Diane Fingar, PhD

Research in the Fingar lab focuses on a complex cellular signaling network centered on the evolutionarily conserved protein kinase mTOR (mechanistic target of rapamycin). mTOR functions as a nutrient sensor that acquired the ability during metazoan evolution to respond to additional diverse systemic cues such as hormones and growth factors. mTOR forms the catalytic core of two known multi-protein complexes, mTOR complex 1 (mTORC1) and mTORC2 that control fundamental cellular processes. Aberrant mTOR complex (mTORC) function contributes to myriad pathologic states including metabolic disorders such as type II diabetes, immunological and cardiovascular disorders, and cancer. Not surprisingly, mTORCs play critical roles in health and disease. Despite the clear physiologic and therapeutic importance of mTOR, fundamental gaps in knowledge exist in our understanding of mTORC regulation and function, especially about how mTORC networks communicate with other important signaling systems in cells and in vivo.

The Fingar lab focuses on identifying novel extra- and intra-cellular cues and mechanisms that regulate mTORC1 and mTORC2 signaling and how these events control downstream cellular processes. In particular, we have keen interest in understanding how site-specific phosphorylation regulates mTORC signaling and function in cultured and primary mammalian cells and in vivo using genetically modified mice. Through generation of phospho-specific antibodies, phospho-defective and -mimetic substitution mutants in cells and in mice, and kinome screening to identify the kinases and pathways that mediate site-specific phosphorylation, our work has revealed unexpected crosstalk between mTORCs and other important signaling systems. Detailed biochemical understanding of mTORC network wiring is essential for development of new therapies for patients afflicted with myriad mTOR-linked disorders.