and sensitization of the permeability transition in mitochondria (mPTP). Similar changes in the redox state and mitochondrial protein acetylation were also seen in other models of heart failure. Pharmacological treatment that restored the NAD+/NADH ratio normalized protein acetylation and mPTP sensitivity. These findings describe a mechanism connecting mitochondrial dysfunction to the susceptibility to diseases and propose a potential therapeutic target.
Chunxiang Zhang, M.D., Ph.D., FACC.
Chunxiang “Kevin” Zhang, MD, PhD, FACC. Dr. Zhang is an Endowed Chair Professor, the Chairman of the Department of Pharmacology and the Director of University Cardiovascular Research Center at Rush University in Chicago. He has over 20 years of experience and expertise in the areas of basic, translational and clinical cardiovascular research. During 2001-2006, he had set up and overseen a cross-department vascular injury laboratory at the University of Tennessee. From 2007-2010, Dr. Zhang had worked as the Vice Chairman for Research at New Jersey Medical School. Since 2011, He has moved to Rush University as the Chairman of the Pharmacology Department. Dr. Zhang’s research team is a pioneering group to explore the roles of miRNAs in cardiovascular biology and cardiovascular diseases. He has published over 70 peer-reviewed research articles in high impact journals such as Science, J Exp Med, Circ Res. ATVB, Diabetes, and JBC (h-index: 32; citations: 4008). His research achievement is also well-documented in his grant application. Since 2001, he has obtained nearly $15 million research grants from NIH, AHA and ADA. Dr. Zhang’s current research programs are focused on microRNAs and stem cells in atherosclerosis & restenosis, myocardial infarction, cardiac hypertrophy, cardiovascular aging and diabetic cardiovascular complications. In addition to research and research administration, Dr. Zhang is also highly active in other academic activities at both national and international levels. He is the Chair of the Events/Conference Committee for the International Society for Translational Medicine (ISTM). He is a Fellow of the American College of Cardiology, and a Councilor of the American College of Cardiology at Chicago. He is the Editor-in-Chief of American Journal of Contemporary Cardiovascular Research; Associate Editor of Journal of Translational Medicine; and Editorial Board member of 15 Peer-reviewed Journals. Dr. Zhang is also the grant reviewer for 11 national and international research organizations including NIH, VA system, Chang Jiang Scholars Program, and the National Natural Science Foundation.
MicroRNAs in Cardiovascular disease: current research progress and
MicroRNAs (miRNAs) are a novel class of endogenous, small, noncoding RNAs that regulate gene expression via degradation or translational inhibition of their target mRNAs. As a group, miRNAs are able to directly regulate at least 30% of genes in a cell. In addition, other genes may also be regulated indirectly by miRNAs. It is therefore not surprising that miRNAs could be the pivotal regulators in normal development, physiology, and pathology. Recent studies from us and other groups have demonstrated that miRNAs are highly expressed in cardiovascular system and their expression is dysregulated in diseased hearts and vessels. miRNAs are found to be critical modulators for cardiovascular cell functions such as cell differentiation, contraction, migration, proliferation, and apoptosis. Accordingly, miRNAs are involved in the many cardiovascular diseases such as cardiac hypertrophy and heart failure, atherosclerosis, ischemic heart disease, cardiac arrhythmias, angiogenesis, atherosclerosis and restenosis after angioplasty. Moreover, In contrast to our original thought, miRNAs exist in circulating blood and are relatively stable, thus, they could be proved useful as biomarkers for cardiovascular disease. miRNAs may play important roles in diagnosis, prevention and treatment of cardiovascular disease.
Jun Ren, Ph.D.
Wyoming University, USA
Dr. Ren earned his Ph.D. in 1994 from the University of Alberta, Canada, in the area of cellular physiology, following his medical training in China (Beijing University and Peking Union Medical College). In 1994, he became a post-doctoral fellow in the Wayne State University School of Medicine (Internal Medicine), where he served for two years. He remained at Wayne State University until 1998, working as a research instructor of physiology. He was an Assistant Professor of Physiology at the University of North Dakota School of Medicine and Health Sciences from 1998-2002 and then an Associate Professor of University of Wyoming from 2002-2005. He was promoted to full professor in 2005 and was appointed as Associate Dean for Research in the College of Health Sciences at the University of Wyoming. His major area of research is related to cardiac pathophysiology in alcoholism, diabetes, obesity and aging. His research has been funded by the American Heart Association, American Diabetes Association and NIH. He is a first or corresponding author of more than 300 peer-reviewed papers and 100 published abstracts. He is editor or on editorial board for a number of journals including Journal of Molecular and Cellular Cardiology, American Journal of Physiology, Cardiovascular Toxicology and Clinical and Experimental Pharmacology and Physiology.
Cardiac dysfunction and autophagy in obesity
Jun Ren, Ph.D.
Autophagy is an intracellular, lysosomal-dependent process involved in the turnover of long-lived proteins, damaged organelles, and other subcellular structures. The autophagic process is known to play an essential role in the maintenance of cellular homeostasis and results from recent studies also indicate an important role in the pathogenesis of human diseases including cancer, cardiovascular diseases, obesity, diabetes mellitus and aging. Because of the pivotal role of autophagy in the regulation of adipogenesis, obesity and insulin sensitization, research efforts have focused on elucidating the role of autophagy in metabolic syndrome. The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and is characterized by a complex signaling mechanism that affects protein synthesis and autophagy. Results from experimental and clinical studies reveal some interesting, but conflicting, findings regarding the mTOR signaling pathway and autophagy in adipocytes under metabolic syndrome.
Pin-Lan Li, M.D.,Ph.D.
Virginia Commonwealth University, USA
Personal Statement: The major research focus in my laboratory is on the regulation of coronary circulation in health and disease. Over the last 10 years, we have published more than 50 research articles in this field with major emphasis on functional regulation of coronary arterials cells and related signaling mechanisms. The project onCD38-ADP ribosylcyclase signaling has continued for more than 12 years and over the time period we demonstrated that two major products of this enzyme, namely, cADP-ribose and NAADP importantly contribute to the regulation of coronary vascular function. One of the most important findings in our laboratory is the NAADP regulation of lysosome function through lysosomal TRP-ML channels in arterial smooth muscle, which represents a unique and critical regulatory pathway for lysosome function and subsequent cell surviving, death and proliferation and vasomotor responses.
