Basic Sciences Investigators
Kenneth Walsh, Ph.D.
The Director of the Whitaker Cardiovascular Institute, he is the Aram V. Chobanian Distinguished Professor of Medicine. He received a PhD in Biochemistry from the University of California, Berkeley. He has published more than 300 scientific articles and is the recipient of multiple research grants from the National Institutes of Health, including a MERIT Award. He is the past recipient of an Established Investigator Award of the American Heart Association and has received the Irwin F. Page Investigator Award from the Council on Arteriosclerosis. Dr. Walsh is a fellow of the Council on Basic Cardiovascular Research and he was recently designated Distinguished Investigator of the American Heart Association. He is a member of the CCHF study section for the National Institutes of Health. Dr. Walsh is an Associate Editor for the journal Circulation and a member of numerous editorial boards including Circulation Research, Arteriosclerosis, Thrombosis and Vascular Biology, Journal of Molecular and Cellular Cardiology, Hypertension Research, Skeletal Muscle and Science Signaling.
The Walsh laboratory investigates the signaling- and transcriptional-regulatory mechanisms that control both normal and pathological tissue growth in the cardiovascular system. Many of these studies involve analyses of the PI3-kinase/Akt/GSK/Forkhead signaling axis. This pathway is of critical importance in the regulation of organ growth and body size. Signaling through this pathway controls cellular enlargement (hypertrophy), cell death (apoptosis), and blood vessel recruitment and growth (angiogenesis). Related studies examine how alterations in the expression of adipocyte-derived cytokines, referred to as adipokines, interfere with normal signaling within the cardiovascular system and thereby contribute to cardiovascular disease. Finally, they examine how age-associated loss of skeletal muscle mass affects metabolic and cardiovascular function, and are exploring the possibility that muscle-secreted factors (myokines) confer some of the benefits of exercise training on cardiovascular and metabolic diseases.
- K.N. Papanicolaou, R.J. Khairallah, G. Ngoh, A. Chikando, I. Luptak, K. O’Shea, D.D. Riley, J.J. Lugus, W.S. Colucci, W.J. Lederer, W.C. Stanley, K. Walsh (2011). Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol Cell Biol. 31:1309-1328
- N. Ouchi, A. Higuchi, K. Ohashi, Y. Oshima, N. Gokce, R. Shibata, Y. Akasaki, A. Shimono, K. Walsh (2010). Sfrp5 Is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 329:454-457. Accompanied by editorial.
- Y. Izumiya, T. Hopkins, C. Morris, K. Sato, L. Zeng, J. Viereck, J.A. Hamilton, N. Ouchi, N.K. LeBrasseur, K. Walsh (2008). Fast/glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metabolism 7:159-172. Accompanied by editorial.
- R. Shibata, K. Sato, D.R. Pimentel, Y. Takemura, S. Kihara, K. Ohashi, T. Funahashi, N. Ouchi, K. Walsh (2005). Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2- dependent mechanisms. Nature Med. 10: 1096-1103. Accompanied by editorial.
- Shiojima, K. Sato, Y. Izumiya, S. Schiekofer, M. Ito, R. Liao, W.S. Colucci, K. Walsh (2005). Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J. Clin. Invest. 115:2108-2118. Accompanied by editorial.
- R. Shibata, N. Ouchi, M. Ito, S. Kihara, I. Shiojima, D.R. Pimentel, M. Kumada, K. Sato, S. Schiekofer, K. Ohashi, T. Funahashi, W.S. Colucci, K. Walsh (2004). Adiponectin-mediated modulation of hypertrophic signals in the heart. Nature Med. 10:1384-1389.
Dr. Akey is a Professor in the Department of Physiology and Biophysics. His research focuses on the structure and function of large macromolecular machines and protein complexes. Dr. Akey was trained in structural electron microscopy by Drs. Stuart Edelstein (Ph.D. adviser at Cornell University) and Nigel Unwin (post-doctoral mentor at Stanford) and was also a visiting scientist at the Laboratory of Molecular Biology in Cambridge, England. Dr. Akey has lectured in Cell Biology and mentors Discussion sessions in Endocrinology. He also teaches a module on structural electron microscopy in “Foundations of Biophysics and Structural Biology”, which is taught each year. His research is supported by two NIH grants and he currently sits on the Molecular Structure and he recently served on the Molecular Structure and Function C study section for the National Institutes of Health.
- Yuan, S., Yu, X., Topf, M., Dorstyn, L., Kumar, S., Ludtke, S.J., and Akey, C.W. (2011). Structure of the Drosophila apoptosome at 6.9Å resolution. Structure 19, 128-140.
- Yuan, S., Yu, X., Topf, M., Ludtke, S.J., Wang, X. and Akey, C.W. (2010). Structure of an apoptosome procaspase-9 CARD complex. Structure 18, 571-583.
- Raychaudhury, S., Farelli, J., Montminy T.P., Ménétret, J.F., Matthews, M., Roy, C.R., Head, J.F., Isberg, R.R. and Akey, C.W. (2009). The structure and function of interacting domains of IcmR-IcmQ from the Type IVb secretion system of Legionella pneumophila. Structure 17, 590-601.
- Ménétret, J. F., Hegde, R.S., Woong, K., Gygi, S.P., Rapoport, T. A., and Akey, C. W. (2008). Single copies of Sec61 and TRAP associate with a nontranslating mammalian ribosome. Structure 16, 1126-1137.
- Chandramouli, P., Topf, M., Ménétret, J.F., Eswar, N., Gutell, R.R., Sali, A., and Akey, C.W. (2008). Structure of the mammalian 80S ribosome at 8.7Å resolution. Structure 16, 535-548.
- Ménétret, J.F., Schaletsky, J., Clemons, W.M. Jr., Osborne, A.R., Skanland, S., Denison, C., Gygi, S.P., Kirkpatrick, D.S., Park, E., Ludtke, S.J., Rapoport, T.A. and Akey, C.W. (2007). Ribosome binding of a single copy of the SecY complex: implications for protein translocation. Molecular Cell 28, 1083-1092.
Tamar Aprahamian, Ph.D, Assistant Professor
An Assistant Professor of Medicine, Dr. Aprahamian obtained a B.S. in Biology at Boston College, and a Ph.D. from the program of Cell, Molecular and Developmental Biology at Tufts University Sackler School of Biomedical Sciences. Her research studies have included developing a novel mouse model to study the interactions between atherosclerosis and autoimmunity.This revealed a synergy between the two disease processes promoted by impaired apoptotic clearance. Continued studies demonstrated beneficial effects of simvastatin on a mouse model of accelerated atherosclerosis and lupus. Dr. Aprahamian received a K-01 to study the role of PPARgamma agonists and adiponectin in systemic lupus erythematosus. She was the first to show that the immunomodulatory effects of PPARgamma agonists can ameliorate lupus-like disease, and lupus-associated atherosclerosis in several mouse models and this effect is mediated by adiponectin. Recently, she has started exploring the role of adiponectin in the adipose tissue microenvironment, and its effects on systemic metabolism and obesity-related inflammation.
- Aprahamian T, Rifkin I, Bonegio R, Hugel B, Freyssinet JM, Sato K, Castellot JJ Jr, Walsh K. (2004) Impaired clearance of apoptotic cells promotes synergy between atherogenesis and autoimmune disease. J Exp Med 199:1121-1131.
- Aprahamian T, Bonegio R, Rizzo J, Perlman H, Lefer DJ, Rifkin I, Walsh K (2006). Simvastatin treatment ameliorates autoimmune disease associated with accelerated atherosclerosis in a murine lupus model. J Immunol (Sep 1;177(5):3028-34).
