David M. Livingston

Harvard University

Election Year: 1995
Primary Section: 41, Medical Genetics, Hematology, and Oncology
Membership Type: Member

Research Interests

As a scientist, my abiding interest has been the biochemical mechanisms which lead normal cells to exhibit malignant behavior. My work began with an effort to understand how the primary oncoprotein (large T antigen) of the tumor virus, SV40, transforms cells. Our research was marked by the first complete purification of this protein and the identification of central elements in its biological and biochemical behavior. In recent years, we found that it operates as a transforming element, in part, by binding and specifically perturbing the behavior of a tumor suppressing gene product dedicated to growth control (pRB). It also interacts with and disorders the behavior of yet other growth and differentiation control proteins, two of which were cloned in our laboratory. These findings have led to the elucidation of key elements of complex molecular pathways which contribute to normal growth and differentiation. Indeed, one of these pathways, at the center of which is pRB, is disrupted in nearly all human tumors. We are now trying to understand how disorderly function of one or more of these pathways translates into major malignant characteristics of certain common epithelial neoplasms. In addition, we have begun to study the mechanisms by which the tumor suppressor genes, BRCA1 and 2, operate.

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