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Description of Research Expertise
Dr. Krymskaya 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 she receives the most recognition is discovery of the TSC2 function as a negative regulator of the mTOR. Her laboratory of Rare Lung Diseases was the first to establish human LAM cell cultures to perform preclinical testing and to demonstrate efficacy of rapamycin for inhibition of mTOR and abrogating LAM cell growth. This key evidence paved the way for two successful clinical trials and to FDA approval in 2015 of rapamycin analogs for treatment of LAM and TS-LAM. The discovery that TSC2 deregulates Rho GTPase and LAM cell survival through mTORC2 signaling and development of novel mouse model of LAM, led to preclinical study of novel combinational therapy for LAM, and 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 Dr. Krymskaya was the Principal Investigator. Investigation into immunity in LAM, led to identification of PD-L1 upregulation in LAM lungs, developing a novel immunocompetent mouse model of LAM, and performance of preclinical study of anti-PD1 antibody to improve animal survival as a proof-of-principal for treatment of LAM. The recent study of LAM lung cell composition and novel LAM-relevant genetic animal model lay the groundwork for developing a novel mechanistic understanding of LAM pathobiology involving mTORC1-WNT signaling crosstalk and provide essential steps towards expending the repertoire of effective therapies for this devastating disease.
Description of Research Expertise
Dr. Krymskaya 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 she receives the most recognition is discovery of the TSC2 function as a negative regulator of the mTOR. Her laboratory of Rare Lung Diseases was the first to establish human LAM cell cultures to perform preclinical testing and to demonstrate efficacy of rapamycin for inhibition of mTOR and abrogating LAM cell growth. This key evidence paved the way for two successful clinical trials and to FDA approval in 2015 of rapamycin analogs for treatment of LAM and TS-LAM. The discovery that TSC2 deregulates Rho GTPase and LAM cell survival through mTORC2 signaling and development of novel mouse model of LAM, led to preclinical study of novel combinational therapy for LAM, and 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 Dr. Krymskaya was the Principal Investigator. Investigation into immunity in LAM, led to identification of PD-L1 upregulation in LAM lungs, developing a novel immunocompetent mouse model of LAM, and performance of preclinical study of anti-PD1 antibody to improve animal survival as a proof-of-principal for treatment of LAM. The recent study of LAM lung cell composition and novel LAM-relevant genetic animal model lay the groundwork for developing a novel mechanistic understanding of LAM pathobiology involving mTORC1-WNT signaling crosstalk and provide essential steps towards expending the repertoire of effective therapies for this devastating disease.
研究兴趣
论文共 164 篇作者统计合作学者相似作者
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American journal of respiratory cell and molecular biologyno. 1 (2024): 8-10
Susan M. Lin,Ryan Rue,Alexander R. Mukhitov, Akansha Goel,Maria C. Basil,Kseniya Obraztsova,Apoorva Babu,Slaven Crnkovic, Owen A. Ledwell,Laura T. Ferguson,Joseph D. Planer,Ana N. Nottingham,
JOURNAL OF CLINICAL INVESTIGATIONno. 4 (2024)
Ryan M. Powell,Jiri C. Moravec, Greg T. Jones,Basharat Bhat,Susan M. Lin,Joseph D. Planer,Vera P. Krymskaya,Edward Cantu,Sharon Pattison,Ian M. Morison, Bronwyn Gray,Michael R. Eccles,
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGYno. 1 (2024): 81-84
European Respiratory Reviewno. 169 (2023): 230100-230100
K. Obraztsova,A. R. Mukhitov,R. Rue, S. M. Lin, M. Basil,J. Carl,M. Morley,A. Babu, E. E. Morrisey,V. P. Krymskaya
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2023)
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Vera Krymskaya, Kseniya Obraztsova, Alexander Mukhitov, Ryan Rue, Akansha Goel, Apoorva Babu, Michael Morley, Edward Morrisey, Susan Lin, Jillian Evans
EUROPEAN RESPIRATORY JOURNAL (2023)
Andrii Kovalenko, Andres Sanin,Kosmas Kosmas,Long Zhang, Ji Wang,Elie W. Akl,Krinio Giannikou,Clemens K. Probst, Thomas R. Hougard,Ryan W. Rue,Vera P. Krymskaya,John M. Asara,
crossref(2023)
Andrii Kovalenko, Andres Sanin,Kosmas Kosmas,Long Zhang, Ji Wang,Elie W. Akl,Krinio Giannikou,Clemens K. Probst, Thomas R. Hougard,Ryan W. Rue,Vera P. Krymskaya,John M. Asara,
crossref(2023)
Sinem Koc-Gunel,Lalit K Gautam,Ben A Calvert, Shubha Murthy,Noa C Harriott, Janna C Nawroth,Beiyun Zhou,Vera P Krymskaya,Amy L Ryan
bioRxiv : the preprint server for biology (2023)
Andrii Kovalenko, Andres Sanin,Kosmas Kosmas,Long Zhang, Ji Wang,Elie W. Akl,Krinio Giannikou,Clemens K. Probst, Thomas R. Hougard,Ryan W. Rue,Vera P. Krymskaya,John M. Asara,
crossref(2023)
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