San Diego State University - Minds that move the world

Meet Dr. Sussman

   
Dr. Mark Sussman is a tenured Professor of Biology at San Diego State University and key investigator at the San Diego State University Heart Research Institute. Upon completing his doctoral thesis at the University of Southern California where he studied viral immunology in 1989, Dr. Sussman entered myocardial research though postdoctoral studies in cytoskeletal biology characterizing the role of the actin filament capping protein tropomodulin in heart under the mentorship of Dr. Larry Kedes. In 1995, Dr. Sussman accepted a position as Assistant Professor in the Division of Molecular and Cardiovascular Biology at Children’s Hospital Medical Center in Cincinnati, Ohio. Building upon his postdoctoral work, Dr. Sussman created the first mouse model of dilated cardiomyopathy, which exhibited myofibril organizational defects resulting from cardiac-specific transgenic overexpression of tropomodulin. Over his ensuing eight year tenure at Children’s Hospital, his lab completed more than a dozen published studies examining the multiple facets of the pathogenesis of dilation in the tropomodulin mouse model including calcium handling abnormalities, cytoskeletal defects, and altered signal transduction. Additional studies on myocardial signal transduction involving the small GTPase rac1 produced another murine model of cardiomyopathy and prompted Dr. Sussman to examine molecular interventional strategies to inhibit the progression of dilation and heart failure. Intrigued by prevailing paradoxical observations in published literature linking the cardioprotective kinase Akt/PKB to heart failure in transgenic mouse models, Dr. Sussman found nuclear accumulation of Akt/PKB in response to anti-apoptotic stimuli. These seminal observations led to Dr. Sussman’s pioneering studies relating Akt/PKB and gender as he demonstrated myocardial differences between the sexes in Akt/PKB nuclear accumulation that stem from estrogenic stimuli. This finding was the genesis of his pivotal contribution to survival signaling networks in heart: targeting of Akt/PKB to the cardiomyocyte nucleus affords cardioprotection without deleterious hypertrophic consequences. Fusing his ongoing studies of cardioprotection together with his background in cytoskeletal biology, Dr. Sussman expanded his studies of nuclear Akt/PKB biology to include novel associations with LIM domain proteins that shuttle through the nucleus. His current Akt/PKB-related research involves the surprising effects of nuclear Akt/PKB signaling for cardiomyocytes including anti-hypertrophic signaling, induced downstream mediators of cell survival including Pim-1 kinase, and the potentiation of survival and regenerative capacity for cardiac stem cells. These studies have been published in high impact journals including the Journal of Clinical Investigation, Proceedings of the National Academy of Sciences, and most recently Nature Medicine.
Repairing and restoring myocardial structure and function represents the ideal outcome for treatment of cardiomyopathy. Current therapeutic interventions rely predominantly upon pharmacologic strategies to slow the progression of heart failure, but the ultimate destination for many of these patients will be an operating room where they will receive a mechanical assist device or a transplanted donor heart. The cost, invasiveness, shortage of suitable donor organs, and compromised quality of life are just a few of the many issues stemming from the current approaches to treatment of heart failure. An attractive alternative vision for these patients would be the use of repair processes that, rather than prop up and maintain damaged organ function, would enable the replacement and repair of the compromised tissue on a cellular level. Over the past decade a concerted effort by scientists and clinicians has advanced the use of gene therapy as an approach to treatment of heart failure. These studies have shown that genetic reprogramming of the myocardium can be used to prevent cell death, inhibit maladaptive remodeling, enhance hemodynamic function, promote angiogenesis, and block deleterious signaling. Although gene therapy approaches remain a popular avenue for delineating the role of proteins in cardiac repair and rescue, many practical aspects of gene therapy such as delivery and targeted expression in the myocardium, regulation of gene expression, and persistence of expression have hampered implementation of myocardial gene therapy for treatment of heart failure. However, recent discoveries related to regeneration and repair of the myocardium using stem cells have shifted the paradigm of treatment for myocardial disease. Discoveries linking stem cell-based therapies to improvements in myocardial performance have invigorated the field, but current limitations in stem cell-based approaches present significant barriers. Dr. Sussman’s research concentrates upon existing challenges in stem-cell based treatment and how these may be overcome by incorporation of gene therapy, resulting in a combinatorial approach that uses genetic engineering to potentiate stem cell activity for myocardial repair.
Dr. Sussman’s research has been supported by grant awards from the National Institutes of Health and the American Heart Association since establishing his independent laboratory in 1995. He was recognized as an Established Investigator of the National American Heart Association in 2000. Currently, Dr. Sussman serves on multiple leadership and review committees for the American Heart Association at both affiliate and national organization levels. He has authored over 75 peer-review articles and is a popular speaker at national and international venues with over 100 invited presentations in the last 15 years. Dr. Sussman also served as Chair of the study section for Cardiac Contractility, Hypertrophy, and Heart Failure at the National Institutes of Health from as well as a standing member of editorial boards for several journals including Circulation Research, the Journal of Biological Chemistry, the American Journal of Physiology (Heart and Circulatory Physiology), Regenerative Medicine, and the Journal of Molecular and Cellular Cardiology. His laboratory at San Diego State University serves as a training ground for undergraduate, masters and doctoral students, and postdoctoral trainees who are now mentored under Dr. Sussman’s guidance. Recently, he has championed efforts to bring together cardiovascular researchers in the San Diego academic community with a collaborative research Program Project Grant that will pool knowledge and resources to further studies on the molecular and cellular basis of heart failure – the first award of its kind for any California State University campus.