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Vera P. Krymskaya, PhD, MBA, FCPP

Vera P. Krymskaya, PhD, MBA, FCPP Researcher

Professor of Medicine

Languages spoken:

  • English
  • Russian
  • Ukrainian

Dr. Krymskaya is employed by Penn Medicine.

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About Dr. Vera P. Krymskaya

My lab conducts basic and translational research focusing on the role of highly integrated signaling network merging on the PI3K-TSC2-mTOR in rare and common lung diseases. The work for which we receive the most recognition is discovery of the TSC2 function as a negative regulator of the mTOR. My lab was first to establish human LAM cell cultures to demonstrate efficacy of rapamycin for inhibition of  mTORC1 and abrogating LAM cell growth. This key evidence paved the way for clinical trials and to FDA approval of rapamycin for treatment of LAM and TS-LAM. Our discovery that TSC2 deregulates Rho GTPase and LAM cell survival through mTORC2 signaling led to (1) preclinical study of novel combinational therapy using our novel metastatic model of LAM, and (2) phase 2 SOS clinical trial (clinicaltrials.gov, NCT02061397) to determine the safety of combined treatment of simvastatin and sirolimus or everolimus in patients with sporadic LAM and TS-LAM, on which I was the Principal Investigator. In our investigation into immunity in LAM we (1) identified PD-L1 upregulation in LAM lungs, (2) developed novel immunocompetent mouse model of LAM, and (3) performed preclinical study of anti-PD1 antibody to improve animal survival as a proof-of-principal for treatment of LAM.

In addition to developing a comprehensive research program, I am committed to teaching and training of graduate students, postdoctoral and research fellows. My trainees have been awarded extramural funding including R21 and RO1. As a member of Cell Biology, Physiology, and Metabolism graduate group, I also lecture to graduate students, postdocs and fellows at PENN, nationally and internationally. As a Director of Education at the Airway Biology Initiative, I developed unique teaching and learning opportunities for PENN and Drexel University CO-OP students. The Bioethics and Research Conduct Course which I developed is essential for the T32 pulmonary fellowship training program. Since 2011, I also serve as a permanent Chair of the organizing committee for the  Annual Respiration Research Retreat, a unique learning and teaching event for pulmonary researchers, clinicians, fellows and postdocs in the greater Philadelphia region. As a Chair of the Penn Forum for Women Faculty, I work with the Provost office to build a community of women scholars across 12 Schools at the University of Pennsylvania.

Memberships

American Thoracic Society, Respiratory Cell & Molecular Biology Assembly, International Cancer Research Trust New Zealand, International Institute for Regenerative Medicine, University of Pennsylvania Perelman School of Medicine, Local NIH Rare Diseases Clinical Research Network, International Orphan Disease Center, University of Pennsylvania, Local Penn Forum for Women Faculty, Local Scientific Advisory Board, Castleman's Disease Collaborative Network, International The College of Physicians of Philadelphia, National The LAM Foundation, International The Lymphangioleiomyomatosis (LAM) Foundation Scientific Advisory Board, International The National Disease Research Interchange, National Tuberous Sclerosis Complex Research Program, DOD Medical Research, International Tuberous Sclerosis Complex Research Program, International University of California Tobacco-Related Disease Research Program, Cancer-Basic Research Review Panel, National

Hospital Affiliation

Dr. Krymskaya is employed by Penn Medicine.

Research

Description of Research Expertise:

Basic and translational research in rare and common lung diseases: pulmonary lymphangioleiomyomatosis (LAM), tuberous sclerosis (TS), Birt-Hogg-Dube (BHD); Multicentric Castleman Disease (MCD), pulmonary arterial hypertension (PAH), asthma; Cellular signaling networks: phosphatidylinositol 3-kinase (PI3K), Akt, tumor suppressor complex TSC1/TSC2, protein translational regulation, mTOR,LKB1, AMPK, FLCN, RhoA GTPase, Rac1 GTPase, STAT3; Airway smooth muscle cell biology and remodeling,vascular smooth muscle cell biology and remodeling, cell growth, cell proliferation, cell migration, invasiveness; animal models of lung diseases.

Selected Publications:

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 Reports 7 (2): 412-423,2014.

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): 154ra134,2012.

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 (12): 2484-98,2011.

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 129 (8): 864-874,2014.

Elena A. Goncharova, Dmitry A. Goncharov, and Vera P. Krymskaya: Tumor suppressors TSC1 and TSC2 differentially modulate actin cytoskeleton and motility of mouse embryonic fibroblasts The LAM Foundation 17th Annual International Conference : 48,2014.

Atochina-Vasserman EN, Guo CJ, Abramova E, Golden TN, Sims M, James ML, Beers MF, Gow AJ, Krymskaya VP: Surfactant Dysfunction and Lung Inflammation in the Female Mouse Model of Lymphangioleiomyomatosis American Journal of Respiratory Cell and Molecular Biology 53 (1): 96-104,2015.

Goncharova EA, Goncharov DA, Noonan D, Krymskaya VP: TSC2 modulates actin cytoskeleton and cell adhesion through TSC1-binding domain and the Rac1 GTPase Journal of Cell Biology 167 (6): 1171-1182,2004.

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) Journal of Biological Chemistry 277 (34): 30958-67,2002.

Stephen R. Hammes and Vera P. Krymskaya: Targeted Approaches Toward Understanding and Treating Pulmonary Lymphangioleiomyomatosis (LAM) Hormones and Cancer 4 (2): 70-7,2013.

Krymskaya VP: Therapeutic Strategies for Treatment of Pulmonary Lymphangioleiomyomatosis (LAM) Expert Opinion on Orphan Drugs 2 (10): 1063-1074,2014.

View all publications

Academic Contact Info

219 Stemmler Hall
3450 Hamilton Walk

Philadelphia, PA 19104-6118
Phone: (215) 573-9861

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