42729-Lai, Yen-Chun (Charly)

Yen-Chun (Charly) Lai, PhD

Assistant Professor of Medicine

Assistant Professor of Medicine

Adjunct Assistant Professor of Cellular &amp

Integrative Physiology

Address
R3 C400
PULM
Indianapolis, IN 46202
PubMed:

Bio

Dr. Lai’s research has been focused primarily on investigating pathogenesis and development of alternative therapies for effective treatment of cardiopulmonary diseases, with the particular emphasis of metabolic syndrome, pulmonary hypertension, and heart failure with preserved ejection fraction (PH-HFpEF). She has made several important contributions to the field of pulmonary hypertension research, which include publishing research articles on 1) the effects and mechanisms of nitrite and metformin in a newly developed rat model of PH-HFpEF; 2) establishing mouse model of PH-HFpEF; 3) developing tools for rapid and accurate measurement of pulmonary vascular remodeling; and 4) identifying candidate genes associated with high-fat diet-induced pulmonary hypertension with a genome-wide association study.

 

Currently, much of her effort is focused on unraveling the role of sirtuin-3 (SIRT3) in skeletal muscle and its modulation of endocrine signaling pathways in PH-HFpEF. In a recent work related to an ongoing collaboration with investigators at University of Pittsburgh, she observed an interesting link between skeletal muscle SIRT3 deficiency and remote pulmonary vascular remodeling. This is largely an unexplored area which may provide new mechanistic understanding of PH-HFpEF and potentially answer some key questions related to the treatment of cardiopulmonary diseases, as well as aging. Together with a team of collaborators, she is currently seeking to explore the nature of molecular regulation with respect to skeletal muscle SIRT3 deficiency and remote pulmonary vascular remodeling with a particular focus on lysyl oxidase homolog 2 (LOXL2) and gremlin-1 (Grem1).

 

Additionally, Dr. Lai studies effect of Remodulin (with Dr. Mark Gladwin; University of Pittsburgh), effect of Rapamycin (with Dr. Elena Goncharova; University of Pittsburgh), exercise effects (with Dr. Tim Lahm; Indiana University School of Medicine), and the role of NAMPT (with Dr. Roberto Machado; Indiana University School of Medicine) in PH-HFpEF. As there are no effective therapies for PH-HFpEF treatment available at present, these studies will provide new insight into the development of more specific and effective treatments.

Key Publications

Lai, YC, Tabima DM, Dube JJ, Hughan KS, Goncharov DA, St Croix CM, Garcia-Ocaña A, Goncharova EA, Tofovic SP, Mora AL, Gladwin MT. SIRT3-AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction. Circulation 2016 Feb 23; 133(8): 717-31. PMCID: PMC4766041.

Meng Q, Lai YC, Kelly NJ, Bueno M, Baust JJ, Bachman TN, Goncharova D, Vanderpool RR, Radder JE, Hu J, Goncharova E, Morris AM, Mora AL, Shapiro SD, Gladwin MT. Development of a Mouse Model of Metabolic Syndrome, Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction. American Journal of Respiratory Cell and Molecular Biology 2017 Apr; 56(4):497-505. PMCID: PMC5449511.

Dmitry A. Goncharov, Elena A. Goncharova, Stevan P. Tofovic, Jian Hu, Jeff J. Baust, Andressa Z. Pena, Arnab Ray, Analise Rode, Rebecca R. Vanderpool, Ana L. Mora, Mark T. Gladwin, Yen-Chun Lai. (2018) Metformin Therapy for Pulmonary Hypertension associated with HFpEF versus PAH. American Journal of Respiratory Critical Care Medicine 2018 Sep 1; 198(5): 681-684. PMCID: PMC6118018.

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