Now we attempt to extend our functional studies to disease models to address the pathological relevance of these signaling molecules, in particular, NAADP as a lysosome function controller. My laboratory is well equipped to use various state-of-the-art approaches to study coronary arterial cell signaling and related functions or pathophysiology including gene cloning and mutation and gene expression, ESR, LC/MS, membrane reconstitution, somatic gene or siRNA transfection, confocal microscopy, and fluorescent molecular imaging in vitro and in vivo. Over last 5 years, with the help of our animal resource center we maintained and generated several genetically engineered mouse colonies including CD38-/-, acid sphingomyelinase (ASM)-/-, gp91phox-/- and their wild type matches as well as double knockout colonies such as ASM-/-+gp91phox-/- and their variants. These mouse models, in particular, CD38-/- and CD38+/+ mouse model will be important for the proposed studies in this application. I am confident that with my extensive experience in the research area of coronary circulation and well-trained lab staff we are able to successfully accomplish all proposed studies in this application. To our knowledge, this laboratory is the only laboratory nationwide to focus on this important signaling pathway in the regulation of coronary circulation and in large the only research group in studying lysosome regulation of vascular cell autophagy in health and disease.
Lipid Raft-Redox Signaling Platforms: Implication for Endothelial
Dysfunction and Vascular Injury
Pin-Lan Li, M.D.,Ph.D.
Lipid rafts, the sphingolipid and cholesterol-enriched membrane microdomains, are able to form different membrane macrodomains or platforms upon stimulations, including redox signaling platforms, which serve as a critical signaling mechanism to mediate or regulate cellular activities or functions. In particular, this raft platform formation provides an important driving force for the assembling of NADPH oxidase subunits and the recruitment of other related receptors, effectors, and regulatory components, resulting, in turn, in the activation of NADPH oxidase and downstream redox regulation of cell functions. This comprehensive review attempts to summarize all basic and advanced information about the formation, regulation, and functions of lipid raft redox signaling platforms as well as their physiological and pathophysiological relevance. Several molecular mechanisms involving the formation of lipid raft redox signaling platforms and the related therapeutic strategies targeting them are discussed. It is hoped that all information and thoughts included in this review could provide more comprehensive insights into the understanding of lipid raft redox signaling, in particular, of their molecular mechanisms, spatial-temporal regulations, and physiological, pathophysiological relevances to human health and diseases
Xian Wang, Ph.D.
Peking University, China
Cheung Kong Professor in Physiology; Director of Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education; Vice President for Education of Peking University Health Science Center; Chinese Association for Physiological Sciences (CAPS) and Former Vice President of International Union of Physiological Sciences (IUPS).
Prof. Wang has been the recipient of many awards and honors during her career such as “Distinguished Young Investigator Award” honored by the National Natural Science Foundation of China, Leader of “Innovation Research Groups of NSFC” and so on. Over a decade, she has received more than 20 national research grants to support her research and published more than 170 scientific papers, 120 papers of which have been published in SCI journals, such as Circ Res, Diabetes, Am J Physiol and FASEB J. etc. Prof. Wang’s major research interest is related to the pathogenesis and prevention of metabolic vascular diseases.
Hyperhomocysteinemia-accelerated Insulin Resistance & Atherosclerosis-Role of Macrophages
Xian Wang, Ph.D.
Homocysteine (Hcy) is a sulfur-containing amino acid formed during the metabolism of methionine. Hyperhomocysteinemia (HHcy) has been implicated as an independent risk factor of atherosclerosis. We have showed that HHcy, as a potent pro- inflammatory factor, promotes insulin resistance in mice by inducing the expression and secretion of resistin, a pro-inflammatory adipokine from adipose tissue. In addition, Hcy-promoted macrophage infiltration aggravates ER stress in adipose tissue. HHcy inhibits insulin sensitivity in adipose tissue by inducing ER stress, activating JNK to promote pro-inflammatory cytokine production and facilitating macrophage infiltration. Previously, we have also showed that HHcy-accelerated atherosclerosis. Furthermore, HHcy greatly increased the incidence of Ang II–induced abdominal aortic aneurysm (AAA) and aortic dissection in ApoE-/- mice. Hcy sequentially stimulates adventitial fibroblasts transformation into myofibroblasts, secretion of IL-6 and MCP-1 and consequent recruitment of monocytes/macrophages to adventitial fibroblasts, which is abolished by the NADPH oxidase inhibitor DPI. NADPH oxidase 4 (Nox4). Folic acid supplement (0.071 g/g/day) markedly reduced HHcy aggravated Ang II–induced AAA formation in ApoE-/- mice. Finally, we have found that Hcy increases M1, but inhibits M2 macrophage polarization. These findings might reveal a central role of macrophages of HHcy in the pathogenesis of insulin resistance & Atherosclerosis.
Peking Union Medical College, China
Dongfeng Gu is Vice President and Deputy Director, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College. Dr. Gu is a professor with specialities in cardiovascular epidemiology and medical genetics at Peking Union Medical College (PUMC). He is a council member of the International Society of Cardiovascular Epidemiology and Prevention, and has served on the editorial boards of the Journal of Hypertension, and the Human Genetics. Publications include over 190 papers in peer-reviewed international medical journals. He has led large observational and interventional studies in both the epidemiology and medical genetics fields that have explored the causes or risk factors associated with hypertension, atherosclerosis and obesity, health burden and prevention of cardiovascular diseases in populations. He received his medical training and doctorate in Nanjing Medical University (1978-1983) and Peking Union Medical College (1986, 2007), and did his postdoctoral training in the United States (1990-1992) and the United Kingdom (2000). His main research interests include the identification of environmental and genetic risk factors or etiology of hypertension and coronary artery disease, and population-based approaches to prevention and control of cardiovascular diseases.
Genetic predisposition to Coronary Artery Disease in Chinese population
Coronary artery disease (CAD), and its most severe complication myocardial infarction (MI), are leading causes of death and disability worldwide. The disease is a result of dysfunctional systems involving many genetic and environmental factors as well as their interactions. Recent genome-wide association studies (GWAS) of CAD have discovered multiple chromosomal regions. However, most of the GWAS have focused on samples of European origin, and the identified loci altogether explain only a small fraction of the risk for CAD. Moreover, the variants identified in populations of European descent might not be applicable in other ethnic groups because of underlying genetic heterogeneity. We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease (CAD) comprising 1,515 CAD cases and 5,019 controls of Chinese Han descent, followed by genotyping top association signals in the replication stage (15,460 cases and 11,472 controls). We successfully identified four new loci for CAD (TTC32-WDR35 on 2p24.1, GUCY1A3 on 4q32.1, C6orf10-BTNL2 on 6p21.32, and ATP2B1 on 12q21.33) with genome-wide significance (P < 5 × 10-8). We also replicated four loci previously identified in European populations (PHACTR1 on 6p24.1, TCF21 on 6q23.2, CDKN2A/B on 9p21.3, and C12orf51 on 12q24.13) in addition to supporting evidence for other ten reported CAD loci. A CAD risk score was calculated to examine the effect of nine associated SNPs in aggregate on the risk for CAD. These findings provide new insights into biological pathways for the susceptibility of CAD in Chinese Han population.
