Ivor J. Benjamin, M.D., FACC, FAHA

Research Interests

  • Reductive Stress
  • Heat Shock Proteins
  • aB-crystallin (hR120GCryAB)
  • Ischemia/Reperfusion
  • Oxidative Stress
  • Protein Aggregation Cardiomyopathy
  • Genetics
  • glucose 6-phosphate dehydrogenase (G6PD)

Languages

  • English

Academic Information

  • Departments: Biochemistry - Adjunct Professor

Board Certification

  • American Board of Internal Medicine (Sub: Cardiovascular Disease)
  • American Board of Internal Medicine (Internal Medicine)

Academic Office Information

  • (801) 585-7676
  • School of Medicine
    Division of Cardiology
    30 N 1900 E, Room: 4A100
    Salt Lake City, UT 84132

Research Statement

Protein aggregation cardiomyopathy (PAC) (also termed desmin-related myopathy--DRM) is a life-threatening presentation of a multisystem disease caused by the exchange mutation in the gene encoding the human small HSP aB-crystallin (hR120GCryAB). Our major goal is to understand the pathogenic mechanisms by which hR120CCryAB expression causes cardiotoxicity and heart failure. Recent genetic studies in mice have shown that selective hR120GCryAB expression in the heart induces a novel toxic gain-of-function mechanism linked to increased activity of glucose 6-phosphate dehydrogenase (G6PD) mimicking reductive stress. Reductive stress refers to an abnormal increase of reducing equivalents (e.g., glutathione, NADPH), which has been demonstrated in lower eukaryotes but uncommonly in mammals and/or disease states. [Rajasekaran et. al, 2007, PDF].

Genetic evidence, that dysregulation of G6PD activity is a causal mechanism for R120GCryAB cardiomyopathy, raises several important questions and provides the thematic platform for programmatic support and research collaborations. What novel interactions between mutant CryAB and G6PD contribute to the pathogenesis of cardiomyocyte toxicity in R120GCryAB cardiomyopathy? Are other interacting factors necessary and sufficient for toxic gain-of-function mechanism in R120G cardiac disease? What the molecular mechanisms and signaling pathways that contribute to increased G6PD activity? Does reductive stress exert direct or indirect consequences on mitochondrial (dys)function? What changes in gene expression occur before the onset of detectable myopathic or pathologic alterations, and how does redox imbalance regulate gene expression?

Graduate and postdoctoral trainees can select from but are not limited to a number of ongoing projects in the laboratory. We are assessing all presently know disease-causing CryAB mutants for their capacity to induce protein aggregation and reductive stress in vitro. From such analysis, our investigative team would have compiled a broad but horizontally based platform, which, by design, will be integrated vertically with physical biochemistry and structural studies, mitochrondrial energetics and metabolic studies, and biophysical analysis of arrhythmogenesis using R120GCryAB as a prototype.

Academic Bio

Ivor J. Benjamin, M.D. is Director of the University of Utah's Laboratory of Cardiac Disease, Redox Signaling and Cell Regeneration. Dr. Benjamin’s clinical interests are inheritable cardiomyopathies, skeletal and cardiac myofibrillar diseases, heart failure, and the regenerative medicine. He splits his time between laboratory work and clinical work at both the University of Utah Hospital and the Salt Lake City VA Hospital. From 2003 to 2009, he was the Division Chief of Cardiology and second individual to hold the Christi T. Smith Endowed Chair in Cardiology Research at the University of Utah. As the Christi T. Smith Endowed Chair and Division Chief, Dr. Benjamin prioritized building and enhancing the Division of Cardiology and fostering the translation of basic cardiovascular research into the clinic at the University of Utah Health Sciences Center.

Dr. Benjamin received his B.A. from Hunter College at the City University of New York in 1978 and his M.D. from the Johns Hopkins University School of Medicine in 1982. He completed a Residency in Internal Medicine at Yale-New Haven Hospital, Yale University School of Medicine in 1985, and a Cardiology Fellowship at the Cardiovascular Institute, Michael Reese Hospital and Medical Center, University of Chicago in 1988. Dr. Benjamin completed an AHA-Bugher Fellowship in Molecular Cardiology at the University of Texas Southwestern Medical Center at Dallas (1990-1992). A recipient of the Established Investigator award from the American Heart Association, Dr. Benjamin has been continuously funded from both private foundations and the National Institutes of Health for over 15 years. In 1999, Dr. Benjamin was elected into the American Society of Clinical Investigation and, in 2005, into the Association of American Physicians. In 2009, he was awarded the prestigious NIH Director's Pioneer Award of $2.5 million, which Dr. Benjamin has put towards his laboratory's research of "reductive stress."

Prior to coming to the University of Utah, he served as Professor of Medicine and Education Program Coordinator of the Donald Reynolds Cardiovascular Center at the University of Texas Southwestern Medical Center in Dallas, TX from 2002 – 2003. Dr. Benjamin has been honored for his scientific contributions and received the Ken Bowman Research Achievement Award from the University of Manitoba.

