For elucidating the role of steroid hormones and their receptors in promoting the onset and progression of various hormone-dependent malignancies and for the discovery of regulatory complex components such as the p160 class of transcriptional co-activators that facilitate the epigenetic regulation of steroid receptor activity.
A distinguished leader in the cancer research community, Dr. Brown has elucidated the role of steroid hormones and their receptors in promoting the onset and progression of various hormone-dependent malignancies including breast and prostate cancer. Specifically, his research has highlighted the important role of hormones such as estrogen and progesterone in normal physiology as well as tumorigenesis, research which has resulted in improved understanding of the regulatory mechanisms that govern hormone signaling. His related work involving the estrogen receptor (ER) has also resulted in the discovery of regulatory complex components such as the p160 class of transcriptional co-activators that facilitate the regulation of steroid receptor activity. This discovery led to the understanding of how activation of downstream transcription targets of ER occurs. Using chromatin immunoprecipitation (ChIP), Dr. Brown and his colleagues identified protein-protein interactions at ER-responsive promoter regions. Specifically, interactions with the p160 class of co-activators were demonstrated to be sufficient for gene activation, leading to growth stimulation of cancer cells. These studies also demonstrated that tamoxifen administration can lead to the recruitment of co-repressors to these same promoter regions, as opposed to co-activators.
Importantly, identification of such coregulators has demonstrated their necessity to induce robust ER-mediated transcriptional activity. In a seminal publication, Dr. Brown not only identified the coregulators, but also described the sequence in which these proteins are recruited to and disassembled from the estrogen receptor. In subsequent studies, Dr. Brown and colleagues discovered that these coregulatory proteins bind to sites distally located to promoter regions, termed enhancers. This study represented the first genome wide study of its kind to identify regulatory regions that influence the transcription of downstream targets. Dr. Brown has also studied the interactions between the ER and p53, and how this prevents p53-mediated cell death in ER-positive breast cancer. He has also characterized the role that androgens play in ER-negative/HER2-positive breast cancer. Collectively, Dr. Brown’s seminal research findings have significantly contributed to the understanding of endocrine-based therapies and therapeutic resistance.
Selected Awards and Honors
2019 AACR Distinguished Lectureship in Breast Cancer Research, American Association for Cancer Research, Philadelphia, Pennsylvania
2018 Elected Member, National Academy of Science, Washington, DC
2017 Elected Fellow, Academy of Arts and Sciences, Washington, DC
2015 Brinker Award for Scientific Distinction in Basic Science, Susan G. Komen®, Dallas, Texas
2010 Edwin B. Astwood Award Lecture, Endocrine Society, Washington, DC
2006 Tisch Family Outstanding Achievement Award, Dana Farber, Boston, Massachusetts
2005 North American Menopause Society- Wyeth Pharmaceuticals Selective Estrogen-Receptor Modulators (SERMs) Research Award, Cleveland, Ohio
2003 Elected Member, Association of American Physicians, Belleville, Michigan
1997 Elected Member, American Society for Clinical Investigation, Ann Arbor, Michigan