Richard Kitsis, MD

 

Professor, Departments of Cell Biology and Medicine Forchheimer Bldg., Room G46 718 430-2609 kitsis@aecom.yu.edu Complete list of publications

Research interests Cell Death: Fundamental Mechanisms and Roles in Human Disease The most basic decision that any cell can make is to grow (proliferate or hypertrophy), differentiate, or die. Our laboratory is interested in the connections among these processes. A major focus is the fundamental mechanisms that mediate cell death and the role that cell death itself plays in major human diseases such as heart disease, cancer, and diabetes. We employ a variety of approaches including molecular and cellular biology, biochemistry, mouse and human genetics, and physiology. Key discoveries from the lab include: 1) Recognition that death-fold domains, an ancient motif found in many apoptotic signaling molecules, engage in non-homotypic, as well as homotypic, interactions. 2) Elucidation of molecular mechanisms by which ARC, an endogenous inhibitor of apoptosis, directly suppresses both extrinsic (death receptor) and intrinsic (mitochondrial/ER) central apoptosis pathways as well as inactivates p53. 3) Observation that ARC is induced in a wide variety of primary human epithelial cancers and plays a causal role in carcinogenesis as well as in chemo- and radiation-resistance. 4) Initial proof of concept that apoptosis plays a critical role in both myocardial infarction (“heart attack”) and heart failure, the major killers in developed societies, and thus may provide a novel therapeutic target in these disorders. The ability of ARC to antagonize both central apoptosis pathways is unique and suggests that it plays an important role in regulating cell death. Accordingly, we are investigating the molecular mechanisms and physiological roles of ARC in a variety of disease processes. In addition, we are asking a number of more general questions about cell death and the relationship of cell death with other fundamental cellular processes. Current areas of investigation include:   Structural basis of ARC’s non-homotypic interactions Mechanisms by which ARC coordinates cell death/survival and death/proliferation Cell death and ARC in the pathogenesis of myocardial infarction and heart failure Cell death and ARC in the pathogenesis of breast cancer. Cell death and ARC in the pathogenesis of diabetes Approaches to manipulate ARC abundance to therapeutic advantage in heart disease and cancer Molecular basis of necrosis.

Recent publications (selected) Nam Y-J, Mani K, Wu L, Peng C-F, Calvert JW, Foo RS-Y, Krishnamurthy B, Miao W, Ashton AW, Lefer DJ, Kitsis RN. The apoptosis inhibitor ARC undergoes ubiquitin-proteasomal-mediated degradation in response to death stimuli: identification of a degradation-resistant mutant. J Biol Chem, 2007. 282: 5522-5528. Kitsis RN, Peng C-F, Cuervo AM. Eat your heart out. Nature Med, 2007. 13: 539-541. Foo RS, Nam YJ, Ostreicher MJ, Metzl MD, Whelan RS, Peng CF, Ashton AW, Fu W, Mani K, Chin SF, Provenzano E, Ellis I, Figg N, Pinder S, Bennett MR, Caldas C, Kitsis RN. Regulation of p53 tetramerization and nuclear export by ARC. Proc Natl Acad Sci U S A, 2007. 104: 20826-20831. Kitsis RN, Jialal I. Inhibiting CRP to limit myocardial damage during acute myocardial infarction? New Eng J Med, 2006. 355: 513-515. Foo RS-Y, Mani K, Kitsis RN. Death begets failure in the heart. J Clin Invest, 2005. 115: 565-571. Mercier I, Vuolo M, Madan R, Xue X, Levalley AJ, Ashton AW, Jasmin J-F, Czaja MT, Lin EY, Armstrong RC, Pollard JW, Kitsis, RN. ARC, an apoptosis suppressor limited to terminally differentiated cells, is induced in human breast cancer and confers chemo- and radiation-resistance. Cell Death Differ, 2005.12:682-686. Pajvani UB, Trujillo ME, Combs TP, Iyengar P, Jelicks L, Roth KA, Kitsis RN, Scherer PE. Fat apoptosis through targeted activation of caspase 8: a new mouse model of inducible and reversible lipoatrophy. Nature Med, 2005. 11: 797-803. Nam Y-J, Mani K, Ashton AW, Peng C-F, Krishnamurthy B, Hayakawa Y, Lee P, Korsmeyer SJ, Kitsis RN. Inhibition of both the extrinsic and intrinsic death pathways through non-homotypic death-fold interactions. Molecular Cell, 2004. 15: 901-912. Wencker D, Chandra M, Nguyen KT, Miao W, Garantziotis S, Factor SM, Shirani J, Armstrong RC, Kitsis RN. A mechanistic role for cardiac myocyte apoptosis in heart failure J Clin Invest, 2003. 111: 1497-1504.

Richard Kitsis: Research interests Faculty research at a glance Birshtein | Bouhassira | Edelmann | Fyodorov | Keogh | Kielian | Kitsis | Nathenson | Query Scharff | Schildkraut | Shafritz | Singer | Skoultchi | Stanley | Steidl |Warner | Ye   Home