Peter Rabinovitch

Phone: (206) 685-3761
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The focus of Dr. Rabinovitch's laboratory research is on the use of genetically altered mouse models to examine the effects of cell signaling and reactive oxygen species (ROS) on lifespan and healthspan. Transgenic mice that overexpress catalase have been found to be protected against multiple health challenges, including cardiac aging, sarcopenia and some cancers. Similar benefits are conferred by treating mice with the SS-31 tetrapeptide. The interrelationships of mitochondrial ROS and mitochondrial damage with cell signaling pathways that mediate improved healthspan, including resistance to cardiac hypertrophy and failure, are thus of central interest to the laboratory. As the mTOR pathway is a strong candidate in this linkage, we are using transgenic mice with altered mTOR signaling to explore this relationship. In addition to physiological and biochemical assays, proteomic and genomic technologies are being actively utilized in laboratory studies.

Dr. Rabinovitch is the founding director (1985) of the University of Washington Nathan Shock Center for Excellence in the Basic Biology of Aging, one of 5 such NIA funded Centers in the country. He has been the Director of a T32 Biology of Aging Training Grant at the University of Washington since 1997. He is current Chairman of the NIA-B Study Section (NIH Biological Aging Review Committee). He has been funded continuously by the NIA since 1981, including as the PI of a Program Project in aging since 2004. He is a current recipient of an Ellison Medical Foundation Senior Scholar in Aging grant award, and a Breakthroughs in Gerontology grant award from the American Federation for Aging Research.

Selected Relevant Publications:
  1. Risques RR, Lai LA, Brentnall TA, Li L, Feng Z, Gallaher J, Mandelson MT, Potter JD, Bronner MP, Rabinovitch PS. Ulcerative Colitis is a Disease Of Accelerated Colon Aging: Evidence From Telomere Attrition And Increased DNA Damage. Gastroenterology 135:410-8, 2008. PMID: 18519043.
  2. Treuting PM, Linford NJ, Knoblaugh SE, Emond MJ, Morton JF, Martin GM, Rabinovitch PS, Ladiges WC. Reduction of Age-associated Pathology in Old Mice by Overexpression of Catalase in Mitochondria. Journal of Gerontology: Biological Sciences 63:813-22, 2008. PMID: 18772469.
  3. Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW 3rd, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J. Clinical Invest. 2009 Feb 2. pii: 37048. doi: 10.1172/JCI37048. PMID: 19188683
  4. Dai, D-F, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ, Gollahon K, Martin GM, Loeb LA, Ladiges, Ladiges WC, Rabinovitch PS. Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation 2009 Jun 2;119(21):2789-97. PMID: 19451351
  5. Li D, Lai Y, Yue Y, Rabinovitch PS, Hakim C, Duan D. Ectopic catalase expression in mitochondria by adeno-associated virus enhances exercise performance in mice. PLoS One. 2009 Aug 19;4(8):e6673.PMID: 19690612
  6. Someya S, Xu J, Kondo K, Ding D, Salvi RJ, Yamasoba T, Rabinovitch PS, Weindruch R, Leeuwenburgh C, Tanokura M, Prolla TA. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. PNAS, in press
  7. Dai D-F, Rabinovitch PS, Cardiac Aging in Mice and Humans: the Role of Mitochondrial Oxidative Stress, Trends in Cardiovascular Medicine. 2009,19:213-20. PMID: 20382344
  8. Dai DF, Chen T, Wanagat J, Laflamme M, Marcinek DJ, Emond MJ, Ngo CP, Prolla TA, Rabinovitch PS. Age-Dependent Cardiomyopathy in Mitochondrial Mutator Mice is Attenuated by Overexpression of Catalase Targeted to Mitochondria. Aging Cell. 2010; 9:536-44 PMID: 20456298
  9. Wanagat J, Dai DF, Rabinovitch P. Mitochondrial oxidative stress and mammalian healthspan. Mech Ageing Dev. 2010 Jun 8. [Epub ahead of print]. PMID: 20566356
  10. Lee HY, Choi CS, Birkenfeld AL, Alves TC, Jornayvaz FR, Jurczak MJ, Zhang D, Woo DK, Shadel GS, Ladiges W, Rabinovitch PS, Santos JH, Petersen KF, Samuel VT, Shulman GI Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance. Cell Metab. 2010 Dec 1;12(6):668-74. PMCID: PMC3013349
  11. Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-Cintrón M, Chen T, Marcinek DJ, Dorn GW 2nd, Kang YJ, Prolla TA, Santana LF, Rabinovitch PS Mitochondrial Oxidative Stress Mediates Angiotensin II-Induced Cardiac Hypertrophy and G{alpha}q Overexpression-Induced Heart Failure. Circ Res. 2011, 108(7):837-46. PMID: 21311045
  12. Dai DF, Rabinovitch P. Mitochondrial oxidative stress mediates induction of autophagy and hypertrophy in angiotensin-II treated mouse hearts. Autophagy. 2011 Aug 1;7(8). [Epub ahead of print] PMID: 21505274
  13. Dai D-F, Chen T, Szeto H, Nieves-Cintrón M, Summer V, Santana LF, Rabinovitch PS. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J. American Coll. Cardiol., 2011 Jun 28;58(1):73-82 PMID 21620606.
  14. Dai DF, Hsieh EJ, Liu Y, Chen T, Beyer RP, Chin MT, Maccoss MJ, Rabinovitch PS. Mitochondrial proteome remodeling in pressure overload-induced heart failure: the role of mitochondrial oxidative stress. Cardiovasc Res. 2012 Jan 1;93(1):79-88. Epub 2011 Oct 19. PubMed PMID: 22012956; PMCID: PMC3243039.
  15. Dai DF, Chen T, Johnson S, Szeto HH, Rabinovitch PS. Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease. Antioxid Redox Signal. 2012 Jan 9. [Epub ahead of print] PubMed PMID: 22229339.
  16. Johnson S, Rabinovitch, P. Ex-vivo imaging of excised tissue using vital dyes and confocal microscopy. Current Protocols in Cytometry, in press.