1981 – B.A., University of Virginia, Charlottesville, VA (Philosophy)
1988 – Ph.D., Cornell University Graduate Schoole of Medical Sciences, New York, NY (Viral Oncology)
1989 – M.D., Cornell University Medical College, New York, NY (Medicine)
Residency: Brigham and Women’s Hospital, Boston, MA.
Fellowship: Medical Oncology/Molecular Medicine, FHCRC and University of Washington
The Clurman lab studies the pathways that regulate cell growth and division. Our goals are to understand the molecular mechanisms that drive tumorigenesis and to develop new cancer therapies. We work in two general areas: 1) cellular regulation by the ubiquitin-proteasome system, and 2) control of cell division by cyclin-dependent kinases (CDKs).
One of our major interests is the Fbw7 tumor suppressor, a ubiquitin ligase that is mutated in nearly 10% of all cancers. Examples of our recent work in this area include:
- New understanding of how Fbw7 recognizes its targets and the consequences of Fbw7 mutations in cancer (Welcker et al., Genes and Development, 2013)
- The identification of new Fbw7 substrates that may contribute to tumorigenesis (Davis et al., Genes and Development, 2013)
- The development of a new mouse model of advanced colon cancer caused by Fbw7 mutations (Grim et al., Molecular and Cellular Biology, 2012).
Mutations in the genes that regulate the cell cycle are among the most common genetic changes in cancers.
- We study how CDKs regulate cell division, how they contribute to tumorigenesis, and how abnormal CDK regulation in cancers can be therapeutically exploited. Examples of this work include:
- New methods to identify and study CDK targets (Chi et al, Genome Biology, 2008, Hizli et al, Molecular and Cellular Biology, 2013).
- Demonstration of the essential role of CDK2 inhibition in cellular responses to replication stress (Hughes et al., PNAS, 2013).
- Development of human and murine gene-targeting models to study cyclin E functions in cell division and genome stability (Grim et al., J Cell Biology, 2008, Minella et al, Genes and Development, 2008).
I am a Medical Oncologist specializing in all aspects of hematopoietic stem cell transplantation.
- Development of novel drug therapy targeting mutant ubiquitin ligases in cancer
- Therapeutic targeting of replication stress failure in cancer cells with aberrant CDK2 activity
- New mouse models of Fbw7- and cell cycle-associated cancer
- Bioinformatic and high-throughput approaches to identify therapeutic targets in cell cycle- and Fbw7-associated cancers