Contact Information:
Aging & Metabolism Research Program, MS 21
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-3116
Fax: (405) 271-1437
ann-chiao@omrf.org
Education:
Postdoc, University of Washington, Seattle, WA, 2011-2017
Ph.D., University of Texas Health Science Center, San Antonio, TX, 2011
M.Phil., Chinese University of Hong Kong, Molecular Biotechnology, 2006
B.Sc., Chinese University of Hong Kong, 2002
Research Interests:
Aging exponentially increases the risk of cardiovascular disease and impairs baseline cardiac function, especially diastolic function. Diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are both increasing in prevalence in the aged population, contribute to exercise intolerance in the elderly, and are presently without effective treatment. While phenotypes of cardiac aging are well-characterized, the molecular mechanisms of cardiac aging have not been well-established.
My research program focuses on dissecting the molecular mechanisms of cardiac aging and age-related diastolic dysfunction, and developing potential interventions to treat cardiac aging and HFpEF. We use in vivo and in vitro approaches to study the physiological, biochemical and proteomic changes of cardiac aging in mouse models.
We and other have demonstrated that late-life inhibition of mTOR signaling, by caloric restriction (CR) or rapamycin, can reverse cardiac aging phenotypes in mice. Rapamycin treatment inhibits mTOR signaling and induces proteomic and metabolic remodeling in aged hearts. However, how these proteomic and metabolic changes mediate improved diastolic function remain to be established. The research in my laboratory aims to determine the molecular mechanisms of rapamycin-induced reversal of diastolic dysfunction in aged hearts. Specifically, our studies focus on 1) how rapamycin regulates cardiomyocyte relaxation properties in the aging hearts and 2) how rapamycin remodels cardiac extracellular matrix to modify passive myocardial stiffness. In addition, we hope to define the signaling pathways by which rapamycin mediates changes in these key determinants of diastolic function.
The overall goals of the laboratory are to identify novel regulators of cardiac aging and diastolic dysfunction, and to apply this knowledge to the development of therapeutics for cardiac aging and HFpEF.
Selected Publications:
-Varshney R, Ranjit R, Chiao YA, Kinter M, Ahn B. Myocardial Hypertrophy and Compensatory Increase in Systolic Function in a Mouse Model of Oxidative Stress. Int J Mol Sci 22, 2021 February, PMID: 33670798, PMCID: PMC7921997
-Chiao YA, Zhang H, Sweetwyne M, Whitson J, Ting YS, Basisty N, Pino LK, Quarles E, Nguyen NH, Campbell MD, Zhang T, Gaffrey MJ, Merrihew G, Wang L, Yue Y, Duan D, Granzier HL, Szeto HH, Qian WJ, Marcinek D, MacCoss MJ, Rabinovitch P. Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. Elife 9, 2020 July, PMID: 32648542, PMCID: PMC7377906
-Quarles E, Basisty N, Chiao YA, Merrihew G, Gu H, Sweetwyne MT, Fredrickson J, Nguyen NH, Razumova M, Kooiker K, Moussavi-Harami F, Regnier M, Quarles C, MacCoss M, Rabinovitch PS. Rapamycin persistently improves cardiac function in aged, male and female mice, even following cessation of treatment. Aging Cell 19:e13086, 2020 February, PMID: 31823466, PMCID: PMC6996961
Selected Publications
-Chiao YA,* Zhang H, Sweetwyne M, Whitson J, Ting YS, Basisty N, Pino L, Quarles E, Thi Nguyen N-H, Campbell MD, Zhang T, Gaffrey MJ, Merrihew G, Wang L, Yue Y, Duan D, Granzier H, Szeto HH, Qian W-J, Marcinek D, MacCoss MJ and Rabinovitch PS.* Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. Elife. 2020 Jul 10;9:e55513. (*corresponding authors) PMID: 32648542 PMCID: PMC7377906
-Chiao YA, Kolwicz SC, Basisty N, Gagnidze A, Zhang J, Gu H, Djukovic D, Beyer RP, Raftery D, MacCoss MJ, Tian R, Rabinovitch PS. Rapamycin transiently induces mitochondrial remodeling to reprogram energy metabolism in old hearts. Aging (Albany NY). 2016 Feb;8(2):314-27. PMID: 26872208 PMCID: PMC4789585
-Chiao YA and Rabinovitch PS. The Aging Heart. Cold Spring Harb Perspect Med. 2015 Sep 1;5(9):a025148.
-Karunadharma PP*, Basisty N*, Chiao YA*, Dai D-F, Drake R, Levy N, Koh WJ, Emond MJ, Kruse S, Marcinek D, MacCoss MJ, Rabinovitch PS. Respiratory chain protein turnover rates in mice are highly heterogeneous but strikingly conserved across tissues, ages and treatments. FASEB J. 2015 Aug;29(8):3582-92. *Authors have equal contributions. PMID: 25977255 PMCID: PMC4511201
-Dai D-F*, Karunadharma PP*, Chiao YA*, Basisty N*, Crispin D, Hsieh EJ, Chen T, Gu H, Djukovic D, Raftery D, Beyer RP, MacCoss MJ, Rabinovitch PS. Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart. Aging Cell. 2014 Jun;13(3):529-39. *Authors have equal contributions PMID: 24612461 PMCID: PMC4040127
-Chiao YA, Jin Y, Zamilpa R, Dai Q, Ramirez TA, Zhang J, and Lindsey ML. Matrix Metalloproteinase-9 Deletion Attenuates Myocardial Fibrosis and Diastolic Dysfunction in Ageing Mice. Cardiovasc Res. 2012 Dec 1;96(3):444-55. PMID: 22918978 PMCID: PMC3500048
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