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 focuses on investigating pathogenesis and development of alternative therapies for effective treatment of heart and lung diseases, with the particular emphasis of metabolic syndrome, pulmonary hypertension (high blood pressure in the lung; PH), and heart failure with preserved ejection fraction (PH-HFpEF). It is a major complication linked to adverse outcomes with no approved therapies at present. Currently, much of Dr. Lai’s effort is focused on understanding how skeletal muscle defects affect pulmonary vascular (lung vessels) health in PH-HFpEF with a particular focus on myokines (proteins and peptides that can be secreted from skeletal muscle into circulation and can potentially be used as biomarkes for diagnosis and/or prognosis of the disease) and their targets in the pulmonary vasculature. Dr. Lai’s has made several important contributions to the field of pulmonary hypertension research, which include 1) developing mouse and rat models of PH-HFpEF; 2) evaluating the effects and mechanisms of nitrite, metformin, treprostinil, and empagliflozin in PH-HFpEF; 3) identifying candidate biomarkers and proteins associated with metabolic syndrome-induced PH-HFpEF; and 4) assessing the role of endothelial iron-sulfur (Fe-S) cluster deficiency across Group 1-3 PH. The use of inhaled nitrite has led to positive clinical results in patients with PH-HFpEF and has now advanced to a phase 2A clinical trial. Findings from Dr. Lai and collaborators have also led to an ongoing clinical trial assessing the effect of metformin in patients with PH-HFpEF.

Key Publications

Jheng JJ, DesJardin JT, Chen YY, Huot JR, Bai Y, Cook T, Hibbard LM, Rupp JM, Fisher A, Zhang Y, Duarte JD, Desai AA, Machado RF, Simon MA, Lai YC. Plasma Proteomics Identifies B2M as a Regulator of Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction. Arterioscler Thromb Vasc Biol. 2024 Jul; 44(7): 1570-1583. PMID: 38813697. 

Jheng JJ, Bai Y, Noda K, Huot JR, Cook T, Fisher A, Chen YY, Goncharov DA, Goncharova EA, Simon MA, Zhang Y, Forman DE, Rojas M, Machado RF, Auwerx J, Gladwin MT, Lai YC. Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure with Preserved Ejection Fraction. Circulation. 2024 Sep 10; 150: 867-883 doi: 10.1161/CIRCULATIONAHA.124.068624. PMID: 38804138. 

Tang H, Gupta A, Morrisoroe S, Bao C, Schwantes-An TH, Gupta G, Liang S, Sun Y, Chu A, Luo A, Elangovan VR, Sangam S, Shi Y, Naidu S, Jheng JJ, Halliday G, Ciftci-Yilmaz S, Warfel N, Hecker L, Mitra S, Coleman A, Lutz K, Pauciulo M, Lai YC, Javaheri A, Wu WH, Flaherty D, Karnes J, Breuils-Bonnet S, Boucherat O, Bonnet S, Yuan J, Jacobson J, Nichols W, Garcia J, Desai AA. Deficiency of the deubiquitinase, UCHL1, attenuates pulmonary hypertension. Circulation. 2024 May 2. doi: 10.1161/CIRCULATIONAHA.123.065304. (Epub ahead of print). PMID: 38695173. 

Satoh T, Wang L, Espinosa-Diez C, Wang B, Hahn SA, Noda K, Rochon ER, Dent MR, Levine AR, Baust JJ, Wyman S, Wu YL, Triantafyllou GA, Tang Y, Reynolds M, Shiva S, Hilaire CS, Gomez D, Goncharov DA, Goncharova EA, Chan SY, Straub AC, Lai YC, McTiernan CF, Gladwin MT. Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction. Circulation 2021 Aug 24;144(8):615-637. PMID: 34157861. 

Culley MK, Zhao J, Tai YY, Tang Y, Perk D, Negi V, Yu Q, Woodcock CC, Handen A, Speyer G, Kim S, Lai YC, Satoh T, Watson AM, Aaraj YA, Sembrat J, Rojas M, Goncharov D, Goncharova EA, Khan OF, Anderson DG, Dahlman JE, Gurkar AU, Lafyatis R, Fayyaz AU, Redfield MM, Gladwin MT, Rabinovitch M, Gu M, Bertero T, Chan SY. Frataxin deficiency promotes endothelial senescence in pulmonary hypertension. J Clin Invest. 2021 Jun 1;131(11). PMID: 33905372.

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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