Feng Gao, M.D., Ph.D., FAHA
Fourth Military Medical University, China
Dr. Feng Gao is a Professor of Physiology, Associate Dean of the School of Basic Medical Sciences at the Fourth Military Medical University, Xi’an China. He also holds positions as Adjunct Professor at Peking University. He received his MD and PhD of Phy- siology from the Fourth Military Medical University and had his postdoctoral training at Thomas Jefferson University in the USA. He has been engaged in the field of cardioprotection for many years. His found the cardioprotective effect of postconditioning for the ischemic/reperfused heart and proposed this concept in 1999. In recent years, he has devoted himself to the study on the role of insulin in cardiovascular health and disease and the underlying mechanisms of actions. He found that insulin exerts significant antiapoptotic and cardioprotective effects via activating PI3 kinase-Akt-eNOS-NO signaling mechanism. Based on these findings, they proposed the “insulin hypothesis” which highlighted insulin as the predominant protective component in the GIK cocktail. This insulin-induced “survival” signaling and resultant cardioprotection may represent a novel approach for the development of pharmacological strategies that prevent insulin resistance and diabetic cardiovascular diseases. Currently, his lab is studying the role of mitochondria in exercise-induced cardioprotection in diabetic cardiovascular diseases.
He is currently serving as an Associate Editor of Life Sciences, editorial board member of Cardiovasc Res and Apoptosis. He is a standing board member of the Scientific Advisory Board, International Academy of Cardiology and fellow of AHA.
Cardioprotective effect of insulin for the ischemic heart
Accumulating evidence has suggested that insulin signaling plays an important role in cardiovascular functioning, and failure of this in metabolic syndromes characterized by insulin resistance results in cardiovascular diseases. This presentation focuses on our recent findings that insulin, in addition to its metabolic modulation, exerts direct cardioprotective actions against myocardial ischemic injury via activating PI3 kinase-Akt-eNOS-NO “survival signaling” with nitric oxide as an “end effector”. Our findings also suggest the potential beneficial effects of glucose-insulin-potassium (GIK) cocktail, in which insulin acts as the key component, in acute organ protection (figure 1).
Lize Xiong, M.D.,Ph.D.
Fourth Military Medical University, China
Dr. Lize Xiong is currently the President of Xijing Hospital, the Fourth Military Medical University. He is also the Director of the Key Laboratory of the Critical Care Medicine of the PLA. As specially- appointed Professor for Chang Jiang Scholar by the National Ministry of Education, Dr.Xiong acts as an Executive Committee Member of World Federation of Societies of Anaesthesiologists (WFSA) and Secretary of Asian Australasian Regional Section (AARS) of WFSA, president-elected of Chinese Society of Anesthesiology (CSA) of Chinese Medical Association (CMA), vice-president of Chinese Society of Clinical Pharmacy of Chinese Medical Association (CMA).
Dr.Xiong graduated from The Fourth Military Medical University in 1985 and received ICU training in Peking Union Medical College hospital in Beijing. For further research experiences, he went to Nuffield Department of Anaesthetics, Oxford University, England in 1992 and. Yamaguchi University School of Medicine, Japan in 1998 as Visiting Scholar.
Dr.Xiong’s research interest is neuroprotection, he was awarded the First Class of the State Science and Technology Prizes in 2011, and his research supported by 18 key projects, as Majors Program of National Natural Science Foundation of China, National Natural Science Founds for Distinguished Young Scholar, and Joint Research Fund for Overseas Chinese Young Scholars, etc. Currently, he has got 3 First Class Science &Technology of Shaanxi Province and 9 National Patents. Dr.Xiong was invited to deliver speeches at many International Conferences and has published more than 123 peer-reviewed papers and 24 chapters. He serves as associate chief editors and board members for a number of academic journals.
The translational study of preconditioning for cardiac surgery
Lize Xiong, M.D.,Ph.D.
The prevalence of cardiac disease is increasing each year, resulted in an elevating quantity of surgical patients with cardiac comorbidities. It is a crucial and difficult subject in medical research of how to ensure the perioperative safety of this kind of patients. We carried out several translational studies on non-ischemic preconditioning strategies. And found that hyperbaric oxygen preconditioning as well as electro- acupuncture preconditioning can significantly reduce myocardial damage in heart surgery patients, which is helpful for patients’ recovery. This report will mainly focus on introducing our recent RCT trials carried out in single or multiple clinical centers.
Third Military Medical University, China
Zhu Zhiming, MD, Professor of Cardiovascular Medi- cine and Metabolism Director of Center for Hyper- tension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, China
Dr. Zhu received his medical degree in 1985 and Master of Science in Cardiology from the Third Military Medical University, Chongqing in 1988 and obtained his MD from Muenster University, Germany in 1993. He received postdoctoral training and as a research associate at Department of Cell Biology and Physiology in University of North Carolina at Chapel Hill from 1994-1997. He is a visiting professor in Riley Heart Research Center at School of Medicine in Indiana University-Purdue University Indianapolis from April to November, 2002.
Dr. Zhu’s research interests focus on: mechanism and treatment of hypertension and metabolic syndrome. Of special interest is the role of transient receptor potential (TRP) channels in the pathogenesis of cardiometabolic diseases. He has published over 70 peer-reviewed articles such as Cell Metabolism, Circ Res, Arterio Thromb Vasc Biol, Hypertension, Stroke, Diabetes, et al. He is a Fellow of American Heart Association. He was awarded as Changjiang Scholar and National Science Foundation for Distinguished Young Scholar of China. He serves on the Editorial Board of Clinical Science, Pflugers Archiv, Hypertension Research, Clin Exp Physiol Pharmaco and on more than ten editorial boards of Chinese professional journals, such as Chin J Hypertension (associate editor).
Chilli pepper and spicy TRPV1 in the cardiometabolic protection
Cardiometabolic disease remains one of leading causes of morbidity and mortality throughout the world. Therapeutic lifestyle changes can prevent cardiometabolic lesions. Transient receptor potential vanilloid type-1 channel (TRPV1) is a non-selective cation channel that can be specifically activated by capsaicin, a major pungent ingredient in chili pepper. Although capsaicin has several biological effects on the sensory nerves, the long-term effect of capsaicin on cardiometabolic regulations is not well-known. In the past ten year, our studies show that TRPV1 is widely expressed in cardiometabolic organs and has multiple cardiometabolic regulatory effects to capsaicin stimulation. To further understand the link between TRPV1 and cardiometabolic diseases, we investigated the effects of dietary chili pepper and spicy TRPV1 on several cardiometaboic diseases, such as hypertension, diabetes, obesity, and atherosclerosis, and so on. Our studies provide new insights into the involvement of TRPV1 channels in the pathogenesis of cardiometabolic disorders and implicate this channel as a potential therapeutic target for the management of cardiometabolic diseases.
Wei Kong ,Ph.D.
Peking University, China
WEI KONG, MD, Ph.D., professor in the Department of Physiology and Pathophysiology, Peking University Health Science Center.
Research interest: Extracellular matrix remodeling and the pathogenesis of cardiovascular disease. She has published more than 30 papers in peer-reviewed scientific journals such as Circ Res, ATVB, Faseb J et al.
