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David A. Frank, MD, PhD

Associate Professor, Department of Medicine, Harvard Medical School

Associate Professor of Medicine, Medical Oncology, Dana-Farber Cancer Institute

Associate Physician, Medicine, Oncology, Brigham And Women's Hospital

Contact Info

David Frank
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA, 02215
Mailstop: Mayer 522B
Phone: 617-632-4714
Fax: 617-632-6356
david_frank@dfci.harvard.edu

Assistant

Not Available.

DF/HCC Program Affiliation

Kidney Cancer
Lymphoma and Myeloma

Research Abstract

Our group focuses on the intracellular signaling events that control the growth and differentiation of normal and malignant cells. Extracellular stimuli lead to a cascade of events which culminates in the regulation of gene expression. It is the activation or repression of specific genes that then determines cellular function. We study how these signaling events occur normally in response to cytokines, hormones, and cell-cell interactions by examining the activation of kinase cascades, transcription factors, and key target genes. Among the mediators we have focused on are STAT transcription factors, which can be modulated by both tyrosine and serine phosphorylation, and thus may serve as a convergence point for multiple signaling pathways.



One of the hallmarks of malignancy is the ability of cells to grow independent of external signals. Given this, we have extended our work to analyze the activation of intracellular signaling pathways in primary tumor cells and in models of human malignancies. We have found that STATs and other signaling pathways are activated inappropriately in many forms of cancer. Furthermore, we are identifying the specific target genes that mediate the ability of STATs to lead to malignant transformation of cells. Utilizing bioinformatics techniques, we have been able to identify a genetic signature in primary human tumor cells reflecting STAT activation. This work has shed light both on the pathogenesis of these diseases and on critical regulators of the growth of normal cells. An additional control point in the development of malignancies is angiogenesis, the growth of new blood vessels to support the tumor. We have found that STAT transcription factors play an important role in endothelial cell function, and thus understanding this signaling pathway can reveal insights into many aspects of cancer biology.



Finally, we are developing targeted molecular inhibitors of STATs and other transcription factors using both rational design and chemical-biology approaches. These reagents are useful tools for dissecting the roles of signaling pathways in the growth and differentiation of normal cells. Furthermore, given the inappropriate activation of signaling pathways in malignant cells, these approaches may be useful in developing novel therapeutic strategies for the treatment of cancer.

Publications

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