Dr. Z. Dave Sharp's lab explores novel strategies to prevent diseases while
mitigating morbidities associated with aging, thereby reducing suffering and
looming economic burden.
They study how chronic mTOR inhibition
prevents, delays, and/or reduces the severity of cancer while mitigating other
negative effects of aging.
Their experiments show this
is possible with a novel enteric formulation of rapamycin, eRapa. Their current
research goals aim to understand the mechanism of action of eRapa in the
prevention of colon cancer using mouse models combined with genetic, epigenetic
and protein synthesis profiling technologies.
Hasty P, Livi CB, Dodds SG, Jones D, Strong R, Javors M, Fischer KE,
Sloane L, Murthy K, Hubbard G, Sun L, Hurez V, Curiel TJ, Sharp ZD. eRapa restores a normal life span in a FAP mouse model. Cancer Prev Res (Phila). 2014 Jan;7(1):169-78.
Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors
MA, Li X, Nadon NL, Nelson JF, Pletcher S, Salmon AB, Sharp ZD, Van
Roekel S, Winkleman L, Strong R. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell. 2013 Dec 17. doi: 10.1111/acel.12194.
Note: The below three
papers tested my proposal to the NIA-ITP that chronic rapamycin treatment mitigates
aging and age-related diseases thereby extending maximum longevity.
Livi CB, Hardman RL, Christy BA, Dodds SG, Jones D, Williams C, Strong
R, Bokov A, Javors MA, Ikeno Y, Hubbard G, Hasty P, Sharp ZD. Rapamycin extends life span of Rb1+/- mice by inhibiting neuroendocrine tumors. Aging (Albany NY). 2013 Feb;5(2):100-10.
Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez
E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD,
Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, Strong R. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci. 2011 Feb;66(2):191-201.
DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL,
Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E,
Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009 Jul 16;460(7253):392-5.