BBS Faculty Member - David Kwiatkowski

David Kwiatkowski

Department of Medicine
Division of Pulmonary and Critical Care Medicine and of Genetics

Brigham and Women's Hospital
Karp Building, Room 6-216
1 Blackfan Circle
Boston, MA 02115
Tel: 617-355-9005
Fax: 617-355-9016

My major research interest is the tumor suppressor gene syndrome tuberous sclerosis (TSC), its causative genes TSC1 and TSC2, and their role in signaling and tumor development. We identified the TSC1 gene in 1997, have made numerous mouse models of both Tsc1 and Tsc2, and performed signaling and preclinical therapeutic studies that enabled the clinical use of rapamycin and analogues in this disease. I was the lead editor for the definitive book on this disorder: Tuberous sclerosis complex: Genes, Clinical Features, and Therapeutics (Wiley, 2010). We pursue studies on the human molecular genetics of TSC, develop novel mouse models using conditional alleles of TSC1 and TSC2, explore biochemical and signaling pathways and therapeutic approaches. There is a particular interest in the pathogenesis of all of the tumors that occur in this disease, including lymphangioleiomyomatosis (LAM), angiomyolipomas, PEComas, and subependymal giant cell astrocytomas.

We are also interested in non-TSC cancers in which mutation of the TSC1/TSC2 genes is a driver event, and development of therapeutic strategies for these cancers. Recently mutations in these genes have been identified in diverse cancers, and some of the tumors with TSC1/TSC2 mutations are very sensitive to treatment with rapamycin and other inhibitors. We are studying the genetic basis of response and subsequent resistance development. In aggregate TSC1/TSC mutations are seen in about 2-3% of all human cancer, so that improved therapies and understanding would have a broad therapeutic impact. We are working in particular on bladder cancer, clear cell RCC, chromophobe kidney cancers, and anaplastic thyroid cancer.

Research approaches in common use in my lab include DNA variation detection, next gen sequencing analysis, computational methods for analysis of NGS data, CRISPR for genome editing, both inactivation and activating mutations, primary cell culture, protein analysis and immunoblotting, signaling pathway analysis, and development of mouse models. I am Director of the Brigham and Women's Hospital DNA Sequencing Core Facility, Assistant Director of the Partners Center for Personalized Genetic Medicine, an Associate member of the Broad Institute, and Leader of the Dana Farber/Harvard Cancer Center Cancer Genetics Program.

Last Update: 8/4/2015


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