Award: China National Funds for Distinguished Young Scientists (2012); New Century Excellent Talents in University, Ministry of Education (2007)Editorial board member of “Curr Vasc Pharmacol”. Board member of the International Matrix Biology Association.
In the past 5 years as a Project Leader presided over 10 funds including the National Natural Science Foundation of International Cooperation, Ministry of Science and Technology "973" projects etc.
Extracellular Matrix and Cardiovascular Remodeling
Wei Kong ,Ph.D.
Cardiovascular remodeling, defined as any enduring change in the size and/or composition of an adult heart or blood vessel, underlines the pathogenesis of major cardiovascular diseases. Cumulative studies have demonstrated that extracellular matrix (ECM) turnover play a critical role during cardiovascular remodeling. My lab has been focused on a 524-kDa matricellular glycoprotein, cartilage oligomeric matrix protein (COMP) in cardiovascular system. COMP belongs to the thrombonspondin (TSP) family and is also named TSP-5. Increasing interest on TSP-1,2,4 has emerged and they have been studied in angiogenesis, atherosclerosis, cardiac hypertrophy, myocardial infarction, heart failure etc. However, there is very little knowledge of TSP-3 and TSP-5 in cardiovascular system. Our study indicates that COMP is pivotal for maintaining the homeostasis of VSMCs in both vessels and heart. Manipulation of COMP level (synthesis and degradation) may shed light on the prevention and treatment of a variety of cardiovascular diseases.
Shanghai Jiaotong University,China
Dr Gao is the Chief of the Department of Hypertension at Ruijin Hospital Jiaotong University School of Medicine, the Vice Director of Shanghai Institute of Hypertension, and Director of Shanghai Key Labo- ratory of Vascular Biology in Shanghai.
Dr Gao’s main research interests are: (1) diagnosis and therapy of resistant hypertension, including screening for secondary hypertension; (2) the establishment and application of genetic hypertension resources ( Dr Gao’s team has collected many samples, including hypertensive patients, normotensive subjects, nuclear families and sib-pairs); (3) the mechanisms of vascular remodeling in hypertension, her main focus being the evaluation of vascular adventitial structure and function induced by inflammation in vascular injury; (4) screening and discovery of new biomarkers in vascular injury. She is also the Director of the Center for Detection of Vascular Function at Shanghai Institute of Hypertension.
The role of vascular inflammation in vascular injury
OBJECTIVE: The vascular adventitia has long been considered a supporting tissue, the main function of which is to provide adequate nourishment to the muscle layers of tunica media. Over the last few years, it has been demonstrated that fibroblasts from the adventitia have been suggested to be involved in the local release of vasoactive compounds in vascular remodeling. In this study, we sought to determine whether the role of adventitia in vascular inflammation contributing to vascular injury. METHODS AND RESULTS: Animal models of balloon injury in carotid arteries and deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats were used in this study. Our results showed that angiotensin II and aldosterone increased OPN expression in adventitial fibroblasts in a time- and concentration-dependent manner. MAPKs and AP-1 pathways were involved in OPN upregulation. Perivascular delivery of antisense oligonucleotide for OPN suppressed neointimal formation post-injury. Similarly, VEGF increased OPN expression which mediated macro- phages chemotaxis. Furthermore, the inhibition of neointima formation was preceded by significant reduction of VEGF and OPN expression with concurrent macrophage infiltration into adventitia after injury. Perivascular adipose tissue also play an important role in vascular injury. We demonstrated PVAT-derived C3 stimulated AF migration and differentiation which were mediated by the c-Jun N-terminal kinase pathway. By using DOCA-salt hypertensive rats, we found morphological changes in perivascular adipocytes and increased expression of C3 in PVAT that was tightly associated with adventitial thickening and myofibroblast clustering around PVAT. CONCLUSIONS: These results demonstrate that adventitia, especially adventitial fibroblast and perivascular adipose tissue, by secreting inflammatory factors participates in vascular inflammation play an essencial role in vascular injury.
Peking Union Medical College, China
Professor of Medicine & Molecular Genetics State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China principal research interests：Cardiovascular Genetics, genomics and epigenetics, mainly focus on high blood pressure, atherosclerosis and cardiomyopathy
Dr.Hui got his PhD from University of Montreal, Canada. Subsequently, he was trained as a postdoc fellow in NIH. From1997, as the director of Sino-German Laboratory for Molecular Medicine in Fuwai Hospital, he focused on clinical cardiovascular genetics. Recently,Dr. Hui’s group determined several novel genes involved in cardiovascular disease (MCR2005, Circ. Res 2010, Hum Mol Genet 2010), firstly reported thede novoframeshiftmutation of theγ-subunit causing Liddle syndrome(ClinEndocrinol 2007), and the mutations in NEXN involved in the pathogenesis of HCM(Am J Hum Genet 2010), and firstly demonstrated the link between vitamin K and arterial vascular wall by VKORC1 (Circulation 2006, Cir: Cardiovasc Genet 2013, Hum Genet 2013). And also, his group did lots work in cardiovascular disease susceptibility genes (JACC 2007, Hypertension 2009, Stroke 2005&2009&2011&2012) and pathology of atherosclerosis (ATVB 2013). Dr. Fan serves as an ISHRpresident in China, and Editor in Chief of Molecular Cardiology of China, and the vice director of the State Key Laboratory of Cardiovascular Disease.
Monogenic diseases are much complex than thought
The prevalence of hypertrophic cardiomyopathy (HCM) is 1/500 and the clinical phenotype and prognosis of HCM have been noticed very heterogeneous. Pathologic characteristics of hypertrophic cardiomypathy（HCM） are cardiac myocyte hyper- trophy, ventricular cavity reduction, myocyte disarray, fibrosis with normal clinical presentation or diastolic heart failure as well as sudden cardiac death. It has been reported that 50%-70% of HCM are caused by mutations of genes encoding sarcomeric proteins. Most mutations are private ones. Clinical phenotypes of HCM are extremely heterogeneous. Those heterogeneous clinical phenotypes have been attributed to either malignant or benign mutations, or modifier genes or even environmental factors. We recently found that some pedigrees of HCM carried multiple mutations within one gene or in two more disease causing genes. The patterns of inheritance can be dominant or recessive. These may also contribute to the diversity of HCM clinical phenotype and expressitivity penetrance.
27、 Biographical Sketch
Xiaoli Tian, Ph.D.
Peking University, China
Xiao-Li Tian, Ph.D. Professor and Principal Investigator of Human Population Genetics, IMM (Institute of Molecular Medicine), Peking University, received his Ph.D. from Free University of Berlin, Berlin, Germany and trained as post-doctorate in Cleveland Clinic Foundation, where he identified a novel angiogenic factor AGGF1 by genetic approaches and became Staff Research Associate. In year 2006, he started to set up lab for human population genetics, searching for genetic components critical for cardiovascular aging process and related diseases by population-based genetic study and engineered animal models. Non-lipid associated atherosclerosis is one of the focus as well. At Peking University, he built the Multi-Centered Biobank of PKU (MCBP), recruiting about 170K blood samples from 5 large centers consisting of more than 17 qualified hospitals. He has two large cohorts of natural population localized in Middle West and southeast of China, consisting of 200k and 500k participants, respectively. Additionally, he also has more than 4000 centenarians in MCBP. The GWAS on coronary artery diseases has been completed and the functional characterization is undergoing. He recently became Chief Scientist of National Basic Research Program on “Molecular Basis of vascular aging and age-related cardiovascular diseases”.