- Aprahamian, T., Bonegio, RG., Richez, C., Yasuda, K., Chiang, L-K, Sato, K., Walsh, K., Rifkin, I. (2009) The Peroxisome Proliferator-Activated Receptor Gamma Agonist Rosiglitazone Ameliorates Murine Lupus By Induction Of Adiponectin. Journal of Immunology. Jan 1; 182(1):340-6
- Parker J, Menn-Josephy H, Laskow B, Takemura Y,Aprahamian T. (2011) Modulation of Lupus Phenotype by Adiponectin Deficiency in Autoimmune Mouse Models. Journal of Clinical Immunology. Apr;31(2):167-73.
Aprahamian TR, Sam F.Int J Inflam. 2011;2011:376909.
Elevated adiponectin expression promotes adipose tissue vascularity under conditions of diet-induced obesity.Aprahamian TR.Metabolism. 2013 Dec;62(12):1730-8.
A Professor of Physiology and Biophysics, Research Professor of Biochemistry and Chair of the Department of Physiology and Biophysics, is the past recipient of an Established Investigator of the American Heart Association. Dr. Atkinson is a member of the National Institutes of Health, Heart Lung and Blood Program Project Review Committee. Dr. Atkinson directs a Program Project “Structural and Cell Biology in Cardiovascular Disease” and is the leader of a component project on “Lipoprotein Structure and Apolipoprotein Conformation”. His research focuses on the molecular details of the structure, stability and dynamic properties of the plasma lipoproteins and their constituent apolipoproteins, particularly high density (HDL, “Good Cholesterol”) and low density (LDL, “Bad Cholesterol”).
- Hongli L. Zhu and David Atkinson. Conformation and Lipid Binding of the N-Terminal (1-44) Domain of Human Apolipoprotein A-I Biochemistry; 2004; 43(41) pp 13156 – 13164. PubMed PMID: 15476409; PubMed Central PMCID: PMC2518689.
- Gorshkova IN, Liu T, Kan HY, Chroni A, Zannis VI, Atkinson D. Structure and stability of apolipoprotein A-I in solution and in discoidal high-density lipoprotein probed by double charge ablation and deletion mutation. Biochemistry. 2006 Jan 31;45(4):1242-54. PubMed PMID: 16430220; PubMed Central PMCID: PMC2532493.
- Zhu H.L., Atkinson D. Conformation and lipid binding of a C-terminal (198-243) peptide of human apolipoprotein A-I. Biochemistry. 2007 Feb 13;46(6):1624-34. PubMed PMID: 17279626; PubMed Central PMCID: PMC2518689.
- Gorshkova I. N, Kypreos KE, Gantz DL, Zannis VI, Atkinson D. Biophysical properties of apolipoprotein E4 variants: implications in molecular mechanisms of correction of hypertriglyceridemia. Biochemistry. 2008 Nov 25;47(47):12644-54. PubMed PMID: 18959431; PubMed Central PMCID: PMC2748909.
- Yuhang Liu and David Atkinson. Enhancing the Contrast of ApoB to Locate the Surface Components in the 3D Density Map of Human LDL. J. Mol. Biol. (2011) 405, 274–283. PubMed PMID: 21029740.
- Yuhang Liu, Dong Luo, and David Atkinson. Human LDL core cholesterol ester packing: 3D image reconstruction and SAXS simulation studies J. Lipid Res. jlr.M011569. First Published on November 3, 2010, doi:10.1194/jlr.M011569. PubMed: PMID: 21047995.
Victoria M. Bolotina, Ph.D.
An associate professor of medicine and physiology, she is a recipient of multiple awards from the NIH and American Heart Association. She serves on the NIH and American Heart Association peer review committees. Her research focus is on ion channels and mechanisms of calcium signaling in the cardiovascular system. An integrative approach is used to unveil new mechanisms of vascular contraction and relaxation: patch clamp, high resolution confocal and deconvolution imaging, and molecular and biochemical techniques (including knock-out mice models) are used in her laboratory to study single channels and whole-cell currents, regulation of membrane potential, intracellular calcium and vascular tone, as well as expression, activity, and localization of several major determinants in calcium signaling cascades. The large part of her recent research is devoted to studying the mysterious store-operated channels and capacitative calcium influx pathway in variety of cell types, including (but not limited to) smooth muscle cells, cardiomyocytes, platelets, and T-lymphocytes.
A professor of medicine and pharmacology, he is the John I. Sandson Distinguished Professor of Health Sciences. He has previously served as President of Boston University, Medical Campus Provost, and Dean of Boston University School of Medicine. He has had a long-standing interest in hypertension and vascular biology. He has been honored as the recipient of the first Bristol-Meyers Squibb Lifetime Achievement Award in Hypertension, the Modern Medicine Award for Distinguished Achievement, the Award of Merit of the American Heart Association (AHA), the Freis Award of the National High Blood Pressure Program, and the Lifetime Achievement Award of the Massachusetts Medical Society. He has chaired several scientific committees including the National Heart, Lung and Blood Institute (NHLBI) Task Force on Research in Hypertension; the Fourth and Seventh Joint National Committees on Detection, Evaluation and Treatment of High Blood Pressure; the Food and Drug Administrations’s Cardiorenal Advisory Committee; the NHLBI’s Advisory Committee on Hypertension and Arteriosclerosis; and the Council for High Blood Pressure Research of the AHA. He has been a member of the Advisory Council of the NHLBI. Dr. Chobanian has been on the editorial boards of the New England Journal of Medicine, Hypertension, the Journal of Hypertension, Blood Pressure, Hypertension Research, the Journal of Vascular Biology, and Heart Disease. He was elected to the Association of American Physicians and the American Society for Clinical Investigation and is a Fellow of the American Academy of Arts and Sciences.
- Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT,
- Roccella EJ and the National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 Report. JAMA 289: 2560-2572, 2003.
- Chobanian AV. Isolated systolic hypertension in the elderly. N Engl J Med 2007; 357:789-96.
- Chobanian AV. Does it matter how hypertension is controlled? N Engl J Med 2008;359:2485-2488.
- Chobanian AV. Shattuck Lecture. The hypertension paradox–more uncontrolled disease despite improved therapy. N Engl J Med 2009;361:878-87. (editorial)
- Chobanian AV. The impact of nonadherence to antihypertensive therapy. Circulation 2009;120:1558-60. (editorial)
- Chobanian AV. Improved hypertension control. Cause for some celebration. JAMA 2010;303:2082-3. (editorial)
A professor of Medicine, Physiology, and Pharmacology and Experimental Therapeutics, Dr. Cohen is the Jay and Louise Coffman Professor of Medicine and Director of the Vascular Biology Unit. Dr. Cohen is also the Co-principal Investigator of the Boston University Cardiovascular Proteomics Center. Dr. Cohen is also a recipient of a MERIT award from the NHLBI. He is a former recipient of the American Heart Association Clinician Investigator and the Established Investigator awards. He is past president of the American Federation for Medical Research and founding president of the American Federation for Medical Research Foundation. Dr. Cohen is distinguished by his elections to the American Society for Clinical Investigation and the Association of American Physicians. He is an elected Fellow of the Cardiovascular Section of the American Physiological Society. He is a member of the editorial boards of the American Journal of Physiology: Heart and Circulatory Physiology and Arteriosclerosis, Thrombosis, and Vascular Biology, and Free Radical Biology and Medicine. Dr. Cohen is a past member of the NIH Experimental Cardiovascular Study Section and currently serves as an ad hoc reviewer for several NIH review groups. The research in the Vascular Biology Unit which Dr. Cohen directs focuses on the effect of vascular and metabolic disease on the function of blood vessels with special emphasis on the role of endothelium-derived nitric oxide and reactive oxygen species. The roles of redox mediated post-translational protein modifications of cardiovascular proteins including the sarcoplasmic reticulum calcium ATPase, sirtuin-1, and p21ras in cell signaling and disease are a current focus.
