920 Biomedical Research Tower
460 West 12th Avenue
Columbus, OH 43210
Steroid hormones signal throughout the body to regulate various physiological processes. These steroids interact with proteins called nuclear receptors that act as transcription factors to bind DNA and initiate a cascade of events leading to the activation or repression of target genes. The process of turning on nuclear steroid receptors is tightly controlled through a variety of molecular mechanisms. These mechanisms of control are frequently deregulated in cancer. My group focuses on understanding the molecular mechanisms which govern receptor activity and delineating how these processes are deregulated in cancer.
A particular interest of my group is the potential of environmental compounds known as endocrine disruptors to influence estrogen receptor activity. Estrogens are steroids that are able to activate the estrogen receptor. Both man-made, industrial chemicals, such as bisphenol A, and naturally occurring plant compounds found in our diet are able to mimic estrogens and activate the estrogen receptor.
Exposure to environmental estrogens during early life can reprogram the mammary gland increasing the potential for cancer development in adulthood. This phenomenon represents a window of susceptibility during development in which estrogenic exposures may carry increased risks. The pathology associated with these windows of susceptibility usually present well after the exposure and suggests permanent and epigenetic alteration to the affected tissues. My group is using rodent models of in utero exposure to understand the mechanistic pathways by which environmental compounds may initiate epigenetic changes in the mammary gland that lead to altered morphology and an increased risk of breast cancer.
Estrogen in melanoma
Several lines of evidence suggest that estrogen action may play a protective role against melanoma development. For instance, men are more likely to be diagnosed and die of the disease. Furthermore, loss of estrogen receptor beta expression correlates with increase disease progression. My group is using both mouse models and mammalian cell culture approaches to understand how estrogen receptor beta activity may act in melanocytes and the immune system to prevent melanoma initiation and progression.
Estrogenic control of breast cancer proliferation
A third area of interest in my group is aimed at understanding how the estrogen receptor controls proliferation of breast cancer. The majority of breast cancers rely on estrogen receptor activity for growth and survival. For this reason, patients receive hormone therapy aimed at inhibiting the estrogen receptor. While initially effective, cancers eventually reactivate the estrogen receptor even in the presence of these hormone therapies. My lab would like to identify novel downstream targets of the estrogen receptor that control proliferation as potential therapeutic targets for therapy relapsed disease. One potential target is GREB1, a gene whose expression is highly upregulated upon estrogen receptor activation. Previous studies have shown that GREB1 can regulate estrogen-dependent proliferation, yet the molecular mechanism behind this control is unknown. In the lab, we are actively investigating the molecular actions of the GREB1 protein.
Areas of Expertise
• Steroid hormone receptors
• Endocrine disrupting compounds
• Transcriptional regulation
• Chromatin and epigenetics