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, and understanding how the brain-related manifestations (seziures, autism, cognitive delay) occur. There is also particular interest in the role of the TSC1 and TSC2 genes and other genetic changes that occur in the tumor syndromes that occur in TSC, including renal angiomyolipomas, pulmonary lymphangioleiomyomatosis, and subependymal giant cell astrocytoms. There is also an interest in the role of the TSC genes in the common adult malignancies, especially bladder cancer.
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 sequencing and 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, and a visiting scientist at the Broad Institute.
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.
- Qin W, Kozlowski P, Taillon BE, Bouffard P, Holmes AJ, Janne P, Camposano S, Thiele E, Franz D, Kwiatkowski DJ. (2010) Ultra deep sequencing detects a low rate of mosaic mutations in tuberous sclerosis complex. Hum Genet. 2010 Mar;127(5):573-82 PMID: 20165957.
- Kwiatkowski DJ, Thiele EA, Whittemore VH, editors. Tuberous sclerosis complex. 2010, Weinheim, Germany: Wiley-VCH. 409p.
For a complete listing of publications on PubMed, click here.
BBS webpage updated 6/14/2010

