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 broadly in the use of genetic approaches to understand human disease. One major interest is the tumor suppressor gene syndrome tuberous sclerosis. 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:

• Zhang H, Bajraszewski N, Wu E, Wang H, Moseman AP, Dabora SL, Griffin JD, Kwiatkowski DJ. PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. J Clin Invest. 2007 117:730-738.

• Kozlowski P, Roberts P, Dabora S, Franz D, Bissler J, Northrup H, Au KS, Lazarus R, Domanska-Pakiela D, Kotulska K, Jozwiak S, Kwiatkowski DJ. Identification of 54 large deletions/duplications in TSC1 and TSC2 using
  MLPA, and genotype-phenotype correlations. Hum Genet. 2007 121:389-400.

• Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, Kwiatkowski DJ. Response of a neuronal model of tuberous sclerosis to mTOR inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neuroscience. 2008, in press.