- Evangelista AM, Thompson MD, Weisbrod RM, Pimental DR, Tong X, Bolotina VM, Cohen RA. Redox regulation of SERCA2 is required for vascular endothelial growth factor-induced signaling and endothelial cell migration. Antioxid Redox Signal. 2012; 17(8):1099-108. PMID: 22472004; PMC3423867.
- Evangelista AM, Thompson MD, Bolotina VM, Tong X, Cohen RA. Nox4- and Nox2-dependent oxidant production is required for VEGF-induced SERCA cysteine-674 S-glutathiolation and endothelial cell migration. Free Radic Biol Med. 2012: S0891-5849(12)01777-7. 10.1016/j.freeradbiomed.2012.
10.546. [Epub ahead of print] PubMed PMID: 23089226.
- Weisbrod RM, Shiang T, Al Sayah L, Fry JL, Bajpai S, Reinhart-King CA, Lob HE, Santhanam L, Mitchell G, Cohen RA, Seta F. Arterial stiffening precedes systolic hypertension in diet-induced obesity. Hypertension. 2013 Dec;62(6):1105-10. PubMed PMID: 24060894.
- Shao D, Fry JL, Han J, Hou X, Pimentel DR, Matsui R, Cohen RA, Bachschmid MM. A redox-resistant sirtuin-1 mutant protects against hepatic metabolic and oxidant stress. J Biol Chem. 2014 Jan 22. [Epub ahead of print] PubMed PMID: 24451382
- Murdoch CE, Shuler M, Haeussler DJ, Kikuchi R, Bearelly P, Han J, Watanabe Y, Fuster JJ, Walsh K, Ho YS, Bachschmid MM, Cohen RA, Matsui R. Glutaredoxin-1 up-regulation induces soluble vascular endothelial growth factor receptor 1, attenuating post-ischemia limb revascularization. J Biol Chem. 2014 Jan 30. E-Pub ahead of print. PMID: 24482236.
The Thomas J. Ryan Professor of Medicine and Professor of Physiology, he is Chief of Cardiovascular Medicine at Boston Medical Center and Boston University School of Medicine, Co-Director of the Cardiovascular Center at Boston Medical Center, and Head of the Myocardial Biology Unit at Boston University School of Medicine. He is the author of over 160 peer-review publications, as well as numerous reviews, chapters and books dealing with the pathophysiology of myocardial failure. He has received the Clinician-Scientist and Established Investigator Awards of the American Heart Association, the Medal of Merit from the International Society of Heart Research, and was elected to the American Society of Clinical Investigation. He is a member of several American Heart Association Councils, including Basic Science, High Blood Pressure, and Circulation, and is a Fellow of the American College of Cardiology and a member of the Association of University Cardiologists. He is a member of the Executive Council of the Heart Failure Society of America, an organization of which he is a founding member. He has been a member of numerous peer-review groups and currently is the Co-chairman of the American Heart Association, Northeast Affiliate, Scientific Peer Review Committee, and a member of the National Institutes of Health Cardiovascular and Renal Study Section.
A professor of medicine, he is Chief of the Hypertension Section at Boston University School of Medicine. He was the first investigator to introduce the use of angiotensin converting enzyme inhibitors for the treatment of hypertension and heart failure. Dr. Gavras is a former AHA Established investigator. He was elected to the American Society of Clinical Investigation and has served on the NIH’s Cardiovascular and Renal Study Section and on many scientific advisory committees. He is a past Chairman of the American Heart Association’s Hypertension Council, a past president of the Inter-American Society of Hypertension and the American Society of Hypertension. Dr. Gavras has received numerous honors and awards from national and international societies for his research on the role of the renin-angiotensin system and its inhibition in the treatment of hypertension and heart failure. He is also on the editorial boards of several medical journals, including Hypertension, the Journal of Hypertension and the American Journal of Hypertension.
- Sun B, Kintsurashvili E, Ona D, Ignjacev-Lazich I, Gavras I, Gavras H: Inhibition of the alpha(1D)-adrenergic receptor gene by RNA interference (RNAi) in rat vascular smooth muscle cells and its effects on other adrenergic receptors. Vascul Pharmacol 46:367-372, 2007.
- Duka A, Kintsurashvili E, Duka I, Ona D, Hopkins TA, Bader M, Gavras I, Gavras H: Angiotensin-converting enzyme inhibition after experimental myocardial infarct: role of the kinin B1 and B2 receptors. Hypertension 51:1352-1357, 2008.
- Kintsurashvili E, Shenouda S, Ona D, Ona L, Ahmad S, Ravid K, Gavras I, Gavras H: Hypertension in transgenic mice with brain-selective overexpression of the alpha2B-adrenoceptor. Am J Hypertens 22:41-45, 2009.
- McCalmon SA, Desjardins DM, Ahmad S, Davidoff KS, Snyder CM, Sato K, Ohashi K, Kielbasa OM, Mathew M, Ewen EP, Walsh K, Gavras H, Naya FJ: Modulation of Angiotensin II-Mediated Cardiac Remodeling by the MEF2A Target Gene Xirp2. Circ Res 106: 952-960, 2010.
- Lucero HA, Kintsurashvili E, Marketou ME, Gavras H: Cell signaling, internalization and nuclear localization of the angiotensin converting enzyme in smooth muscle cells and endothelial cells. J Biol Chem 285:5555-5568, 2010.
- Marketou M, Kintsurashvili E, Papanicolaou KN, Lucero HA, Gavras I, Gavras H. Cardioprotective effects of a selective B2 receptor agonist of bradykinin post acute myocardial infarct. Am J Hypertens 23:562-568, 2010.
- Manolis AJ, Marketou ME, Gavras I, Gavras H: Cardioprotective properties of bradykinin: role of the B2 receptor. Hypertens Res 33:772-777, 2010.
A professor of medicine and member of the Hypertension Section, she has been responsible for the clinical aspects of the Section’s research activities, such as evaluation of the hemodynamic, metabolic, and humoral results of administration of angiotensin antagonists, vasopressin antagonists, etc. in patients with hypertension and/or heart failure. She has served on the NIH’s Cardiovascular Study Section B, on the Program Committee, the Publication Committee and Chairman of the Professional Education Committee of the American Heart Association’s Hypertension Council, as well as the Program Committee and Specialists Examination Committee of the American Society of Hypertension, and is on the editorial board of Hypertension and the American Journal of Hypertension.
The representative publications of Dr. Irene Gavras may be found above, with those of Dr. Haralambos Gavras.
