I lead a research laboratory focusing on investigation of the role of tumor suppressor proteins tuberin (TSC2) and hamartin (TSC1) in steroid action, cell survival, cellular metabolism, tumorigenesis and metastasis, and signaling transduction pathways.
My laboratory also develops animal models to test the efficacy of FDA approved drugs on the progression and metastasis of mTORC1 hyperactive cells, lung inflammation and injury. Current studies include determining the role of estrogen in the progression
of lymphangioleiomyomatosis (LAM), a female predominant rare lung disease, from the alteration of signaling pathways, to the integrity of alveolar epithelium and microenvironment in the lung, and to the pulmonary functions. We are also investigating
the potential application of using bloodbased biomarkers in LAM. Our research has been funded by NIH/the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Department of Defense and
the LAM Foundation. My laboratory developed the first LAM-associated, patient-derived primary cell line and the first metastatic model of LAM. We also have identified mTORC1-independent but mTORC2-mediated activation of prostaglandin biosynthesis
in TSC and LAM, and used metabolomics profiling to identify dysregulation of glucose metabolism and pentose phosphate pathway addiction in TSC2-deficient cells.
Specialized equipment available for collaborative research includes the IVIS Spectrum pre-clinical in vivo imaging system. I’m currently collaborating with Frank McCormack, MD, who provides access to human samples from patients with rare lung diseases;
Darcy Krueger, MD, PhD, and David Neal Franz, MD, on studying tuberous sclerosis complex (TSC) neurologic manifestation; Brian Siroky, PhD, on investigating TSC renal abnormalities; and Jiang Wang, MD, PhD, El Mustapha Bahassi, PhD, and Nagla Abdel
Karim, MD, PhD, on dissecting the interplay of steroid hormone receptors, autophagy and lung cancer.
Potential project for fellows: Interaction of pro-apoptotic protein Bim and estrogen on LAM cells in vitro and in vivo. Research skills acquired: Animal
handling, cell culture, molecular biology techniques. Training required or time delay: IACUC (animal) training, laboratory specific training, learning lab techniques.
Potential project for fellows: Altered MEK signaling affects lung LAM cell infiltration in an in vivo mouse model. Research skills acquired: Animal handling,
in vivo imaging (IVIS). Training required or time delay: IACUC (animal) training, laboratory specific training, learning lab techniques.