Penn Cardiovascular Institute

Penn Cardiovascular Institute Research Directory

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Description of CVI Expertise

CVI Program Unit(s):
Myocyte Biology / Heart Failure
Pulmonary Vascular Disease

CVI Research Description:
My laboratory is investigating signaling mechanisms of smooth muscle cell proliferation and migration as it relates to:
1) the pathobiology of lymphangioleiomyomatosis (LAM);
2) pulmonary arterial hypertension (PAH); and
3) asthma.

Recently, we had made a key contribution to the understanding of the molecular mechanisms regulating abnormal smooth muscle cell proliferation and migration in LAM. We identified the role of tumor suppressor TSC2 as a negative regulator of S6K1, and S6K1 as a molecular target to treat LAM disease. Our studies also identified rapamycin as a promising therapeutic strategy for LAM patients, and a Phase 1-2 clinical trail of rapamycin is currently being conducted at the Children's Hospital Medical Center in Cincinnati. Current project which is oriented to fellow participation and related to cardiovascular research include bench (basic, signal transduction) project, which goal is to determine a role of PI3K-TSC1/TSC2-mTOR-S6K1 signaling pathway in regulating pulmonary arterial vascular smooth muscle cell growth and proliferation.

Selected Publications

Elena A. Goncharova, Dmitry A. Goncharov, Melane Fehrenbach, Irene Khavin, Blerina Ducka, Okio Hino, Thomas V. Colby, Mervyn J. Merrilees, Angela Haczku, Steven M. Albelda, and Vera P. Krymskaya: Prevention of Alveolar Destruction and Airspace Enlargement in a Mouse Model of Pulmonary Lymphangioleiomyomatosis (LAM). Science Translational Medicine 4(154): 154ra134, October 2012 Notes: cited by F1000Prime.

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 Molecular and Cellular Biology 31: 2484-2498, March 2011.

Lyn Moir, Judith Black, and Vera P. Krymskaya: TSC2 modulates cell adhesion and migration via integrin α1β1. American Journal of Physiology - Lung Cellular and Molecular Physiology 303: L703-L710, October 2012.

Elena A Goncharova, Irene S Khavin, Dmitry A Goncharov and Vera P Krymskaya: Differential Effects of Formoterol on Thrombin- and PDGF-Induced Proliferation of Human Pulmonary Arterial Vascular Smooth Muscle Cells Respiratory Research 1186/1465-9921-13-109, Nov 27 2012.

Moir LM, Hy Ng, Poniris MH, Santa T, Burgess JK, Oliver BGG, Krymskaya VP, Black JL: Doxycycline inhibits matrix metalloproteinase-2 secretion from TSC2-null mouse embryonic fibroblasts and lymphangioleiomyomatosis (LAM) cells. British Journal of Pharmacology 164(1): 83-92, Sept 2011.

Gautam Damera, Kirk M. Druey, Philip R. Cooper, Vera P. Krymskaya, Roy J. Soberman, Yassine Amrani, Toshinori Hoshi, Christopher E. Brightling, Reynold A. Panettieri, Jr.: An RGS4-Mediated Phenotypic Switch of Bronchial Smooth Muscle Cells Promotes Fixed Airway Obstruction in Asthma. PLoS One 7(1): e28504, January 2012.

Vera P Krymskaya, Jennifer Snow, Gregory Cesarone, Irene Khavin, Dmitry Goncharov, Poay Lim, Sigrid Veasey, Kaori Ihida-Stanbury, Peter Jones, Elena Goncharova: mTOR is Required for Pulmonary Arterial Vascular Smooth Muscle Cell Proliferation Under Chronic Hypoxia The FASEB Journal 25(6): 1922-1933, June 2011.

Doug A. Medvetz, Damir Khabibullin, Venkatesh Hariharan, Pat P. Ongusaha, Elena A. Goncharova, Tanja Schlechter,Thomas N. Darling, Ilse Hofmann, Vera P. Krymskaya, James K. Liao, Hayden Huang, Elizabeth P. Henske: Folliculin, the product of the Birt-Hogg-Dube tumor suppressor gene, interacts with the adherens junction protein p0071 to regulate cell-cell adhesion. PLoS One 7(11): e47842, November 2012.

Koziol-White C., Goncharova E., Cao G., Johnson, M., Krymskaya V. P., Panettieri R.A.: DHEA-S inhibits human neutrophil and airway smooth muscle migration. BBA - Molecular Basis of Disease 1822: 1638-1642, October 2012.

Elena A. Goncharova, Dmitry A. Goncharov, Hengjiang Zhao, Raymond Penn, Richard Knowles, Vera P. Krymskaya, and Reynold A. Panettieri, Jr.: β2-Adrenergic Receptor Agonists Modulate Human Airway Smooth Muscle Cell Migration Via Vasodilator Stimulated Phophoprotein. Amer J Respir Cell Mol Biol 46(1): 48-54, January 2012.

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Last updated: 08/17/2015
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