David A. Goukassian, MD, PhD
NASA Human Research Program (IRP) identified space irradiation (IR) as one of the space flight risk factors to the cardiovascular (CV) system. In addition, long-duration space missions such as work on ISS, future lunar, near Earth asteroid, and Mars missions, as well as emerging civilian space travel activities, necessitate ground-based studies on degenerative CV risk assessment of space IR. Our laboratory has been funded by NASA to examine the effects of a single low dose space IR (specifically, 50 cGy, 1 GeV of ionized proton and 15 cGy, 1 GeV/n of ionized iron, days and up to 10 months after initial IR exposure) on the function of the heart during normal aging as well as on ability of the heart to recovery after an ischemic CV event, i.e., acute myocardial infarct -AMI. Further, our research is aimed at understanding the harmful effects of terrestrial ionizing radiation, specifically, cancer radiotherapy of the organs in the close proximity of the heart. Why do we want to study this? There is a large number of published epidemiological reports on evidence of increased incidence of CV diseases in cancer patients treated with radiotherapy emitters, this would be high dose radiation in multiple fraction, non-occupational (nuclear accidents such as Chernobyl and Fukushima) and occupational exposure (nuclear plant workers, radon miners, nuclear submarine crew). Moreover, a very recent report revealed 2.5-fold elevated mortality risk after cardiac surgery in cancer survivor patients 5-18 years after radiotherapy. Our goals are: (1) to understand and determine the early signs of increased cardiovascular risks due to cancer radiotherapy; (2) discover and eventually development prognostic factors/bio-markers for predicting ionizing radiation(IR)-mediated CV decease risks; (3) determine molecular mechanisms underlying the harmful effects of IR on CV health.
- Shtifman A, Pezone MJ, Sasi SP, Agarwal A, Gee H, Song J, Perepletchikov A, Yan X, Kishore R, Goukassian DA. Divergent modification of low-dose (56)Fe-particle and proton radiation on skeletal muscle. Radiat Res. 2013 Nov;180(5):455-64.
- Zhou J, Cheng M, Liao YH, Hu Y, Wu M, Wang Q, Qin B, Wang H, Zhu Y, Gao XM, Goukassian D, Zhao TC, Tang YL, Kishore R, Qin G. Rosuvastatin enhances angiogenesis via eNOS-dependent mobilization of endothelial progenitor cells. PLoS One. 2013 May 21;8(5):e63126.
- Goukassian D.A. Morgan J, Yan X. Neuregulin1-ErbB Signaling in Doxorubicin-Induced Cardiotoxicity. Publisher Intech, Ed.: Manuela Fiuza, Book Chapter in: Cardiotoxicity of Oncologic Treatments. pp. 65-88, 2012. (6 months after publication there were more than 1,000 full downloads worldwide).
- Klement G.L., Goukassian D.A., Hlatky L., Carrozza J., Morgan J.P., Yan X. Cancer Therapy Targeting the HER2-PI3K Pathway: Potential Impact on the Heart. Frontiers in Pharmacology, 3:113, 2012.
- Sasi SP, Yan X, Enderling H, Park D, Gilbert HY, Curry C, Coleman C, Hlatky L, Qin G, Kishore R, Goukassian D.A. Breaking the ‘Harmony’ of TNF-α Signaling for Cancer Treatment. Oncogene, 567, pp 1-11, 2011.
- Kishore R,Tkebuchava T, Sasi SP, Silver M, Gilbert H-Y, Yoon Y-S, Park H-Y, Thorne, T, Losordo W, Goukassian D.A. Tumor Necrosis Factor-α Signaling Via TNFR1/p55 is Deleterious whereas TNFR2/p75 Signaling is Protective in Adult Infarct Myocardium. Adv Exp Med Biol 691: pp. 433-48, 2011.
- Goukassian D.A., Qin G., Dolan C., Murayama T., Silver M., Curry C., Eaton E., Luedemann C., Ma H., Asahara T., Zak V., Mehta S., Burg A., Thorne T., Kishore R., Losordo D.W. Tumor Necrosis Factor-alpha Receptor p75 is Required in Ischemia-induced Neovascularization. Circulation 115(6): pp. 752-62, 2007.
A professor of biophysics and physiology, research professor of medicine, and Director of the NMR Facility, is the Director of the Cardiovascular Magnetic Resonance Spectroscopy and Imaging Center. Dr. Hamilton pioneered applications of NMR spectroscopy for the noninvasive analysis of lipid structures and compositions in atherosclerotic plaques (ex vivo). Current research integrates the NMR analysis with images of plaques, both in vivo and ex vivo. The long-term goals of projects on atherosclerosis are to provide robust interpretations of MR images of plaques, and to distinguish in human arteries vulnerable plaques from stable plaques in vivo before plaque rupture occurs. A second major area of research is the transport of fatty acids in plasma, in membranes, and inside cells. His group has studied the binding of fatty acids to albumin and to intracellular fatty acid binding proteins (FABP) and determined high-resolution tertiary structures of FABP by NMR spectroscopic methods. New fluorescence approaches were developed in his research program to determine how fast fatty acids move across membranes and how fast they enter cells. Dr. Hamilton is a founding organizer of the international workshop, Fatty Acid Uptake Into the Brain. Currently Dr. Hamilton is Associate Editor for Lipids and Obesity Research and a member of the Editorial Board of Journal of Lipid Research.
Victoria L. M. Herrera, M.D.
A pediatric cardiologist trained at Children’s Hospital Boston, Harvard Medical School, is Professor of Medicine, and Director for the Ultrasound Micro-Imaging Core. She was a former NIH Physician Scientist Awardee and received the Syntex Scholar’s Award for excellence in Cardiovascular Research for work done at the Whitaker Cardiovascular Institute. She was a member of the NIH Task Force for Hypertension, AHA Massachusetts Affiliate study section, NIH Cardiovascular-A Study Section, AHA North American Consortium Study Section, and Hypertension editorial board. Currently, she is on the editorial board for Physiological Genomics, and reviewer for NIH program project grants. Her research program focuses on an integrative molecular-genetic analysis of mechanisms underlying the acceleration of coronary artery disease and strokes by hypertension-hyperlipidemia interactions, fetal programming of adult-onset vascular diseases, endothelial injury/repair balance in aging and vascular diseases. More recently, in collaboration with Dr. Nelson Ruiz-Opazo, new research studies focus on the investigation of the dual endothelin-1/VEGFsp receptor as an angiogenesis player relevant to cancer, aging and regenerative medicine.
Dr. Jiang, an Associate Professor of Pharmacology and Medicine, is a member of The Whitaker Cardiovascular Institute and Department of Pharmacology & Experimental Therapeutics. He received Ph.D. in Biochemistry at University College, University of London in England and then postdoctoral training at Joslin Diabetes Center, Harvard Medical School and University of Massachusetts School of Medicine.
Research Interests: Metabolic Syndrome, Obesity, Diabetes and Innate Immunity. Currently, Jiang lab mainly focuses on understanding how insulin signaling networks and innate immunity regulate metabolic functions.
1. Exploring the role of neutrophils and neutrophil elastase (NE) in the development of obesity-related adipose inflammation, insulin resistance and cardiovascular dysfunction. Using quantitative serum proteomic approach, The Jiang lab identified that there is an imbalance between NE and its inhibitor alpha-1-antitrypsin in both obese human subjects and mouse models. Interestingly, both NE knockout mice and human A1AT transgenic mice are resistant to high-fat diet-induced body weight gain, adipose inflammation, fatty liver and insulin resistance. NE knockout mice have higher AMP kinase activity and fatty acid oxidation rate. Currently, Jiang lab is exploring molecular and cellular mechanisms whereby obesity regulates neutrophils activity and subsequent adipose inflammation, fatty liver, insulin resistance and cardiovascular dysfunctions with mouse models.
2. CDP138 and its signal networks related to glucose and lipid metabolisms. Using a SILAC-based quantitative proteomics approach, we identified multiple phosphoproteins from insulin-stimulated adipocytes. As a result, Jiang lab found that CDP138, a novel phosphoprotein containing C2 domain, is involved in the regulation of GLUT4 translocation. With CDP138 knockout mouse model, Jiang lab is using TIRF microscopy-based live cell imaging, protein-protein interactions, gene expression profiling to study the signal network of CDP138 and its role in the regulation of glucose and lipid metabolisms and neuronal functions.
