About me
- Faculty Senate Executive Committee
- Penn Forum for Women Faculty
- Professor of Medicine (Pulmonary, Allergy and Critical Care)
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 the teaching and training of graduate students, postdocs, and research fellows. My trainees have been awarded extramural funding, including R21 and RO1. As a member of the Cell Biology, Physiology, and Metabolism graduate group, I also lecture to graduate students, postdocs, and fellows at Penn, nationally and internationally.
As 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 served for 10 years as 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 Chair of the Penn Forum for Women Faculty, I worked with the Office of the Provost to build a community of women scholars across 12 schools at the University of Pennsylvania.
My Locations
Qualifications and experience
- American Thoracic Society, Respiratory Cell & Molecular Biology Assembly, International
- Institute for Regenerative Medicine, University of Pennsylvania Perelman School of Medicine, Local
- NIH/NHLBI, 2025/10 HLBP (26)2, National
- Orphan Disease Center, University of Pennsylvania, Local
- Penn Forum for Women Faculty, International
- The College of Physicians of Philadelphia, National
- The LAM Foundation, International
- The LAM Foundation, International
- The LAM Foundation, International
- The Lymphangioleiomyomatosis (LAM) Foundation Scientific Advisory Board, International
- The National Disease Research Interchange, National
- The National Disease Research Interchange, National
Treatments and Conditions
My research
Obraztsova K, Basil MC, Rue R, Sivakumar A, Lin SM, Mukhitov AR, Gritsiuta AI, Evans JF, Kopp M, Katzen J, Robichaud A, Atochina-Vasserman EN, Li S, Carl J, Babu A, Morley MP, Cantu E, Beers MF, Frank DB, Morrisey EE, Krymskaya VP mTORC1 activation in lung mesenchyme drives sex- and age-dependent pulmonary structure and function decline , Nature Communications, 11(1): 2020,5640
Evans JF, Obraztsova K, Lin SM, Krymskaya VP CrossTORC and Wntegration in disease: Focus on Lymphangioleiomyomatosis , International Journal of Molecular Sciences, 22(5): 2021,2233-2248
Krymskaya VP, Courtwright AM, Fleck V, Dorgan D, Kotloff R, McCormack FX, Kreider M A phase II clinical trial of the Safety Of Simvastatin (SOS) in patients with pulmonary lymphangioleiomyomatosis and with tuberous sclerosis complex , Respiratory Medicine, 163: 2020,105898
Evans JF, Rue RW, Mukhitov AR, Obraztsova K, Smith CJ, Krymskaya VP Inhibition of growth of TSC2-null cells by a PI3K/mTOR inhibitor but not by a selective MNK1/2 inhibitor , Biomolecules: Molecular Pathology, Molecular Mechanisms of Lung Diseases, 10(1): 2019,28
Kovalenko A, Sanin A, Kosmas K, Zhang L, Wang J, Akl EW, Giannikou K, Probst CK, Hougard TR, Rue RW, Krymskaya VP, Asara JM, Lam HC, Kwiatkowski DJ, Henske EP, Filippakis H Therapeutic targeting of DGKA-mediated macropinocytosis leads to phospholipid reprogramming in Tuberous Sclerosis Complex , Cancer Research, 81(8): 2021,2086-2100
Li H, Oh HB, Viollet B, Schmidt LS, Linehan WM, Krymskaya VP, Hong SB Requirement of FLCN tumor suppressor gene for mTORC1-mediated inhibition of TFE3 transcriptional activity , bioRxiv: 2020
Han F, Dellacecca ER, Barse LW, Cosgrove C, Henning SW, Ankney CM, Jaishankar D, Yemelyanov A, Krymskaya VP, Dilling DF, Le Poole IC Adoptive T cell transfer to treat lymphangioleiomyomatosis , American Journal of Respiratory Cell and Molecular Biology, 62(6): 2020,793-804
Krymskaya VP, McCormack FX Lymphangioleiomyomatosis: a monogenic model of malignancy , Annual Review of Medicine, 68: 2017,69-83