Signaling in Mammalian Cell Growth and Differentiation
Our laboratory is interested in understanding signal transduction mechanisms that underlie fundamental cellular and developmental processes in mammals. We employ a wide range of experimental approaches from molecular biology, biochemistry, single-molecule biophysics, to cell biology and animal models.
mTOR Signaling Network
The mammalian target of rapamycin (mTOR), a member of the phosphatidylinositol kinase-related Ser/Thr protein kinase family, assembles a signaling network that is a master regulator of cell growth, proliferation, differentiation, and metabolism. The mTOR network senses the availability of nutrients (amino acids, in particular), and integrates other types of environmental cues, including growth factors, cellular energy levels, and various types of stress. Rapamycin, an exquisitely specific inhibitor for mTOR, is a bacterial macrolide that has tremendous clinical values. Rapamycin and its analogs have been approved by the FDA for three types of clinical use – as an immunosuppressant to prevent graft rejection after transplantation, an anti-restenosis agent used in angioplasty stenting, and an anti-cancer drug. Over the years we have uncovered regulators and pathways in the mTOR signaling network, and we continue to discover novel mechanisms and complexities of this signaling. These efforts will not only advance our understanding of cellular regulation, but also facilitate the future design and improvement of therapeutic strategies.
Myogenic Differentiation and Skeletal Muscle Regeneration
Another focus in our lab is the molecular mechanisms governing skeletal muscle development and regeneration. In the experimental systems of myoblast differentiation in vitro and muscle development and regeneration in mice, we interrogate the molecular wiring that controls the highly coordinated cellular events leading to the formation of multi-nucleated myofibers. Our findings have revealed a central role of mTOR in assembling pathways that regulate various stages of myogenesis, distinct from those that control cell growth. In addition, we have dissected the mechanisms of regulation by myogenic microRNAs. Our current efforts are also focused on myocyte-secreted cytokines and their signaling that critically contribute to myogenic differentiation in vitro and muscle regeneration in vivo. Knowledge gained may shed light on potential future targets for treating aging- or disease-related muscular atrophy and dystrophy.
Single-Molecule Analysis of Protein Complexes and Lipid-Protein interactions