Daniel A. Haber


Department of Medicine
Massachusetts General Hospital East
Cancer Center
Building 149, 13th Street
Charlestown, MA 02129
Tel: (617) 726-7805
Fax: (617) 724-6919
Email: haber@helix.mgh.harvard.edu

11 postdoctoral fellows


Our laboratory is interested in the genetics of cancer, with primary emphasis on the identification and characterization of genetic targets for molecular-directed therapy and studies of the Wilms tumor suppressor pathways.

 

In searching for somatic genetic events that underlie cancer progression, we observed that non-small cell lung cancers with dramatic responses to the tyrosine kinase inhibitor gefitinib harbor mutations in the drug's target, the epidermal growth factor receptor (EGFR). We have shown that these mutations alter the function of the EGFR kinase domain, resulting in “oncogene addiction” of cancer cells to the EGFR pathway. We have extended these findings to search for additional mutationally activated drug targets in cancer, and understand the mechanisms underlying acquisition of drug resistance. Recently, we have tested a microfluidic device to capture circulating tumor cells (CTCs) from the blood of patients with cancer, to provide “real time” measurements of tumor cell genetic composition. These studies are opening the way for detailed analyses of metastatic precursors in the blood circulation and molecular pathways that may be of therapeutic relevance.

 

Wilms tumor is a pediatric kidney cancer that has been linked to both germline and somatic inactivation of the WT1 gene, encoding a zinc finger transcription factor. Expression of WT1 is required for development of the kidney, gonads, and mesothelial tissues.  Using a genome-wide screen, we recently identified a novel tumor suppressor gene on the X chromosome, WTX, whose “single hit” inactivation contributes to as many as 30% of sporadic Wilms tumor in males and females. Current studies are aimed at molecular characterization of this novel gene.

 

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BBS webpage updated 12/02/2009