Dr. David Sabatini is a Member of the Whitehead Institute for Biomedical Research, and a Professor of Biology at the Massachusetts Institute of Technology. He is also an Investigator of the Howard Hughes Medical Institute, a Senior Associate Member at the Broad Institute, a member of the Koch Institute for Integrative Cancer Research, and an American Cancer Society Research Professor. Dr. Sabatini and his lab study the basic mechanisms that regulate cell growth. A major focus of the lab is the Target of Rapamycin (TOR) pathway, a major regulator of growth in many eukaryotic species. This has resulted in the identification of many components of the pathway and to an understanding of their cellular and organismal functions, most of which have implications for diseases such as cancer and diabetes. David is also interested in the role of metabolism in cancer and in the mechanisms that control the effects of dietary restriction on tumorigenesis. Additionally, his lab has developed new technologies that facilitate the analysis of gene function in mammalian cells.

Regulation of mTOR by nutrients

mTOR is the target of the immunosuppressive and anti-cancer drug rapamycin and the central component of a nutrient- and hormone-sensitive signaling pathway that regulates cell growth and proliferation. We now appreciate that this pathway becomes deregulated in many human cancers and has key roles in the control of metabolism, cell and organ size, and aging. We have identified two distinct mTOR-containing proteins complexes, one of which regulates growth through S6K and another that regulates cell survival and metabolism through Akt. These complexes, called mTORC1 and mTORC2, define both rapamycin-sensitive and insensitive branches of the mTOR pathway. Over the last few years we have focused on how nutrients, particularly amino acids, regulate mTORC1. We have identified a complex signaling pathway that relays amino acid availability to mTORC1 through the heterodimeric Rag GTPases. We recently discovered several of the amino acid sensors for the pathway. I will discuss new results from our lab on the regulation and functions of mTORC1.