AGGF1 triggers a novel pathway for endothelial cell survival independent
Endothelial cell (EC) viability is crucial to preserve endothelial integrity and physiological functions. AGGF1 is a newly identified angiogenic factor. Distinct from other angiogenic factors, AGGF1 harbors FHA and G-patch functional domains. The functions and associated signaling pathway remains largely unknown. Here, we demonstrate AGGF1 as a strong EC anti-apoptotic factor and identify an early activated signaling axis, AGGF1-mTORC2, which is required for EC survival in response to various pathological stimuli. AGGF1 acts as a transcriptional regulator for RICTOR, a key component of mTORC2 complex, to promote its expression. Intact mTORC2 phosphorylates and activates AKT, leading to activation of FOXO1 and transcriptional repression of Bim, a potent pro-apoptotic factor. AGGF1-mTORC2- mediated EC survival is isolated from the PI3K-dependent or MAPK-associated survival pathways. The forkhead-associated domain in AGGF1 is required and sufficient for its nuclear localization and for the activation of this anti-apoptotic pathway. Thus, we defined a new signaling pathway for EC survival — AGGF1-mTORC2, which may present novel therapeutic targets for improved endothelial integrity in vascular diseases.
Huazhong University of Science and Technology,China
Prof. Kai Huang: Vice President for Union Hospital, Huazhong University of Science and Technology (HUST); Director of Clinical Center for Human Genomic Research, Union Hospital, HUST; Professor in Department of Cardiovascular Diseases, Union Hospital, HUST. Prof. Huang engages in research field of molecular cardiology. His main research interest is the transcriptional regulatory mechanisms of cardiovascular and metabolic diseases. He has received about 20 research projects from the National Natural Science Foundation, the Provincial Natural Science Fund and other scientific and technological programs to support his research. Prof. Huang has published more than 40 scientific papers, most of which have been published in SCI journals.
PARP1 is a key regulator of estrogen receptor alpha dependent gene transcription
Activation of nuclear receptor estrogen receptor α (ERα) exerts cardiovascular protective effects by modulating the expression of ERα target genes. However, the underlying mechanism remains unclear. Poly(ADP-ribose) polymerase 1 (PARP 1), a ubiquitous multifunctional nuclear enzyme, participates in the processes of DNA repair, replication, modulation of chromatin structure, and transcriptional regulation. We examined the interplay between PARP1 and ERα, and identified PARP1 as an important regulator of ERα-dependent transcription. We showed that PARP1 could directly bind to and poly(ADP-ribosyl)ate ERα, Poly(ADP-ribosyl)ation increased ERα binding to estrogen response element (ERE) present in the promoter of target genes, and promoted ERα-mediated gene transcription. Estradiol, the ligand of ERα, increased PARP enzymatic activity and enhanced poly(ADP-ribosyl)ation of ERα. Upon treatment with estradiol, ERα binding to ERE and ERα dependant gene expression were dramatically increased in cultured vascular smooth muscle cells (VSMCs). Inhibition of PARP1 by PARP inhibitor or PARP1 siRNA decreased ERα binding to ERE, and prevented ERα dependent gene transcription in VSMCs. Further studies revealed that PARP1 served as an indispensible component for the formation of ERα-ERE complex by directly interacting with ERα. Thus, our results identify PARP1 as a key regulator of ERα in controlling ERα transactivation.
Yi Zhu ,M.D.
Tianjin Medical University,China
Yi Zhu received his M.D. from Xi'an Medical University and University of Lausanne, Lausanne, Switzerland. He completed his postdoctoral training at the Department of Experimental Pathology, New York Medical College on Dec.1995 and Division of Bio- medical Sciences, University of California, Riverside on Dec.1997. He worked as an assistant researcher and associate researcher at the University of California, Riverside from Jan. 1998 – Dec. 2007.
Yi Zhu has been the Professor and Vice Chair of Department of Physiology and Pathophysiology, Peking University, Health Science Center from 2003 and Associate Director of Peking University Diabetes Center from 2004. He has been the Vice President of Tianjin Medical University from 2012 and the Professor of Department of Physiology and Pathophysiology. He is the Associate Editor of Frontiers in Vascular Physiology and Editor of Arteriosclerosis Thrombosis and Vascular Biology; Journal of Diabetes; Chinese Journal of Pathophysiology; Progress in Physiological Sciences.
Yi Zhu engages in research field of Endothelial biology and physiology, including signal transduction in vascular endothelial cells and mechanism of atherosclerosis; the relationship between dyslipidemia and type II diabetes. He has published more than 80 SCI research articles.
Peking University, China
Dr. Zhang obtained her B.S. in Medicine in 1982 and Ph.D. at Xinjiang Medical University and Nihon University in 1992. She worked in Institute of Vascular Medicine at Peking University Third Hospital as a post-doctoral fellow between 1992 and 1994. She worked as a Post doctoral at the Department of Pharmacology, Emory University, USA from 1999 to 2001. Dr. Zhang has been a professor and an associate director of Institute of Vascular Medicine since 2002, an associate director of Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education since 2003, an associate director of Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health since 2011 and a director of Beijing Key Laboratory of Cardiovascular Receptors Research since 2012. As a principle investigator, she was in charge of more than ten grants including ‘973’ major grant from Ministry of Science and Technology, and grants from the Natural Science Foundation of China. She has published 200 research articles, 111 of which were in international journals.
Research Interests: Since 1993, her research has been focused on adrenoceptors and cardiovascular disease, especially on distribution, expression, mediated biological function, signal transduction, regulation, cross-talk between adrenoceptors, and pathophysiological alterations of adrenoceptors in heart and blood vessels. Recently she started to work on study of the signaling of the cardiac adrenoceptors in heart remodeling and heart failure as well as single molecular imaging detection in living cells.
Dr. Ming Xu, as a
Professor, now is working at Institute of Vascular Medicine, Department of
Cardiology, Peking University Third Hospital. He is a committee member of
International Society for Heart Research (ISHR) Chinese Section and
Cardiovascular Professional Committee of China’s Society of Pathophysiology. As
the principle investigator, he has been carrying several projects, including
national science foundation, Program for New Century Excellent Talents in
University and “985” grant for translational research (cooperated with Dr.
Cristen Willer from University of Michigan) and multi-displinary research.
Guoqing Liu, Ph.D.
Peking University, China
Professor George Liu, Institute of Cardiovascular Sciences, Peking University Health Science Center.