- Mansuy-Aubert V, Zhou QL, Xie X, Gong Z, Huang JY, Khan AR, Aubert G, Candelaria K, Thomas S, Shin DJ, Booth S, Baig SM, Bilal A, Hwang D, Zhang K, Lovell-Badge R, Smith SR, Awan FR, Jiang ZY. Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metab. 2013 Apr 2; 17(4):534-48. PMID:23562077. Full article.
- Xie X, Gong Z, Mansuy-Aubert V, Zhou QL, Tatulian SA, Sehrt D, Gnad F, Brill LM, Motamedchaboki K, Chen Y, Czech MP, Mann M, Krüger M, Jiang ZY. C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane. Cell Metab. 2011 Sep 7;14(3):378-89. PMID:21907143.
- Zhou QL, Jiang ZY, Mabardy AS, Del Campo CM, Lambright DG, Holik J, Fogarty KE, Straubhaar J, Nicoloro S, Chawla A, Czech MP. A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes. J Biol Chem. 2010 Sep 3;285(36):27581-9. PMID: 20587420..
- Zhou QL, Jiang ZY, Holik J, Chawla A, Hagan GN, Leszyk J, Czech MP. Akt substrate TBC1D1 regulates GLUT1 expression through the mTOR pathway in 3T3-L1 adipocytes. Biochem J. 2008 May 1;411(3):647-55. PMID: 18215134.
- Jiang ZY, Zhou QL, Holik J, Patel S, Leszyk J, Coleman K, Chouinard M, Czech MP. Identification of WNK1 as a substrate of Akt/protein kinase B and a negative regulator of insulin-stimulated mitogenesis in 3T3-L1 cells. J Biol Chem. 2005 Jun 3;280(22):21622-8. PMID: 15799971.
- Jiang ZY, Zhou QL, Coleman KA, Chouinard M, Boese Q, Czech MP. Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7569-74. PMID: 12808134.
- Jiang ZY, Chawla A, Bose A, Way M, Czech MP. A phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose transporter recycling. J Biol Chem. 2002 Jan 4;277(1):509-15. PMID: 11694514.
- Jiang ZY, Lin YW, Clemont A, Feener EP, Hein KD, Igarashi M, Yamauchi T, White MF, King GL. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats.J Clin Invest. 1999 Aug;104(4):447-57. PMID: 10449437.
Michael T. Kirber, Ph.D., Associate Professor
Is an Associate Professor of Medicine and Technical Director of the Cellular Imaging Core. His research involves the development and application of advanced imaging systems for use in fluorescence microscopy. Biological interests focused on the study of the relationships existing between ion channel activity, intracellular calcium, and the contractile state of smooth muscle. He has studied mechanisms linking the activity of cation-selective mechanically gated ion channels to voltage gated calcium-selective channels and the release of calcium from intracellular storage sites in smooth muscle, processes which may be essential to certain myogenic responses. His research also involves spontaneous local release of intracellular calcium, known as calcium sparks. He performed the first three dimensional imaging of calcium sparks, which suggested the existence of microdomains within the cell which are important in determining the relationship between calcium sparks and spontaneous outward currents which they can generate. Other recent efforts involved the relationship between protein kinase C activity and the release of calcium from intracellular stores, which may be a novel physiologically important negative feedback regulatory mechanism.
Dr. Kirber’s education is in electrical and biomedical engineering. He did his post-doctoral training in the Physiology Department at University of Massachusetts Medical School where he studied smooth muscle cells using patch clamp techniques.
- Kirber, M.T., Guerrero, A., Tuft, R.A., Bowman, D.S., Singer, J.J. and Fay, F.S. Multiple pathways responsible for stretch-induced elevation of calcium concentration in smooth muscle cells. J. Physiol. 524:1 3-17, 2000
- Kirber, MT; Etter, EF; Bellve, KA; Lifshitz, LM; Tuft, RA; Fay, FS; Walsh, JV.. Relationship of Ca2+ sparks to STOCs studied with 2D and 3D imaging in feline oesophageal smooth muscle cells. Journal of Physiology. 531(Pt 2):(Mar 1): 315-327, 2001.
- Karsten Bahlmann, Peter T. So, Michael Kirber, Robert Reich, Bernard Kosicki, William McGonagle, Karl Bellve. Multifocal multiphoton microscopy (MMM) at a frame rate beyond 600 Hz. Optics Express, Vol. 15, Issue 17, pp. 10991-10998 (August 2007).
- Kirber MT, Chen K, Keaney JF Jr. YFP photoconversion revisited: confirmation of the CFP-like species. Nat Methods. 2007 Oct;4(10):767-8.
- Peng H, Yaney GC, Kirber MT. Modulation of Ca(2+) release through ryanodine receptors in vascular smooth muscle by protein kinase C alpha. Pflugers Arch. 2010 Sep;460(4):791-802. Epub 2010 Jun 23.
Edward J. Miller, MD Ph.D., Assistant Professor of Medicine and Radiology
Dr. Miller is an Assistant Professor of Medicine and Radiology and is an active investigator in areas of cardiomyocyte metabolism, mitochondrial function, infiltrative cardiomyopathy (sarcoidosis and amyloidosis), and cardiac nuclear imaging. Dr. Miller received his B.S degree cum laude from the University of Notre Dame, MD degree from Loyola University Stritch School of Medicine, and his PhD with distinction from Yale University. Dr. Miller is currently the recipient of a K08 award focused the role and regulation of the LKB1-AMPK axis in metabolic heart disease, as well as a BU Department of Medicine award investigating non-invasive imaging of cardiac mitochondrial function in vivo.
- Baron S, Li J, Russell RR, Neumann D, Miller EJ, Tuerk R, Walliman T, Hurley R, Witters LA, Young LH. Dual mechanisms regulating AMPK kinase action in the ischemic heart. Circulation Research, 2005. 96(3): p. 337-45.
- Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR, Young LH. AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circulation Research. 2005. 97(9):872-9. Epub 2005 Sep 22.
- Li J, Coven DL, Miller EJ, Hu X, Young ME, Carling D, Sinusas AJ, Young LH. Activation of AMPK α- and γ- Isoform Complexes in the Intact Ischemic Rat Heart. Am J Physiol Heart Circ Physiol. Oct;291(4):H1927-34. Epub April 28, 2006
- Miller EJ, Li J, Sinusas K, Holman GD, Young LH. Infusion of a biotinylated bis-glucose photolabel: A new method to quantify cell-surface GLUT4 in the intact mouse heart. Am J Physiol Endo. 2007. June;292(6):E1922-8. Epub 2007 Mar 6.
- Miller EJ, Li J, Leng L, McDonald C, Atsumi, T, Bucala R, Young LH. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischemic heart. Nature. 2008. Jan 31;451(7178): 578-82.
- Amundson D, Dadekian G, Etienne M, Gleeson T, Hicks T, Killian D, Kratovil K, Lewis C, Monsour M, Pasiuk B, Rhodes D, Miller EJ. Practicing Internal Medicine Onboard the USNS COMFORT in the Aftermath of the Haitian Earthquake. Ann Intern Med. 2010 Jun 1;152(11):733-7. Epub 2010 Mar 2
- Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K, Young LH. A small molecule AMPK activator protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol. 2011 Jul;51(1):24-32
- Qin F, Siwik DA, Luptak I, Hou X, Wang L, Higuchi A, Weisbrod RM, Ouchi N, Tu VH, Calamaras TD, Miller EJ, Verbeuren TJ, Walsh K, Cohen RA, Colucci WS. The Polyphenols Resveratrol and S17834 prevent the Structural and Functional Sequelae of Diet-Induced Metabolic Heart Disease in Mice. Circulation. 2012 Apr 10; 125(14):1757-64
- Li J, Miller EJ, Young LH. Urocortin 2 Autocrine/aracrine and Pharmacologic Effects to Activate AMP-Activated Protein Kinase in the Heart. PNAS. 2013 Oct 1;110(40):16133-8.
