Ivor J. Benjamin MD, FAHA, FACC, is Professor of Medicine at Froedtert Hospital and the Medical College of Wisconsin. A board-certified specialist and consultant in internal medicine and cardiology, Dr. Benjamin’s clinical interests are general cardiology, inheritable heart failure, and myocardial infarction.
Dr. Benjamin received his medical degree from the Johns Hopkins University School of Medicine in Baltimore, MD. He received training in internal medicine at Yale-New Haven Hospital and cardiology fellowship training at Michael Reese Hospital (University of Chicago).
In the past, Dr. Benjamin served as the Division Chief of Cardiology at the University of Utah (2003-2009) and Chair of the Board of Scientific Counselors at the National Heart Lung and Blood Institutes (NHLBI). He is a member of the American Society of Clinical Investigation, American Association of Physicians, a Fellow of the American Heart Association, Fellow of the American College of Cardiology, and serves on the National Advisory Board of the NHLBI.
Our laboratory focuses on the pathogenic mechanisms involving selected stress response pathways (e. g., heat shock response, redox state) induced at onset of disease and their subsequent dysregulation culminating in disease progression. We are specifically interested in deciphering the genetic, molecular and metabolic events that promote adverse remodeling in response to acquired conditions (e.g., heart attacks) and inheritable (e.g., cardiomyopathy) disorders. From such insights of the causal mechanisms using complementary model systems (i.e., yeast, flies, mice), our multidisciplinary program and translational studies are seeking to exploit innovative strategies (e.g., small molecule targeting, cell regeneration) for diagnostic, therapeutic, and ultimately disease prevention.
Work in our laboratory focuses on three complementary themes linked to protein misfolding diseases:
Small heat shock proteins (sHSPs) and heart failure.
Alzheimer’s disease is a well-known protein misfolding disorder but few research scientists recognize that heart failure shares similar pathogenic mechanism(s). Our longstanding interests in the roles of small HSPs, which double as molecular chaperones, are focusing on what mechanisms govern the fate by which acquired (e.g., heart attacks) and/or inherited (e.g., hypertrophic cardiomyopathy) conditions lead to heart failure. Using transgenic and knockout mouse technology, this line of investigation might explain how chaperone-like functions of HSPs might ultimately be exploited therapeutically to speed the physiological recovery in tissues damaged after a heart attack.
Redox biology and gain of 'toxic' function mechanisms in aggregation-prone diseases.
Many results of numerous antioxidants in clinical trials have failed to show therapeutic benefits. We have recently discovered a new disease mechanism: “reductive stress” that challenges the existing paradigm of oxidative stress. In transgenic mice recapitulating a protein-misfolding cardiomyopathy associated with myofibrillar disease in humans, we have demonstrated that decreasing the function of glucose-6-phosphate dehydrogenase (G6PD), an antioxidant that generates the reductant NADPH, “cures” the disease in mice by ameliorating reductive stress, aggresome formation, hypertrophy, heart failure and death. Ours collaborative studies in complementary model systems (e.g., flies, yeast, mice) are seeking to identify other disease-causing mutations and their potential interacting pathways that either increase resistance and/or decrease susceptibility in disease pathogenesis.
Stem and human iPSCs for cellular regeneration.
Development of human induced pluripotent stem cells (iPSCs) derived from adult somatic cells entirely circumvents usage of embryonic stem cells. We are testing the hypothesis that the pathogenic transition of cardiac and neurodegenerative diseases are causally related to dysregulation of stress response and anti-oxidative pathways, linked to macromolecular damage, in adult stem and progenitor cells. After recent sabbatical training at the Mass General Hospital/Harvard Stem Cell Institute and Gladstone Institute for Cardiovascular Research/UCSF, Dr. Benjamin and colleagues are pursuing investigations 1) to understand redox-signaling mechanisms influencing cardiac differentiation in human iPSC and 2) to model disease-specific iPSCs from patients with myofibrillar disease. To achieve the latter aim, we are seeking collaborators to establish an international consortium for modeling rare myofibrillar and related diseases using our iPSC platform technology.
Graduate students and postdoctoral trainees can select from, but are not limited to these ongoing projects in the Benjamin laboratory.
Available Graduate Student and Postdoctoral Research Positions
Graduate Students and Postdoctoral Research Associate positions are available in induced pluripotent stem cells (iPSC), protein misfolding, redox biochemistry, and stress response pathways. (Read More)
Cardiologist Ivor J. Benjamin, MD, receives the prestigious NIH 2009 Pioneer Award. This $2.5 million award will allow Dr. Benjamin and his laboratory team and colleagues to research how "reductive stress" may damage the heart and other organs. Read the September 24, 2009 News Article.