George Liu obtained his Ph.D. in Medical and Physiological Chemistry from University of Umeå, Sweden. He then had his postdoctoral training in molecular biology in University of California at Los Angeles and in medical genetics at University of British Columbia, Canada. He is now professor and deputy director in the Institute of Cardiovascular Sciences, Peking University. His major research interests are in lipid metabolism and atherosclerosis. Particularly, he developed various gene-modified animal models to investigate the relationship between hypertriglyceridemia and atherosclerosis, diabetes, obesity and neurological diseases. His recent works have been published in Circulation Research, ATVB, Atherosclerosis, Human Molecular Genetics, J Neuroscience and Gut, etc.
Yunzeng Zou ,M.D.,Ph.D.
Fudan University, China
Yunzeng Zou received his M.D. and Ph.D. from Beijing Medical College, China on July 1984 and the University of Tokyo Graduate School of Medicine, Japan on April 1997, respectively. He completed his postdoctoral training at the Department of Cardiovascular Medicine, the University of Tokyo Graduate School of Medicine on March 2000. He worked as a senior research scientist and group leader at the Department of Cardiovascular Medicine, the University of Tokyo Graduate School of Medicine from April 2000 to Feb 2001 and the Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Japan form March 2001 to Aug 2004, respectively.
Dr. Yunzeng Zou has been the Co-Chairman, Director of Research Center of Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China. He is also the PI of the Research Center for Cardiovascular Diseases, Institute of Biomedical Sciences, Fudan University.
Dr, Yunzeng Zou has been the recipient of many awards and honors during his career such as Young Investigators Award of Japanese Heart Failure Society, Hypertension Research-Novartis Award of Japanese Society of Hypertension, Chung Kong Professor of Chung Kong Scholars Program and National Science Fund for Distinguished Young Scholars by the National Natural Science Foundation of China. He has longstanding research interest in understanding the mechanism of hypertension, cardiac hypertrophy, and heart failure and Cell Therapy for Myocardial Infarction and Heart Failure. He has published more than 100 peer-reviewed research articles in SCI journals such as Nature, Nat Med, Nat Cell Biol, Circulation, Circ Res, J Clin Invest, Hypertension, Cardiovasc Res, JMCC, etc.
Zhi-Ren Zhang, M.D.,Ph.D.
Harbin Medical University,China
Zhi-Ren Zhang received his M.D. and Ph.D. from Harbin Medical University and SemmelweisUniversity
,respectively. He completed his postdoctoral training at the Department of Physiology School of Medicine, Emory University on Dec. 30, 2000. He worked as a senior scientist at the School of Biology, Georgia Institute of Technology from Jan 1, 2001 – June 30, 2005. He was appointed as a Tenure Track Assistant Professor at the Department of Medicine, Medical University of South Carolina on July 2005.
Zhi-Ren Zhang has been the Dean of Institute of Clinical Pharmacology at Harbin Medical University, the Chair of Dept. of Clinical Pharmacy and the Co-Chair of Department of Cardiology at the 2nd Affiliated Hospital of Harbin Medical University. He is also the Co-Director of Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, at Harbin Medical University.
Zhi-Ren Zhang has longstanding research interest in understanding the mechanism and regulation of ion channels and transporters, and how these processes are affected in human diseases, such as hypertension and arrhythmia. He has published more than 40 peer-reviewed research articles.
Hong-Bo Xin, Ph.D.
Vice president of Nanchang University and Dean of Nanchang University School of Medicine in China. He received his Ph.D in Pharmacology from Beijing Medical University in 1991. He had been working at Vanderbilt University, University of Pennsylvania and Cornell University in USA from 1993-2006 as a research associate or research assistant professor or assistant professor, respectively. From 2006-2009, he had been a professor in the National Key Laboratories for Biotherapy at Sichuan University and now he is a professor in the Institute of Translational Medicine at Nanchang University (ITMNU). So far, he has published nearly 60 research papers in the peer-reviewed journals including Nature, ATVB, JBC, NAR and so on. His research focuses on cardiovascular research, especially, in understanding the nature of the modulation of Ca2+ release from the ryanodine receptors (RyRs)/intracellular Ca2+ release channels (ICRCs) in heart by FK506 binding protein 12.6 (FKBP12.6) using genetically engineered animals models including gene targeting and transgenic mice. He is also interested in the development of biotechnologies for defining gene functions in which he has developed a high throughput technology for generating conditional knockout mice using engineered vectors that combine gene trapping, gene targeting and site-specific recombination techniques. Recently, he is also pursuing bio-pharmaceutics research and translational research in his lab at ITMNU.
Xi-Yong YU, M.D., Ph.D.
Guangdong General Hospital,China
Professor Yu engages in research field of molecular cardiology and pharmacology. His main research interests include chronic heart failure and diabetic cardiomyopathy. There were three research aspects: (1) gene therapy and stem cell therapy in heart repair; (2) the role of pro-inflammatory cytokines the develop- ment of cardiovascular disease; (3) epigenetics and pharmacogenomics in cardiology.
There were more than 400 papers published in the home and abroad academic journals (including 80 SCI papers), 8 books issued, and 9 National invention patents gotten. He has undertaken more than 20 research projects from the National Natural Science Foundation, the National Key Program of Basic Science, the Provincial Natural Science Fund and other scientific and technological programs. Professor Yu won 5 Medical and Health Progress Awards, and 3 Science and Technology Awards from Guangdong Provincial Government. He has also been awarded one of the academic and technology leaders of medical science and education project in Guangdong Province, the national outstanding young experts in Chinese and Western integrative medicine, the title of Glaxo Award for outstanding young doctors, the Ten Outstanding Young Persons in Guangdong Province Nomination Award, the State Department experts in special government allowances, the Guangdong provincial authorities forefront positions.
Xiang Gao Received his M.D. and Ph.D from Nanjing University and Thomas Jefferson University, respectively. He completed his postdoctoral training at Thomas Jefferson University on Dec.1995 and The Jackson Laboratory on Dec.1998. He worked as research associate at the Neuroscience Center, University of North Carolina at Chapel Hill from 1998-2000.
Xiang Gao has been the Professor of Inst. of Molecular Medicine, Nanjing University from 2000-2001 and MOE Cheung Kong Scholar from 2001.He has been the Director of Model Animal Research Center of Nanjing University from 2002-2012 and the Director of National Resource Center for Mutant Mice from 2004. He has been the Associate Dean of School of Medicine of Nanjing University. He is the Director of Nanjing Biomedical Research Institute of Nanjing University. He is also the Member of Sreering Committee for International Mouse Phenotyping Consortium and President of Asia Mouse Mutagenesis and Resource Society and Editorial of Genesis, Science in China, Journal of Human Genetics.
The broad biological question his laboratory wishes to answer is the molecular mechanisms for controlling physiological homeostasis, as well as the causes for deleterious diseases related to such mechanisms. His Laboratory has published more than 120 research papers in SCI enlisted journals.
