David Kwiatkowski, M.D.

Professor of Medicine

Brigham & Women’s Hospital
Harvard Medical School
One Blackfan Circle
Karp Family Research Building, 6th Floor
Boston, MA 02115

Tel 617 355 9005
Fax 617 355 9016
dk@rics.bwh.harvard.edu

> Selected Papers


Research Overview
I am a human and molecular geneticist. A major research interest area is the human genetic disease and tumor suppressor gene syndrome tuberous sclerosis (TSC). There is a broad interest in the human molecular genetics of TSC, including defining the spectrum of disease, the identification of potential additional genes and modifier genes, the rate of mosaicism and clinical implications, and the correlation between mutation types and clinical phenotype. There is also a major interest in defining the pathogenesis of disease manifestations occurring in TSC, including understanding how renal angiomyolipoma, pulmonary lymphangioleiomyomatosis, and cortical tubers develop, as these are the cause of the major morbidity and mortality that is seen in TSC patients. Other genetic changes that occur in the tumors that arise in TSC patients are also of interest.

The biochemical and physiological function of the TSC1 and TSC2 proteins is also a major interest. Development of mouse models of tuberous sclerosis and in particular using conditional alleles with tissue specific-cre recombinase expression to develop authentic models of human tuberous sclerosis is also a major interest. There is a particular focus on models of the renal, lung and brain lesions. These mouse models are useful both in the exploration of disease pathogenesis and in therapeutic trials. We are also interested in the functions of the TSC1 and TSC2 genes in the common human malignancies, particularly lung cancer.

A second major interest is genomic technologies and their use for analysis of both germline and somatic mutations. This is related in part to the interest in the human molecular genetics of TSC. This interest also extends to the use of genomic approaches for the evaluation of somatic changes associated with cancer, and translation of these methods to clinical application.