Section: Research

Postdoctoral Position Available

Michael Brodsky, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Program in Gene Function and Expression
   Program in Molecular Medicine

Other Affiliation(s):
   Interdisciplinary Graduate Program

Drosophila p53 and DNA Damage-Induced Apoptosis

The overall goal of the lab is to understand how animal cells coordinate cell proliferation and cell death during development. To approach this problem, we are studying the regulation of apoptosis and cell cycle arrest following DNA damage in the fruit fly Drosophila melanogaster. In normal human cells, the p53 transcription factor helps regulate DNA damage-induced apoptosis, partly explaining why p53 is the most frequently mutated gene in human cancer cells. We have shown that a knockout of Drosophila p53 completely eliminates DNA damage-induced transcription and apoptosis (see figure), demonstrating that p53 function has been conserved from insects to mammals. By studying the function of fly p53, we hope to better understand how apoptosis is regulated during normal development and during tumor development.

We are using a combination of genetics, microarrays, and informatics to identify and characterize new regulators and targets of Drosophila p53. Using Affymetrix microarrays, we have identified multiple transcriptional targets of Drosophila p53 including regulators of apoptosis such as reaper and cell-cell signaling molecules such as the Drosophila homolog of Tumor Necrosis Factor. Using genetic analysis, we have identified several genes required for DNA damage-induced apoptosis or cell cycle arrest. Characterization of these genes should provide new insights into how animal tissues respond to DNA damage. As we come to understand how p53 regulates the response to DNA damage, we will explore the mechanisms that determine why only a subset of cells exposed to DNA damage enter the apoptotic pathway and how developmental signals influence that decision.

Office: 623
Phone: 508-856-1640
E-mail: Michael.Brodsky@umassmed.edu
Keywords: Oncogenes/tumor suppressors, Chromosome Structure & Dynamics, Apoptosis, DNA Damage and Repair, Organisms - Drosophila

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Brodsky for additional details.