Dr. Benjamin has been active in several medical societies including service as President of the Dallas Division of Texas Affiliate, American Heart Association (2001-2002), a member of the Task Force on Council Resources, American Heart Association (1998-present), the Chair of the Scientific Publishing Committee (2005-2007), American Heart Association (2001-2005), and Vice President, Council for Basic Cardiovascular Sciences, American Heart Association (2003-2004). He has served in a number of capacities in national organizations including an appointment to the NHLBI Board of Scientific Counselors. Dr. Benjamin has a life-long commitment to mentorship and medical education. He has served on the Scientific Board and Board of the Stanley Sarnoff Cardiovascular Research Foundation. He is actively engaged in internantional research collaboration with Leducq Foundation Transatlantic Network of Excellence. As a distinguished medical educator, he currently serves as the Editor-in-Chief of Andreoli and Carpenter’s Essentials of Medicine (Elsevier Press).

For anyone with career aspirations in the biomedical sciences, you are welcome to visit our lab's webpage http://medicine.utah.edu/internalmedicine/cardiology/research/benjaminlab.php. Our laboratory welcomes trainees at all levels (graduate students, medical students and postdoctoral clinical or basic research fellows) to join our multidisciplinary investigative team.

Education History

Type School Degree
Research Fellow University of Texas Southwestern Medical Center
Molecular Biology
Research Fellow
Research Fellow Duke University Medical Center
Molecular Cardiology
Research Fellow
Fellowship Michael Reese Hospital (University of Chicago)
Cardiovascular Diseases
Fellow
Residency Yale University School of Medicine
Internal Medicine
Resident
Internship Yale University School of Medicine
Internal Medicine
Intern
Professional Medical Johns Hopkins University
Medicine
M.D.
Research Fellow Johns Hopkins University
Research Fellow
Undergraduate Hunter College (Thomas Hunter Honors Program)
B.A.

Selected Publications

Journal Article

  1. HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice.Ishiwata T, Orosz A, Wang X, Mustafi SB, Pratt GW, Christians ES, Boudina S, Abel ED, Benjamin IJ (2012). HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice. PLoS One, 7(8), e42118.
  2. Glutathione-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity.Zhang H, Limphong P, Pieper J, Liu Q, Rodesch CK, Christians E, Benjamin IJ (2012). Glutathione-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity. FASEB J, 26(4), 1442-51.
  3. Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR.Gabai VL, Meng L, Kim G, Mills TA, Benjamin IJ, Sherman MY (2012). Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR. Mol Cell Biol, 32(5), 929-40.
  4. Heng B Xie HB, Cammarato A, Suggs JA, Lin H-C, Bernstein SI, Benjamin IJ, Golic KG (In Review). NADPH Metabolic Network regulates human ¿B-crystallin cardiomyopathy and reductive stress in Drosophila melanogaster. #Corresponding authors. PLoS Genet.
  5. Limphong P, Zhang H, Liu Q, Christians E, Riedel M, Ivey K, Cheng P, Taylor G, Winge D, Srivastava D, Benjamin IJ (In Revision). Modeling Protein Aggregation Cardiomyopathy using Murine Induced Pluripotent Stem Cells. Stem Cells.
  6. Zhang H, Liu Q, Limphong P, Wende A, Wang X, Zhang X, Pratt GW, Schubert HL, Hill CP, Christians E, Benjamin IJ (In Review). Cataract-related Human CryAB Mutation Associated with Protein Aggregation Spares the Development of Desmin-related Cardiomyopathy in Mice. J Mol Cell Cardiol.

Review

  1. Proteostasis and REDOX state in the heart.Christians ES, Benjamin IJ (2012). Proteostasis and REDOX state in the heart. [Review]. Am J Physiol Heart Circ Physiol, 302(1), H24-37.

Book Chapter

  1. Ivor J Benjamin (11/2012). Heart Failure in the Era of Genomic Medicine. In Ginsburg & Willard (Eds.), Genomic and Personalized Medicine (2nd edition, ch 48, pp. 540-558). Elsevier.
  2. Benjamin IJ, Gillespie HS (2012). Infiltrative and Protein Misfolding Myocardial Diseases. In Hill JA, Olson EN (Eds.), Muscle: Fundamental Biology and Mechanisms of Disease (1, 1, pp. 625-638). Elsevier.

Video/Film/CD/Web/Podcast

  1. Benjamin IJ, Weinbaum S, Deemer L (09/2012). Discussion of "Microcalcifications in Vulnerable Plaque Rupture" by Natalia Maldonado Am J Physiol Heart Circ Physiol, published online July 9, 2012 [Podcast]. Bethesda, MD: AJP. Available: http://ajpheart.podbean.com/2012/09/.
  2. Benjamin IJ, Jo H, Holliday C, Miller J (08/2011). Discussion of "Discovery of Shear- and Side-specific miRNAs and mRNAs in Human Aortic Valvular Endothelial Cells" by Casey Holliday, Am J Physiol Heart Circ Physiol., June 24, 2011 [Podcast]. Bethesda, MD: AJP. Available: http://ajpheart.podbean.com/.
  3. Benjamin IJ, Taylor B, Weintraub N (2011). Discussion of 'Catalase overexpression in aortic smooth muscle prevents pathological mechanical changes underlying abdominal aortic aneurysm formation' by Kathryn Maiellaro-Rafferty, Am J Physiol Heart Circ, May 6, 2011 (Ms # H-00040-2011R1) [Podcast]. Bethesda, MD: AJP. Available: http://ajpheart.podbean.com/.