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David J. Kwiatkowski, MD, PhD

Professor, Department of Medicine, Harvard Medical School

Senior Physician, Medicine, Brigham And Women's Hospital

Medical Oncologist, Thoracic Oncology Program, Dana-Farber Cancer Institute

Contact Info

David Kwiatkowski
Brigham And Women's Hospital
1 Blackfan Circle
Boston, MA, 02115
Mailstop: Rm 6-213
Phone: 617-355-9005
Fax: 617-355-9016
dk@rics.bwh.harvard.edu

Assistant

Donna Hallissey
Unit Administrator for Translational Medicine
Brigham And Women's Hospital
Phone: 617-355-9001
dhallissey@partners.org

DF/HCC Program Affiliation

Lung Cancer
Cancer Genetics, Leader

DF/HCC Associations

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

Research Abstract

A major research interest is the tumor suppressor gene syndrome Tuberous Sclerosis (TSC), and the functions of its causative genes, TSC1 and TSC2. We identified the TSC1 gene in 1997, have made mouse models of both Tsc1 and Tsc2, and have derived cell lines (MEFs) that are deficient in these genes, that are widely used by investigators studying signaling. 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 therapeutic approaches. There is a particular interest in the pathogenesis of all of the tumors that occur in this disease, including lymphangioleiomyomatosis (LAM), angiomyolipomas, subependymal giant cell astrocytomas, and renal carcinoma.
Recently it has become apparent that a variety of cancers (bladder carcinoma, renal cell carcinoma, pancreatic NET, PEComas) have mutations in TSC1 or TSC2 at rates of 1 – 10%. Moreover, in some cases TSC1/TSC2-mutant cancers are highly sensitive to treatment with rapalogues, with durable CRs lasting over 2 years in some cases of bladder and renal cell carcinoma. We intend to study these patients to elucidate the precise determinants of response to rapalogues, and investigate synergistic treatment approaches. I am the PI of a Novartis-sponsored Investigator-initiated trial to treat all cancers with mutations in either TSC1 or TSC2 with everolimus. A variety of correlative genetic studies will be done as part of that trial.
I have a general interest and expertise in molecular genetics. I have run or co-directed DNA analysis and diagnostic laboratories for many years. I am an Associate Member in the Broad Institute cancer genome analyses programs, and have several projects ongoing there.

Publications

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