- Berman JS, Govender P, Ruberb FL, Mazzini M, Miller EJ. Scadding Revisited: A Proposed Staging System for Sarcoidosis Based on Advanced Imaging. Sarcoidosis Vasc Diffuse Lung Dis. 2014. In Press.
- Ahmadian A, Brogan A, Berman JS, Sverdlov AL, Mercier G, Mazzini M, Govender P, Ruberg RL, Miller EJ. Quantitative Interpretation of FDG PET/CT with Myocardial Perfusion Imaging Increases the Diagnostic Information in the Evaluation of Cardiac Sarcoidosis. J Nuc Card. 2014. In Press.
A Professor of Health Sciences and Chair of the Department of Health Sciences is the past recipient of an Established Investigator of the American Heart Association. Dr. Morgan has served as a standing member of study sections at NIH and AHA. She directs a Program Project “Dynamics of the Vascular Smooth Muscle Cytoskeleton” and is the leader of a component project on “Plasticity of the Smooth Muscle Cytoskeleton”. She has served as an Associate Editor for the American Journal of Physiology: Cell Physiology and on numerous editorial boards. Her research interest is an integrated understanding of the interaction of signaling pathways with the cytoskeleton in contractile smooth muscle cells and the role of those interactions in the regulation of vascular tone and aortic stiffness.
- Min J, Reznichenko M, Poythress P, Gallant C, Vetterkind S, Li Y, Morgan KG. Src Modulates Contractile Vascular Smooth Muscle Function via Regulation of Focal Adhesions. J Cell Physiol. 2012; 227: 3585-92.
- Baranwal S, Naydenov NG, Harris G, Dugina V, Morgan KG, Chaponnier C, Andrei I. Ivanov AI. Non-redundant roles of cytoplasmic beta- and gamma-actin isoforms in regulation of epithelial apical junctions. MBoC 2012; 23:3542-53.
- Yilmaz M, Gangopadhyay SS, Leavis P, Grabarek Z, Morgan KG. Phosphorylation at Ser26 in the ATP binding site of Calcium Calmodulin dependent Kinase II as a mechanism for switching off the kinase activity. Bioscience Reports 2013; 33: (2),art:e00116.doi:10.1042.
- Saphirstein RJ, Gao YZ, Jensen MH, Gallant CM, Vetterkind S Moore JR, Kathleen G. Morgan KG. The Focal Adhesion: A Regulated Component of Aortic Stiffness. PLoS One 2013; 8:e62461
- Poythress RH, Gallant C, Vetterkind S, Morgan KG. Vasoconstrictor-induced endocytic recycling regulates focal adhesion protein localization and function in vascular smooth muscle. Am J Physiol Cell Physiol. 2013; 305:C215-27.
- Vetterkind S, Poythress RH, Lin QQ, Morgan KG. Hierarchical scaffolding of an ERK1/2 activation pathway. Cell Communication and Signaling. 2013; 11:65.
Dr. Naya has interests in the areas of cardiac development and disease, muscular dystrophy, mouse developmental biology, and gene regulation.
Find Dr. Naya at the Department of Biology website.
- McCalmon SA, Desjardins D, Ahmad S, Davidoff K, Snyder CM, Sato K, Ohashi K, Kielbasa O, Mathew M, Ewen EP, Gavras H, Walsh K, Naya FJ. (2010). Modulation of angiotensin II-mediated cardiac remodeling by the MEF2A target gene Xirp2. Circ Res. 106(5):952-60.
- Reynolds JG, McCalmon SA, Donaghey JA, Naya FJ. (2008). Deregulated PKA signaling and myospryn expression in muscular dystrophy. J Biol Chem, 283(13):8070-4.
- Reynolds JG, McCalmon SA, Tomczyk T, Naya FJ. (2007). Identification and mapping of protein kinase A binding sites in the costameric protein myospryn. Biochim Biophys Acta. 1773(6), 891-902.
- Parsons SA, Millay DP, Sargent MA, Naya FJ, McNally EM, Sweeney HL, Molkentin JD. (2007). Genetic disruption of calcineurin improves skeletal muscle pathology and cardiac disease in a mouse model of limb-girdle muscular dystrophy. J Biol Chem. 282(13), 10068-78.
- Huang HT, Brand OM, Mathew M, Ignatiou C, Ewen EP, McCalmon SA, Naya FJ. (2006). Myomaxin is a novel transcriptional target of MEF2A that encodes a Xin-related alpha-actinin-interacting protein. J Biol Chem; 281(51), 39370-9.
- Durham JT, Brand OM, Arnold M, Reynolds JG, Muthukumar L, Weiler H, Richardson JA, Naya FJ. (2006). Myospryn is a direct transcriptional target for MEF2A that encodes a striated muscle, alpha-actinin-interacting, costamere-localized protein. J Biol Chem. 281(10), 6841-9.
A professor of Medicine and Biochemistry and Adjunct Professor of Pharmacology and Experimental Therapeutics, the Scientific Director of the Central Transgenic Facility, and the Founding Director of the Evans Center for Interdisciplinary Biomedical Research (Evans Center) at Boston University School of Medicine, is a recipient of several awards, such as from the American Heart Association, NIH and Weizmann Institute. Dr. Ravid has served on review panels for both agencies and is a member of the Editorial Board of few journals. She is the co-author and editor of two scientific books related to her expertise in gene regulation coupled to cell cycle control in the hematopoietic system. Her research focuses on the genetic and signaling mechanisms regulating the development of hematopoietic stem cells into the platelet lineage, as well as on the role of adenosine receptors in vascular and platelet function. Her studies on gene targeting to platelets of transgenic mice, or adenosine receptor gene deletions for the purpose of gene manipulation and gene therapy bear on the pathophysiology of atherosclerosis, and have attracted great attention.
–More information on Dr. Ravid, including a list of her publications, can be found in: http://www.bumc.bu.edu/ravidlab/
and in: http://profiles.bu.edu/Katya.Ravid
–Information on the Evans Center can be found in: http://www.bumc.bu.edu/evanscenteribr/
Nelson Ruiz-Opazo, Ph.D.
A professor of medicine, is fellow of the AHA Councils of Arteriosclerosis and Basic Science, and former member of the AHA National Molecular Signaling I study committee. He serves as reviewer for NIH special review study sections and was a past AHA Established Investigator. His research program focuses on an integrated molecular-genetic analysis of essential hypertension and associated target organ complications (i.e.: renal disease, cardiac hypertrophy and vascular cognitive impairment) using classical genetics and related genomic approaches. His studies include genetic rat models of essential hypertension and spatial learning and memory. His research also includes genetic association studies in selective human populations. The molecular characterization of novel angiotensin II, vasopressin and endothelin receptors in his laboratory has provided additional bases for ongoing investigation of their respective physiologic and pathophysiological roles in cardiovascular and neurobiological functions such as in learning and memory. These focused studies are complemented with classical QTL (quantitative trait locus) analysis and congenic rat development that are currently being performed to identify QTGs (quantitative trait genes) influencing blood pressure, cardiac hypertrophy, renal disease and learning and memory. Together with Dr. Victoria L. M. Herrera, Dr. Ruiz-Opazo has pioneered the production of transgenic rat models at BUSM.
Una Ryan, Ph.D.
