Member, Whitehead Institute
Professor of Biology, MIT
Investigator of the Howard Hughes Medical Institute
Senior Associate Member, Broad Institute
Member, David H. Koch Institute for Integrative Cancer Research at MIT
Whitehead Member David Sabatini studies the mechanisms that regulate cell growth. Spurred by the discovery of a cellular pathway that helps switch cell growth on and off, research in the Sabatini lab has linked growth to a cell’s ability to sense nutrients in its environment.
This growth-triggering system, known as the TOR (target of rapamycin) pathway, is composed of a complex of proteins that respond to nutrient cues. Sabatini is working to identify TOR pathway components and study how they work and interact. His efforts to understand mammalian TOR at the cellular level have provided a new way to investigate the role nutrients and metabolism play in disease.
Rapamycin, an immunosuppressant that inhibits cell growth via the mTOR pathway, was first used to prevent organ rejection in kidney transplant patients. Today, it is employed as a drug as well as a research tool. As a graduate student and later as a Whitehead Fellow, Sabatini exposed cells to rapamycin and monitored its effect on TOR. Using this approach, Sabatini has identified several of the proteins that comprise the mammalian TOR (mTOR) complex.
Several years ago, Sabatini discovered a protein that stabilizes interactions between two other mTOR components. The balance between these protein components might be perturbed in human disease and could be a potential target for therapy. This seems to be the case in tumors caused by tuberous sclerosis (TS), a genetic disease that causes growth of benign tumors throughout the body. In TS tumors the TOR pathway malfunctions, cell growth goes unchecked and cells become very large. Sabatini is screening various cancers to find others that result from dysfunctional mTOR activity and may respond to rapamycin therapy.
Recently, Sabatini’s lab discovered that a family of proteins known as Rag proteins controls where mTOR sits in the cell and how it responds to nutrients, signaling the cell to grow.
To study TOR, Sabatini needed to examine gene and protein function in thousands of living cells all at once, in real time. Because this was not possible with existing technology, Sabatini and colleagues invented a cell microarray that allows them to do just that.
Sabatini was appointed a Whitehead Fellow in 1997 after completing the MD/PhD program at Johns Hopkins University School of Medicine. Sabatini was named an Associate Member at Whitehead and an Assistant Professor in the biology department at MIT in 2002. He was appointed a Professor at MIT and a Howard Hughes Medical Institute Investigator in 2008.
- Developed and patented novel cell microarray process
- Identified component parts of cell growth protein complex implicated in diseases such as cancer
- Named one of the world’s 100 Top Young Innovators by Technology Review
- Charles Ross Scholar at MIT (2003)
- Pew Scholar in the Biomedical Sciences (2003)
- Rita Allen Fellowship (2004)
- Paul Marks Prize (2009)
- Member of the National Academy of Sciences (2016)