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 pulmonary function. We are also investigating the potential application of using blood-based biomarkers in LAM. 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.