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Description
ABSTRACT
SIRT7 is a longevity regulator and integrator of many cell stress response pathways. SIRT7
expression is decreased with chronological age, as such SIRT7 KO mice are short lived and
mimic many facets of human aging such as hepatic steatosis, cardiac dysfunction, and a
myeloid-skewed hematopoietic system. Here, I aim to demonstrate that mitochondrial quality
control (mitoQC) responses are dysregulated with age due to loss of SIRT7 and that this
contributes to defects in the aged hematopoietic system, such as clonal hematopoiesis. Clonal
hematopoiesis is a pre-leukemic state driven by the outgrowth of hematopoietic stem and
progenitor cell (HSPC) clones and is associated with an increased risk for acute myeloid
leukemia as well as diseases of the periphery like cardiovascular disease due to the actions of
HSPC progeny - tissue infiltrating innate immune cells. Targeting the SIRT7-mitoQC axis in
the aged hematopoietic system will have far reaching effects as the hematopoietic system
touches all tissues through immune surveillance and immune cell’s ability to take up residence
in peripheral tissues.
Status | Active |
---|---|
Effective start/end date | 3/1/17 → 12/31/26 |
Funding
- National Institute of General Medical Sciences
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Projects
- 1 Active
-
University of Kentucky Center for Cancer Metabolism (Admin Core)
Zhou, B. (PI), Brainson, C. (CoI), Chaiswing, L. (CoI), D'Orazio, J. (CoI), Duncan, E. (CoI), Fan, W.-M. (CoI), Fong, K. W. (CoI), Hao, Z. (CoI), Hersh, L. (CoI), Higashi, R. (CoI), Jia, J. (CoI), Lane, A. (CoI), Liu, J. (CoI), Liu, X. (CoI), Moseley, H. (CoI), Myint, Z. (CoI), Rellinger, E. (CoI), Thorson, J. (CoI), Van Eldik, L. (CoI), Vanderford, N. (CoI), Wang, C. (CoI), Weiss, H. (CoI) & Yalniz, F. (CoI)
National Institute of General Medical Sciences
3/1/17 → 12/31/26
Project: Research project