George E. Taffet, M.D.
Associate Professor of Medicine - Geriatrics
Chief, Section of Geriatrics
Education and Training
B.A.: Brown University, Rhode Island
M.D.: Brown University, Rhode Island
Clinical Fellowship: Geriatric Medicine, Baylor College of Medicine, Houston, TX
Research Fellowship: Cardiovascular Sciences, Baylor College of Medicine, Houston, TX
Basic Research Interests
Heart Failure: Calcium and Aging
Dr. Taffet is interested in a type of congestive heart failure (CHF) where the heart contracts well but relaxes poorly. This type of heart failure is found in 50 percent of elderly people with CHF and does not respond to the usual CHF treatment. It is so common in old people because aging itself impairs the relaxation of the heart. Cardiac relaxation is a complicated process that relies on the sarcoplasmic reticulum CaATPase, a pump protein, to remove calcium ions from contractile proteins and sequester them in the sarcoplasmic reticulum. The protein content of the CaATPase is decreased in the senescent Fischer 344 rat, our model for aging.
Along with Dr. Charlotte Tate, our research has shown that endurance exercise will improve cardiac relaxation, increase protein content of the CaATPase, and increase calcium uptake by the sarcoplasmic reticulum. Because exercise is not feasible for everyone, we have embarked on an alternative approach to increasing the CaATPase function by altering the resistance of the sarcoplasmic reticulum membrane to protein movement. Modification of the lipid composition of the sarcoplasmic reticulum membrane results in enhanced CaATPase function.
Dr. Taffet's research focuses on the mechanisms of the modification of pump function associated with alterations in the membrane composition. We will continue to utilize the aging rat and mouse, but will use in vitro and in vivo experiments when long-term experiments are required. Though Dr. Taffet's experience is primarily with the biochemistry and physiology of this system, it is ripe for molecular manipulation to be started within the foreseeable future. However, we will relate all such manipulations back to physiological measurements in the mouse or the rat.
- Hartley CJ, Reddy AK, Madala S, Michael LH, Entman ML and Taffet GE. (2007). Effects of isoflurane on coronary blood flow velocity in young, old and ApoE(-/-) mice measured by Doppler ultrasound. Ultrasound Med Biol 33:512-21.
- Setyadi HG, Cohen PR, Schulze KE, Mason SH, Martinelli PT, Alford EL, Taffet GE and Nelson BR. (2007). Trigeminal trophic syndrome. South Med J 100:43-8.
- Xie M, Zhang D, Dyck JR, Li Y, Zhang H, Morishima M, Mann DL, Taffet GE, Baldini A, Khoury DS and Schneider MD. (2006). Free in PMC: a pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway. Proc Natl Acad Sci USA 103:17378-83.
- Kannankeril PJ, Mitchell BM, Goonasekera SA, Chelu MG, Zhang W, Sood S, Kearney DL, Danila CI, De Biasi M, Wehrens XH, Pautler RG, Roden DM, Taffet GE, Dirksen RT, Anderson ME and Hamilton SL. (2006). Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy. Proc Natl Acad Sci USA 103:12179-84.
- Zhang YM, Bo J, Taffet GE, Chang J, Shi J, Reddy AK, Michael LH, Schneider MD, Entman ML, Schwartz RJ and Wei L. (2006). Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis. FASEB J 20:916-25.
- Reddy AK, Taffet GE, Prchal JF, Michael LH, Entman ML and Hartley CJ. (2004). Effect of cellular elements on pressure-velocity relationship in mice. Conf Proc IEEE Eng Med Biol Soc 5:3720-2.
- Hartley CJ, Reddy AK, Madala S, Entman ML, Michael LH and Taffet GE. (2004). Noninvasive ultrasonic measurement of arterial wall motion in mice. Conf Proc IEEE Eng Med Biol Soc 5:3688-91.