O.B.E., Research Professor of Medicine, is President and Chief Executive Officer of AVANT Immunotherapeutics, Inc., a publicly traded Massachusetts biotechnology company engaged in the discovery, development, and commercialization of products that harness the human immune system to prevent and treat disease. She is a past president of the Council on Cardiopulmonary and Critical Care of the American Heart Association. She was formerly Chairman of Pathology A, a Study Section of the NHLBI, and has served on numerous NIH and AHA review and advisory committees. She is the recipient of an NIH MERIT Award, was an Established Investigator of the AHA, and was a Howard Hughes Investigator. Dr. Ryan currently serves on the Boards of both the Biotechnology Industry Organization and the Massachusetts Biotechnology Council, as well as the Whitehead Institute Board of Associates, and is an organizer of the NATO Advanced Study Institute. In 2002 Her Majesty Queen Elizabeth II awarded Dr. Ryan the Order of the British Empire (OBE) for her services to research, development and promotion of biotechnology.
Flora Sam M.D., FACC, FAHA; Associate Professor of Medicine
Dr. Sam is a cardiologist and Associate Professor of Medicine at Boston University School of Medicine. She is a Fellow of the American College of Cardiology (FACC), and American Heart Association (FAHA). She is board certified in Internal Medicine, Cardiovascular Diseases, and Advanced Heart Failure/Transplant Cardiology. She joined the cardiovascular faculty at Boston Medical Center in 2000 and is an integral part of the Cardiomyopathy/Heart Failure Program. Dr. Sam is a specialist in heart failure and cardiomyopathies. She was a Committee Member of 2013 American College of Cardiology Foundation / American Heart Association Guideline for the Diagnosis and Management of Heart Failure in Adults. Dr. Sam is a physician scientist and was elected as a member of the American Society of Clinical Investigation (ASCI) in 2011. Dr. Sam is a grant reviewer for the American Heart Association (AHA), NIH and VA study sections. Dr. Sam was a recipient of a NIH Research Career Development Award K23 and AHA grant award, and is currently the Principal Investigator on NIH-sponsored R01 grants. She has also been the recipient of industry funded awards. Dr. Sam investigates mechanisms of adverse myocardial remodeling in cardiac hypertrophy, cardiomyopathies and heart failure, particularly diastolic heart failure. Dr. Sam’s dual research focus (animals and humans) has permitted her to use the clinical findings from her clinical heart failure practice to develop new and testable hypotheses for basic investigation. Her research is translational and encompasses in vitro cell culture experiments, in vivo genetically modified mice and human subjects with heart failure and cardiomyopathies.
- Essick EE, Wilson RM, Pimentel DR, Shimano M, Baid S, Ouchi N, Sam F. Adiponectin Modulates Oxidative Stress-induced Autophagy in Cardiomyocytes. PLOS One 2013;8:e68697
- Tanaka K, Essick EE, Doros G, Tanriverdi K, Connors LH, Seldin DC, Sam F. Circulating Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Cardiac Amyloidosis. J Am Heart Assoc. 2013 Mar 12;2(2):e005868.
- Garcia AG, Wilson RM, Heo J, Murthy NR, Baid S, Ouchi N, Sam F. Interferon-γ Ablation Exacerbates Myocardial Hypertrophy in Diastolic Heart Failure. Am J Physiol Heart Circ Physiol. 2012;303:H587-96
- El-Armouche A, Ouchi N, Tanaka K, Doros G, Wittköpper K, Schulze T, Eschenhagen T, Walsh K, Sam F. Follistatin-like 1 in Chronic Systolic Heart Failure: A Marker of Left Ventricular Remodeling. Circ Heart Fail. 2011;4:621-7.
- Sam F, Duhaney T.S, Sato K, Wilson RM, Ohashi K, Sono-Romanelli S, Higuchi A, De Silva DS, Qin F, Walsh K, Ouchi N. Adiponectin Deficiency, Diastolic Dysfunction and Diastolic Heart Failure. Endocrinology. 2010;151:322-31.
- Wilson RM, De Silva DS, Sato K, Izumiya Y, Sam F. Effects of Fixed-Dose Isosorbide Dinitrate/Hydralazine on Diastolic Function and Exercise Capacity in Hypertension-Induced Diastolic Heart Failure. Hypertension, 2009;54:583-90.
Dr. Seta is an Assistant Professor of Medicine in the Vascular Biology Section. Her major research interests are arterial stiffness, aortic remodeling and hypertension. Arterial stiffness is a vascular condition characterized by impaired endothelial function and aortic remodeling resulting in loss of elasticity of large blood vessels and it has recently emerged as an independent risk factor for cardiovascular events. Dr. Seta’s lab showed that arterial stiffness develops rapidly in a model of diet-induced obesity, which mimics the human metabolic syndrome. We focus on the discovery of novel therapeutic targets and life-style interventions that can prevent or reverse arterial stiffness and its deleterious complications, including hypertension, particularly in settings of obesity and insulin-resistance. The laboratory optimized innovative in vivo and in vitro approaches to measure arterial stiffness and active and passive properties of blood vessels. Among others, we use high-resolution ultrasound echocardiography, radiotelemetry and high-fidelity pressure catheters, to assess arterial stiffness, blood pressure and cardiac and arterial functions. In addition, Dr. Seta’s laboratory investigates the molecular mechanisms of aortic dissection and aneurysm, two deadly cardiovascular conditions affecting the aorta for which, currently, there are no pharmacological treatments. For more informations on Dr. Seta, please visit:
Donald M. Small, M.D.
A professor of physiology and biophysics, biochemistry and medicine, and Chairman of the Department of Physiology and Biophysics, has received the Distinguished Achievement Award and the William Beaumont Prize of the American Gastroenterological Association and the Eppinger Prize for his now-classical work on bile and gallstone formation. Dr. Small was Chairman of the AHA’s Council on Arteriosclerosis and George Lyman Duff Lecture in 1986 and an elected member of the Association of American Physicians, the American Society for Clinical Investigation, and the American Society of Biological Chemists. He currently is a member of the editorial boards of Arteriosclerosis, Thrombosis and Vascular Biology and is an editor of Current Opinions in Structural Biology, (Lipids) and Chairman of the Advisory Board of Journal of Lipid Research.
Deborah A. Siwik, Ph.D., is a Research Assistant Professor in the Whitaker Cardiovascular Institute, and the Lab Director of the Myocardial Biology Unit. She received her Ph.D. in Pharmacology from the University of Illinois at Chicago and her post-doctoral training at Brigham and Women’s Hospital and Harvard Medical School and at Boston University.
- EMMPRIN Mediates Beta-Adrenergic Receptor-Stimulated Matrix Metalloproteinase Activity in Cardiac Myocytes. Siwik DA, Kuster GM, Brahmbhatt JV, Zaidi Z, Malik J, Ooi H, Ghorayeb G, 2008. J Mol Cell Cardiol 44(1)210-217.
- Relations of Matrix Remodeling Biomarkers to Blood Pressure Progression and Incidence of Hypertension in the Community. Dhingra R, Pencina MJ, Schrader P, Wang TJ, Levy D, Meigs J, Pencina K, Sundstrom J, Siwik DA, Colucci WS, Benjamin EJ, Vasan RS, 2009. Circulation 119(8):1101-1107.
- Venkatesan B, Reddy VS, Valente A, Siwik DA, Chandrasekar B, 2009. Resveratrol Blocks Interleukin-18-EMMPRIN Crossregulation and Smooth Muscle Cell Migration. . Am J Physiol (Heart Circ Physiol) 297(2):H874-886.
