DF/HCC Program Affiliation

Leader, Cancer Genetics Program
Member, Neuro-Oncology Program
Member, Lung Cancer Program

DF/HCC Associations

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

Research Abstract

I have three cancer-related interests. The first interest is the human genetic disease tuberous sclerosis. It is a tumor suppressor gene syndrome characterized by development of hamartomas in multiple organs, including brain, skin, lungs, and kidneys. We are interested in the human molecular genetics of this syndrome, the biochemical activities of the protein products of the TSC1 and TSC2 genes, characteristics of cells lacking either one of these gene products, and in developing mouse models of the disease using null and conditional alleles with tissue-specific targetting. The second interest is in the pathogenesis and treatment of lung cancer. I am interested in understanding why lung cancer develops in some patients at a young age, and with relatively littel tobacco exposure. I am also interested in the role of the TSC1 and TSC2 genes in lung cancer. The third interest is in the clinical care of lung cancer patients. I see patients within the Thoracic Oncology Program at DFCI/BWH, and frequently participate in clinical trials. I also serve as the Director of the Harvard-Partners Center for Genetics and Genomics Genotyping Facility, and Leader of the Cancer Genetics program of the DF/HCC.

Publications

• Kozlowski P, Bissler J, Pei Y, Kwiatkowski DJ. Analysis of PKD1 for genomic deletion by multiplex ligation-dependent probe assay: Absence of hot spots. Genomics 2007 Nov 28;
  PMID: 18060739
• Finlay GA, Malhowski AJ, Liu Y, Fanburg BL, Kwiatkowski DJ, Toksoz D. Selective inhibition of growth of tuberous sclerosis complex 2 null cells by atorvastatin is associated with impaired Rheb and Rho GTPase function and reduced mTOR/S6 kinase activity. Cancer Res 2007 Oct 15; 67(20):9878-86
  PMID: 17942919
• Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC. LKB1 modulates lung cancer differentiation and metastasis. Nature 2007 Aug 16; 448(7155):807-10
  PMID: 17676035
• 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 Neurosci 2007 May 23; 27(21):5546-58
  PMID: 17522300
• 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
  PMID: 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 correlations. Hum Genet 2007 May; 121(3-4):389-400
  PMID: 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
  PMID: 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
  PMID: 16525021