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.