- Biolo A, Fisch F, Balog J, Chao T, Schulze PC, Ooi H, Siwik DA, Colucci WS, 2010. Episodes of Acute Heart Failure Syndrome are Associated with Increased Levels of Troponin and Extracellular Matrix Markers. Circ Heart Failure 3(1):44-50.
- Velagaleti RS, Gona P, Sundström J, Larson MG, Siwik D, Colucci WS, Benjamin EJ, Vasan RS, 2010. Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality. Arterioscler Thromb Vasc Biol. 30(11):2283-8
Richard Wainford, Ph.D.
Dr Wainford obtained a Bachelors in Zoology from the University of Wales, Cardiff in 1999. Dr Wainford undertook his Graduate training in the Laboratory of Molecular Pharmacology and Toxicology in the Department of Medicine and Therapeutics at the University of Aberdeen School of Medicine under the guidance of Professor Hawksworth, earning a PhD in Molecular Pharmacology in 2004. Dr. Wainford then completed a 2-year post-doctoral fellowship in the Department of Pharmacology at the Louisiana State University Health Sciences Center in New Orleans in Cardiovascular & Renal Pharmacology under the mentorship of Dr. Kapusta. Dr. Wainford then became an Instructor of Pharmacology in 2008, remaining in the laboratory of Dr. Kapusta until his promotion to the rank of Assistant Professor in 2010. Dr. Wainford joined the Department of Pharmacology & Experimental Therapeutics at the Boston University School of Medicine and the Whitaker Cardiovascular Institute in 2011 as an Assistant Professor.
2008 American Physiological Society Donald Reis Research Recognition Award
2009 American Heart Association Beginning-Grant-In-Aid
2010 NCRR COBRE Independent Mentored Scientist Award
2011 NHLBI R01 “Brain Gα-subunit protein mediated neural control of blood pressure”
2011 American Physiological Society Research Career Enhancement Award
2011 International Society of Hypertension Best Poster Award at the 2011 AHA Council on High Blood Pressure Meeting
2012 Dean Franklin Young Investigator Award
- Wainford, R.D., Kapusta, D.R. (2010) Hypothalamic paraventricular nucleus Gαq sub-unit protein pathways mediate vasopressin dysregulation and fluid retention in salt-sensitive rats. Endocrinology. 151: 5403-5413.
- Wainford, R.D., Kapusta, D.R. Functional selectivity of central Gα-subunit proteins in the cardiovascular and renal excretory responses evoked by central α2-adrenoceptor activation in vivo. British Journal of Pharmacology. 2011. doi: 10.1111/j.1476-5381.2011.01662.x
- Tadashi, TK, Sukinov S, Wainford RD, Kapusta DR, Delafontaine P. AngiotensinII reduces food intake by altering orexigenic neuropeptide expression in the mouse hypothalamus. Endocrinology 2012 In Press
Dr. Wong’s research has been funded by NIH, NASA, DOE, and industry. Awards she has received include a NSF CAREER Award (2000), Clare Boothe Luce Assistant Professorship (1998-2003), Dupont Young Professor Award (2004). She was elected to the American Institute for Medical and Biological Engineering, AIMBE (2009), and received a Hartwell Individual Biomedical Research Award (Class of 2009). She was also selected for participation in the National Academy of Science Frontiers in Engineering (2001), National Academies Keck Futures Initiative Conference (2003), German-American Frontiers in Polymer Science (2003), and Japan-America Frontiers in Engineering (2004). Dr. Wong has served as Associate Director of the Center for Nanoscience and Nanobiotechnology (2006-2008) and Associate Chair for Graduate Studies (2006-2010) in Biomedical Engineering at Boston University.
- Williams, C., X.Q. Brown, E. Bartolak-Suki, H. Ma, A. Chilkoti, and J.Y. Wong (2011) “The use of micropatterning to control smooth muscle myosin heavy chain expression and limit the response to transforming growth factor beta-1 in vascular smooth muscle cells,” Biomaterials, 32: 410-418.
- Brown, X., E. Bartolak-Suki, C. Williams, M. Walker, V.M. Weaver, and J.Y. Wong (2010) “Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: Implications for atherosclerosis,” Journal of Cellular Physiology, 225(1): 115-122. Duncanson, W.J., K. Oum, J.R. Eisenbrey, R.O. Cleveland, M.A. Wheatley, and J.Y. Wong (2010) “Targeted binding of PEG-lipid modified polymer ultrasound contrast agents with tiered surface architecture,” Biotechnology and Bioengineering, 106(3): 501-506.
- Isenberg, B.C.*, P.A. DiMilla*, M. Walker, S. Kim, and J.Y. Wong (2009) “Vascular smooth muscle cell durotaxis depends on substrates stiffness gradient strength,” Biophys. J., 97: 1313-1322.
- Williams C.L., Y. Tsuda, B.C. Isenberg, M. Yamato, T. Shimizu, T. Okano, and J.Y. Wong (2009) “Aligned cell sheets grown on thermo-responsive substrates with micro-contact printed protein patterns,” Advanced Materials, 21(21): 2161-2164.
- Isenberg, B.C., Y. Tsuda, C. Williams, T. Shimizu, M. Yamato, T. Okano, and J.Y. Wong (2008) “A thermoresponsive, microtextured substrate for cell sheet engineering with defined structural organization,” Biomaterials, 29(17): 2565-72.
Vassilis I. Zannis obtained his PhD in biochemistry from UC Berkeley, USA and received postdoctoral training in sciences at the University of California at San Francisco Medical School, MIT and Harvard Medical School, where he also served for two years as an Assistant Professor. He was recruited to Boston University in 1984 where he established the Section of Molecular Genetics. Currently he is Professor of Medicine/Biochemistry and Director of Molecular Genetics at Boston University School of Medicine. He also served from 1986 to 2007 as a Visiting Professor at the University of Crete Medical School, where he focused in the development of research programs and the creation of an MD-PhD program, and a medical student exchange program between Boston University and the University of Crete.
- Zannis, V.I., P.W. Just, and J.L. Breslow. 1981. Human apolipoprotein E isoprotein subclasses are genetically determined. Am. J. Hum. Genet. 33:11-24. PM:7468588
- Cladaras, C., M. Hadzopoulou-Cladaras, R.T. Nolte, D. Atkinson and V.I. Zannis. 1986. The complete sequence and structural analysis of human apolipoprotein B-100: Relationship between apoB-100 and apoB-48 forms. The EMBO J. 5:3495-3508. PM:3030729
- Chroni, A., T. Liu, I. Gorshkova, H.-Y. Kan, Y. Uehara, A. von Eckardstein, V.I. Zannis. 2003. The central helices of ApoA-I can promote ATP-binding cassette transporter A1 (ABCA1)-mediated lipid efflux. Amino acid residues 220-231 of the wild-type ApoA-I are required for lipid efflux in vitro and high density lipoprotein formation in vivo. J. Biol. Chem. 278:6719-6730. PM:12488454
- Kypreos, K.E., K.W. van Dijk, L.M. Havekes, V.I. Zannis. 2005. Generation of a recombinant apolipoprotein E with improved biological functions. J. Biol. Chem. 280:6276-6284. PM:15576362
- Drosatos, K., D. Sanoudou. K.E. Kypreos, D. Kardassis, V.I.Zannis. 2007. A dominant negative form of the transcription factor c-Jun affects genes that have opposing effects on lipid homeostasis in mice. J. Biol. Chem. 282:19556-19564. PM:17456467
- Sanoudou, D., A. Duka, K. Drosatos, K.C. Hayes, V.I. Zannis. 2009. Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human apoA-I transgenic mice. Pharmacogenomics J. 10:165-179. PM:19949424