David J. Kwiatkowski

Department of Medicine
Brigham & Women's Hospital
Genetics Laboratory, Translational Medicine Division
Karp Building, Room 6-216
1 Blackfan Circle
Boston, MA 02115
Tel: (617) 355-9005
Fax: (617) 355-9016
Email: dk@rics.bwh.harvard.edu

We are interested in the tumor suppressor gene syndrome tuberous sclerosis, and the functions of its causative genes, TSC1 and TSC2. We pursue studies on the human molecular genetics of this disease, develop mouse models using null and conditional alleles of TSC1 and TSC2, explore biochemical and signaling pathways, and explore therapeutic approaches. There is a particular interest in the generation of brain models of this disorder. A second major interest is lung cancer genetics. We are developing assays for the detection of clinically relevant mutations in lung cancer specimens, and are exploring the role of the TSC genes in lung cancer development.

Research approaches in common use in my lab include DNA variation detection, automated sequencing, generation of conventional and conditional mouse knock-outs, primary cell culture, protein analysis and immunoblotting, signaling pathway analysis, and high throughput genotyping. I am Director of the Brigham and Women's Hospital DNA Sequencing Core Facility, and Director of the Harvard Partners Center for Genetics and Genomics Genotyping Facility.

References:

• Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, Kwiatkowski DJ. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008 28:5422-32.

• Pollizzi K, Malinowska-Kolodziej I, Doughty C, Betz C, Ma J, Goto J, Kwiatkowski DJ. A hypomorphic allele of Tsc2 highlights the role of TSC1/TSC2 in signaling to AKT and models mild human TSC2 alleles. Hum Mol Genet 2009 18:2378-87.

• Lee PS, Tsang SW, Moses MA, Trayes-Gibson Z, Hsiao LL, Jensen R, Squillace R, Kwiatkowski DJ. Rapamycin-insensitive Up-regulation of MMP2 and Other Genes in TSC2-deficient LAM-like Cells. Am J Respir Cell Mol Biol. 2009 in press.