Nanjing Medical University,China
Professor Ji Yong was conferred the medical degree in 1991 and the Ph.D degree of cardiovascular pharmacology in 1998, Nanjing Medical University. Granted by French Ministry of Science, Ji did his postdoctoral research in French national health and Medical Research Institute (INSERM U464) and Universite De La Mediterranee, Marseille, France, focusing on protein/protein interaction. Then granted by Welcome Trust funding, Ji worked as a research fellow in King’s College London in UK, mainly studying the mechanism of eNOS in atherosclerosis, the vascular endothelium and platelet dysfunction in type 2 diabetes.
Professor Ji went back to China in 2004 and served as a professor in Department of Pathology and Pathophysiology, Atherosclerosis Research Center and Jiangsu Key Laboratory of Cardiovascular Molecular Intervention in Nanjing Medical University. The research team led by Yong Ji mainly works on nitric oxide and hydrogen sulfide, especially their effect on various cardiovascular diseases, such as myocardial ischemia-reperfusion injury, myocardial hypertrophy and atherosclerosis, as well as their mechanisms. The molecular mechanisms of drug prevention and treatment for those diseases have also been studied.
Professor JI has taken charge of multiple research projects, including Beforehand Research Project of National Key Basic Research Program of China (973 Program), Project of the State Key Program of National Natural Science Foundation of China, Projects of National Natural Science Foundation of China and the Wellcome Trust. The research team has published 37 research papers on international academic publications, such as Proc Natl Acad Sci USA, Cardiovasc Res, J Mol Cell Cardiol, Br J Pharmacol, etc.
Professor Ji serves as the vice chairman of the professional committee of athersclerosis of Chinese Association of Pathophysiology, member of professional committee of lipid and lipoprotein and the vice chairman of the youth professional committee of lipid and lipoprotein of Chinese Association of Biochemistry and Molecular Biology, vice chairman of youth professional committee of cardiovascular academy of Chinese Association of Pathophysiology, and the editor of British Journal of Pharmacology.
Qun-Sheng Ji, M.D., Ph.D.
AstraZeneca Innovation Center China
Qun-sheng Ji, Director & Head of Bioscience at AstraZeneca (AZ) Innovation Center China (ICC), is one of the pioneers who has contributed to shaping and expanding ICC since 2007. Now he is leading ~50 prominent scientists of Project lead, Assay development/HTS, In vitro Cell Science, In vivo Pharmacology, Genetics, Informatics, Biostatistics and Vivuriam facility for drug discovery in both oncology and kidney disease areas since 2011. Prior to this role, Dr. Ji was Director of Discovery Medicine (Translational Science), leading translational science support to AZ global oncology portfolio. In this role, he worked globally across AZ oncology research sites in UK & US to review global portfolio and prioritize translational science support accordingly. During this period, he also led efforts to reshape AZ translational science strategy and established scientific capabilities excellent in China, especially the molecular diagnosis (mutations detection & FISH) and patient derived tumor xenograft models. Before joined AstraZeneca, he had a 10-year industry experience in oncology drug discovery by leading a number of drug discovery projects in the US, including Onyx pharmaceuticals and OSI pharmaceuticals. OSI-906 (Linsitinib), an IGF-1R small molecule inhibitor currently in phase-2/3 trials in US, was discovered and developed under his leadership. He received his Ph.D. from Peking Union Medical College/Chinese Academy of Medical Science and Vanderbilt University in US in 1995, and MD from First Military Medical University in China in 1986. He is a co-author of 30 scientific papers. Dr. Ji is a funding member of Sino Drug Discovery Association (SDDA).
Hui-Hua Li, M.D.,Ph.D.
Capital medical University,China
Dr. Hui-Hua Li, male, born in October 1965. Yangtze River Scholar Distinguished Professor, Department of Pathology and Pathophysiology in Capital medical University. Winner of the National Science Foundation for Outstanding Young Scientists of China. He received his MD from Peking Union Medical College in Pathology and currently serves as vice Dean of Department of Pathology. His major research covers the ubiquitin-proteasome system and the molecular pathophysiological mecha- nisms of coronary heart disease, hypertension and heart failure, etc. He has published 43 research papers on JCI, PNAS, etc, that are cited over 1300 times in the past several years.
Youming Lu, M.D., Ph.D.
Huazhong University of Science and Technology,China
Youming Lu is the National Endowed Professor at Huazhong University of Sciences and Technology, Tongji Medical College, Wuhan, China and also the Bollinger Professor at Neuroscience Center, Louisiana State University School of Medicine, New Orleans. USA.
Dr.Lu graduated from the University of Toronto Faculty of Medicine. He pursued post-doctoral fellowships in Neuroscience at the Columbia University, New York. After his postdoctoral fellow, he was appointed as an tenure-track assistant professor at the Department of Physiology and Biophysics, University of Calgary, Calgary, Canada, and tenured associate professor at the Biomedical Science Center, University of Florida, and Bollinger professor at the Neuroscience Center, Louisiana State University School of Medicine, New Orleans. Since 2010, he has been appointed an the National Endowed Professor through 1000-plan program at the Huazhong University of Sciences and Technology.
His research focuses on synaptic transmission, plasticity and degeneration in some neurological disorders including stroke. In his early studies, he identified Src as a critical kinase in regulation of NMDA receptor channels and demonstrated a crucial role of this regulation if synaptic plasticity and learning (Lu et al., Science, 1998, and Lu et al., Neuron, 2000). Following these findings, he studied the cellular and molecular basis in regulation of both NMDA and AMPA receptors and explored roles of these regulations in stroke damages. He discovered DAPK1 as a crucial molecule that associates with NMDA receptor NR2B subunit and revealed an essential role of this association in stroke damages (Tu et al., Cell, 2010; Wang et al., Nature Neuroscience 2003; Liu et al., Neuron, 2004; Peng et al., 2006; Yang et al., Neuron 2012).
Dr. Xiang Wei, M.D., Ph.D.
Huazhong University of Science and Technology,China
Professor and director of the cardiovascular surgery department in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Dr. Xiang Wei got his M.D. degree in 1997 in Tongji medical university. Then he worked as a cardiothoracic surgeon in Tongji Hospital. In 2001 and 2002~2003, he worked as a visiting scholar in Prince of Wales Hospital in Hong Kong and the University of Chiete in Italy, respectively. In 2008, he received his Ph.D. degree in Tongji Medical College, Huazhong University of Science and Technology. As a cardiovascular surgeon, he is an expert in various kinds of cardiovascular diseases, especially in coronary heart diseases and great vessel diseases. He also performed nearly 50 heart transplantations. His main research interest focused on heart hypertrophy, heart failure and heart and lung transplantation. In 2004, as the principal investigator, “The research about when to choose thymusectomy to treat patients with myasthenia gravis (MG)” won the third prize of Science and technology progress award in Hubei province, second prize of Science and technology progress award in Wuhan city.” He has published about 30 research articles in peer-reviewed journals, including Cardiovascular Research and The Annals of thoracic surgery and so on. He was also in charge of seven grants from the NFSC, Natural science foundation of Hubei province and Wuhan city and Huazhong University of Science and Technology.
