Research Department

Medical Oncology/Molecular and Cellular

Area of Research

Biography

Dr. Brown received his MD from Johns Hopkins University in 1982, followed by an internal medicine residency at Brigham and Women's Hospital and a fellowship in medical oncology at DFCI. He conducted postdoctoral research at Massachusetts Institute of Technology from 1987 to 1990. In 1990, he opened his own lab at DFCI, where his molecular studies focus on the role of steroid hormone receptors and other transcription factors in cancer.

Recent Awards

• American Society for Clinical Investigation, 1997

Research

The steroid hormones estrogen and androgen play critical roles in the normal physiology of the breast and prostate and pathologic roles in breast and prostate cancers. The overall aim of our current research is to advance the molecular understanding of estrogen receptor (ER) and androgen receptor (AR) action to foster improvements in the prevention and treatment of breast and prostate cancers.

During the past few years, several laboratories, including our own, have identified many important coregulatory molecules that play a central role in mediating the transcriptional activity of ER and AR and help to explain the selectivity of drugs that target these receptors.

Most recently, we have been using a new technology that takes advantage of the completion of the sequencing of the human genome to identify all of the sites of ER and AR function. This so-called ChIP-on-chip approach (chromatin immunoprecipitation-on-a-chip) has already revealed important new insights into steroid receptor action and promises to identify important regulatory domains within the vast regions of unexplored sequence in the human genome.

Select Publications

• Carroll JS, Liu XS, Brodsky AS, Meyer CA, Li W, Szary AJ, Eeckhoute J, Shao W, Hestermann EV, Geistlinger TR, Fox EA, Silver PA, Brown M. Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell 2005;122:33-43.
• Hestermann E, Brown M. Agonist and chemopreventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor. Mol Cell Biol 2003;23:7920-25.
• Wang Q, Carroll JS, Brown M. Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Mol Cell 2005;19:631-42.
• Torres-Arzayus MI, Font de Mora J, Yuan J, Vazquez F, Bronson R, Rue M, Sellers WR, Brown M. High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer Cell 2004;6:263-74.
• Shao W, Keeton EK, McDonnell DP, Brown M. Coactivator AIB1 links estrogen receptor transcriptional activity and stability. Proc Natl Acad Sci U S A 2004;101:11599-604.
• Keeton EK, Brown M. Cell cycle progression stimulated by tamoxifen-bound estrogen receptor-alpha and promoter-specific effects in breast cancer cells deficient in N-CoR and SMRT. Mol Endocrinol 2005;19:1543-54.

Trainees

• Carroll, Jason, PhD
• Keeton, Erika, PhD
• Torres-Arzayus, Maria, PhD
• Geistlinger, Tim, PhD
• Krum, Susan, PhD
• Fertuck, Kirsten, PhD
• Lupien, Mathieu, PhD
• Wang, Qianben, PhD