DF/HCC Program Affiliation

Lung Cancer
Neuro-Oncology
Cancer Genetics, Leader

DF/HCC Associations

Member, Center Scientific Council
Co-Director, High-Throughput Polymorphism Detection

Research Abstract

• I have three areas of cancer interest. The first interest is the human genetic disease tuberous sclerosis. This is a tumor suppressor gene syndrome characterized by development of hamartomas in multiple organs, including brain, skin, lungs, and kidneys. My lab has made several seminal discoveries in this disorder over the past 20 years, including identification of the TSC1 gene. We are interested in the human molecular genetics of this syndrome, the biochemical activities of the protein products of the TSC1 and TSC2 genes including regulation of mTORC1, developing authentic mouse models of the disease using null and conditional alleles, testing therapies, and analysis of other genetic events occurring in the major tumors in this condition, angiomyolipoma of the kidney and lymphangioleiomyomatosis. We’re also interested in the role of these genes in cancer in general. The second interest is in thoracic oncology, particularly lung cancer. I see patients within the Thoracic Oncology Program at DFCI/BWH, and frequently participate in clinical trials. The third interest is in the development of cancer mutation testing at the Partners Center for Personalized Genetic Medicine (PCPGM) to enable personalized cancer medicine. I serve as the academic Director of Genotyping and Sequencing at the PCPGM, and as Leader of the Cancer Genetics program of the DF/HCC.

Publications

• Meikle L, Talos DM, Onda H, Pollizzi K, Rotenberg A, Sahin M, Jensen FE, Kwiatkowski DJ.A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival.J Neurosc
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• 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 Mar;117(3):730-8.
  17290308
• 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 correlation
  17287951
• Feng Y, Chen MH, Moskowitz IP, Mendonza AM, Vidali L, Nakamura F, Kwiatkowski DJ, Walsh CA.Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis.Proc Natl Acad Sci U S A 2006 Dec 26;103(52):19836-41.
  17172441
• Vidali L, Chen F, Cicchetti G, Ohta Y, Kwiatkowski DJ.Rac1-null mouse embryonic fibroblasts are motile and respond to platelet-derived growth factor.Mol Biol Cell 2006 May;17(5):2377-90.
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