Qi Wan , Ph.D.
Wuhan University, China
Dr. Qi Wan is the Professor of Physiology and Vice Dean for Research at Wuhan University School of Medicine. For many years, Dr. Wan has studied the molecular mechanisms mediating the role of glutamate and GABA-A receptors in synaptic plasticity and how dysfunction of these receptors in ischemic neuronal injury and neurodegenerative diseases. His group also investigated the role of migration of neural stem cells in brain repair. His research has led him to publish significant amount of papers in high impact in journals such a Nature, Nature Neuroscience and Nature Medicine. Dr. Wan had his medical training in the Third Military Medical University and obtained his MD degree in 1984. In 1989 he obtained his Master degree in the same university. In 1993, Dr. Wan went to University of Hong Kong to start his PhD training under a collaborated program between University of Hong Kong and University of Toronto. He successfully obtained his PhD degree in 1996. After his medical training, Dr. Wan worked as a Research Scientist in the Research Institute of Surgery at Third Military Medical University for six years. After he completed his postdoctoral training in University of Toronto in 1999, he was appointed as a Scientist at Toronto Western Research Institute and Assistant Professor in the Department of Physiology at University of Toronto. In 2006, he was promoted as Senior Scientist. In 2008 he went to University of Nevada School of Medicine to work as a tenure Associate Professor. He then worked at Wuhan University in January 2013.
Deyin Guo, Ph.D.
Wuhan University, China
Dean of the School of Basic Medical Sciences, Wuhan University, Professor in medical virology and molecular biology. He received his Ph.D in Micro- biology from Brauschweig University of Technology in Germany in 1995. He then worked at Institute of Biotechnolgy and Medical Faculty, University of Helsinki, Finland until 2002 as postdoctoral fellow and docent. Since 2002, he has been a professor at Wuhan University and a princinpal investigator at the National Key Laboratory of Virology. He acted as vice dean of the College of Life Sciences from 2004-2011 and as dean of the School of Basic Medical Sciences, Wuhan University since 2011. He has published over 60 research papers in the peer-reviewed international journals including PNAS, PLoS Pathogens, J. Virol, J. Immunol and JBC. He was an awardee of the Fund for National Execellent Young Researchers, and is a leading scientist of the “973” National Basic Rsearch Program for cellular antiviral innate immunity. His research area covers molecular mechanisms of the replication of viral RNA genome and development of novel strategies for virus control. His work focuses on RNA genome modification, immune escape and drug screening of the newly emerging RNA viruses like SARS coronavirus. He is also interested in gene therapy of HIV/AIDS with exo vivo manipulation and refusion of autologous hematopoietic stem cells
Wuhan University, China
Xiao-Dong Zhang received his Ph.D. in Molecular Biology from School of Basic Medicine of Peking Union Medical College (PUMC) in 2000 for work on cloning and functional study of differentially expressed genes in spermatogenesis of rat and human and continued to work at PUMC. In 2004, he was a postdoctoral fellow in Georgetown University, where he was focus on the functional study of differentially expressed genes in spermatogonia using knockout mice. In 2005, he moved to Case Western Reserve University and involved in the study of dissecting the signaling pathways controlled by phosphatases that are mutated in cancer using somatic cell knockout technique. Dr. Zhang joined College of Life Sciencese in Wuhan University in August, 2008. Currently, Dr. Zhang has set up a laboratory in the Wuhan University and focuses on developing gene targeting technique and dissecting the role of NLK in myocardial angiogenesis and ischemic heart disease using genetic animal models.
Yan Zhou, M.D.,Ph.D.
Wuhan University, China
Yan Zhou, MD/PhD, Professor, College of Life Sciences, Wuhan University. Dr. Zhou obtained Bachelor of Medicine in Tongji Medical College in 1997. He earned MD and PhD degrees in Peking Union Medical College in 2000 and 2002 respectively. Dr. Zhou did his postdoctoral training in Dr. Weimin Zhong’s lab in the Department of Molecular, Cellular and Developmental Biology at Yale University, studying asymmetric cell divisions of neural progenitor cells (NPCs) in cortical development. His studies revealed a novel cellular mechanism that uses Golgi fragmentation and reconstitution, through changes in the subcellular distribution of an essential Numb partner, the Acbd3 protein, to coordinate cell-cycle progression and cell-fate specification during an asymmetric cell division, which is published in Cell and highlighted in Faculty of 1000 and Science Signaling. Dr. Zhou established his own research group in College of Life Sciences, Wuhan University in 2011 and studies molecular and cellular mechanisms underlying cell-fate specification of neural stem/progenitor cells in cortical development and gliomagenesis. His lab recently found long non-coding RNAs are key players in regulating asymmetric cell fates of NPCs. Dr. Zhou is the member of SFN, HUGO and SDB.
Zan Huang, Ph.D.
Wuhan University, China
Dr Huang got his PhD from Loyola University Chicago in 2006. He received his postdoctoral training in the field of hematology and oncology at University of Chicago and Northwestern University. He was appointed as a professor in Wuhan University College of Life Sciences in 2010. Dr. Huang has longstanding research interest in understanding the mechanism and regulation of normal or malignant blood cell differentiation. Particularly, he studied interferon-signaling and transcriptional regulation in megakaryocyte differentiation (J Clin Invest, 2007; Mol Cell Biol, 2009), and TPO/c-MPL signaling in myeloproliferative neoplasms (Lekemia, 2013). Recently, his research extended to unveil the unknown function of novel genes identified in human embryo development (J Biol Chem, 2012; Cell Mol Life Sci, 2013).
Wuhan University, China
Dr. Fan got his PhD from Zhejiang University. Subsequently, he was trained in the field of gene/cell therapy as a postdoc fellow at the Beijing Institute of Radiation Medicine. In 2000, he moved to the University of Cincinnati and involved in the study of cardiovascular disease. Recently，Dr. Fan’s group reported that miR-320 is detrimental, whereas miR-494 is beneficial to the treatment of ischemic heart disease (Circulation, 2009 & 2010). Interestingly, his group discovered that the miR-144/451 cluster is required for the ischemic preconditioning-induced cardioprotection (Cardiovasc. Res. 2012). Dr. Fan serves as an editorial board member for several international journals (i.e. PLoS One; Current Angiogenesis; Am. J. Cardiovas. Dis.), reviews manuscripts for more than 20 journals (Circulation; Circ. Res.; JCI; PNAS; JBC; MCB; etc) and grant proposals for AHA and NIH. Currently, Dr. Fan has set up a laboratory in the Wuhan University and focuses on dissecting the role of exosomal signaling pathway in myocardial angiogenesis and ischemic heart disease using genetic animal models.
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