Elena A. Goncharova, PhD
Elena Goncharova, PhD
Associate Professor of Medicine,
Dr. Elena Goncharova received her PhD from the Department of Basic Medicine at the Moscow State University and Cardiology Research Center, Russian Academy of Science, Moscow, Russia, in 2000 and then completed her postdoctoral training at the University of Pennsylvania School of Medicine. In 2009, she was appointed as a Research Assistant Professor at the Allergy and Critical Care Division at the University of Pennsylvania School of Medicine. In July of 2013, Dr. Goncharova joined Division of Pulmonary, Allergy and Critical Care of the University of Pittsburgh School of Medicine and Vascular Medicine Institute as an Associate Professor.
Academic and Research Interests
Dr. Goncharova’s research interests have focused on the signaling mechanisms regulating cellular energy metabolism, proliferation, motility and survival as it relates to the pathogenesis of pulmonary arterial hypertension (PAH) and pulmonary lymphangioleiomyomatosis (LAM). Her current work specifically focuses on the role of mammalian target of rapamycin (mTOR) signaling network in metabolism, proliferation, and survival of pulmonary vascular smooth muscle cells in PAH.
mTOR acts through two functionally distinct complexes, mTORC1 (mTOR-raptor) and mTORC2 (mTOR-rictor). Recently, Dr. Goncharova’s lab has shown that both mTORC1 and mTORC2 signaling pathways are required for proliferation of pulmonary arterial vascular smooth muscle cells under chronic hypoxia, a recognized trigger of pulmonary vascular disease. They also dissected novel signaling mechanism regulating pulmonary vascular smooth muscle cell remodeling in human PAH. Dr. Goncharova identified a critical role for Nox4-mTORC2 signaling in altered energy metabolism, abnormal proliferation and survival of pulmonary vascular smooth muscle cells and demonstrated attractiveness of this pathway as a potential molecular target for therapeutic intervention.
mTORC2-Akt signaling is up-regulated in small remodeled PAs from human PAH lungs (right) compared to non-diseased subjects (left).
Green - SM alpha-actin,
Vessel Radius maps of lung pulmonary vasculature from rat maintained under normoxia (left) and rats with hypoxia-induced pulmonary hypertension treated with vehicle (middle) or mTOR kinase inhibitor (right).
Goncharov DA, Kudryashova TV, Ziai H, Ihida-Stansbury K, Delisser H, Krymskaya VP, Tuder RM, Kawut SM, Goncharova EA. mTORC2 Coordinates Pulmonary Artery Smooth Muscle Cell Metabolism, Proliferation and Survival in Pulmonary Arterial Hypertension. Circulation. 2014, 129(8):864-74
Goncharova EA, Goncharov DA, James ML, Atochina-Vasserman EN, Stepanova V, Hong SB, Li H, Gonzales L, Baba M, Linehan WM, Gow AJ, Margulies S, Guttentag S, Schmidt LS, Krymskaya VP. Folliculin Controls Lung Alveolar Enlargement and Epithelial Cell Survival through E-Cadherin, LKB1, and AMPK. Cell Rep. 2014, 7(2):412-23
Goncharova EA. mTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects. FASEB J. 2013, 27(5):1796-807
Goncharova EA, Goncharov DA, Fehrenbach M, Khavin I, Ducka B, Hino O, Colby TV, Merrilees MJ, Haczku A, Albelda SM, Krymskaya VP. Prevention of alveolar destruction and airspace enlargement in a mouse model of pulmonary lymphangioleiomyomatosis (LAM). Sci Transl Med. 2012 4(154):154ra134.
Goncharova EA, Goncharov DA, Li H, Pimtong W, Lu S, Khavin I, Krymskaya VP. mTORC2 is required for proliferation and survival of TSC2-null cells. Mol Cell Biol. 2011 Jun;31(12):2484-98.
Krymskaya VP, Snow J, Cesarone G, Khavin I, Goncharov DA, Lim PN, Veasey SC, Ihida-Stansbury K, Jones PL, Goncharova EA. mTOR is required for pulmonary arterial vascular smooth muscle cell proliferation under chronic hypoxia. FASEB J. 2011;25(6):1922-33.
Krymskaya VP, Goncharova EA. PI3K/mTORC1 activation in hamartoma syndromes: therapeutic prospects. Cell Cycle. 2009 Feb 1;8(3):403-13.
Goncharova E, Goncharov D, Noonan D, Krymskaya VP. TSC2 modulates actin cytoskeleton and focal adhesion through TSC1-binding domain and the Rac1 GTPase. J Cell Biol. 2004 Dec 20;167(6):1171-82.
Goncharova EA, Goncharov DA, Eszterhas A, Hunter DS, Glassberg MK, Yeung RS, Walker CL, Noonan D, Kwiatkowski DJ, Chou MM, Panettieri RA Jr, Krymskaya VP. Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). J Biol Chem. 2002 Aug 23;277(34):30958-67.
News and Press Releases
Mouse Model of Debilitating Lung Disease Suggests Potential Treatment Regimen