- Ozbun, Michelle A Professor, The Maralyn S. Budke Endowed Professor of Viral Oncology
My laboratory studies the molecular mechanisms by which epigenetic factors, hormone signaling, and the tissue microenvironment regulate normal reproductive biology, and cancer progression. We are particularly interested in the role of the G protein-coupled estrogen receptor, GPER, in female reproductive tract physiology, metabolism, and the etiology of women’s cancers, including endometrial, ovarian, and breast cancer. We have also established collaborations with physicists and chemists, and together we are investigating the use of novel magnetic nanoparticles and imaging modalities to detect and treat cancer with high sensitivity and selectivity.
The goal of my research is to dissect the mechanisms by which cells respond to environmental cues, and how those interactions are altered during the progression from normal to neoplastic disease in women’s cancers. A major focus of my laboratory is the study of the novel G protein-coupled estrogen receptor, GPER (also known as GPR30). A multidisciplinary collaborative effort is the best approach to solve complex biological problems, and through a successful collaboration with Dr. Eric Prossnitz, we established several models crucial to dissect GPER function. Using animal models my group defined a role for GPER in epithelial cell proliferation. Concomitantly we made the seminal observation that GPER-selective agonists and antagonists modulate GPER activity in vivo, paving the way for preclinical evaluation of these compounds in disease models. Moreover we have demonstrated that GPER promotes breast tumor proliferation and metastasis using genetically modified animal models of breast cancer and explant cultures of human breast tissue. These observations led my laboratory to make the intriguing discovery that estrogen, acting through GPER, alters the orientation of the mitotic spindle, which we are exploring using complex 3-dimensional culture models. These results have important implications with respect to fundamental principles of cell division control and morphogenesis in estrogen-responsive tissues, and may lead to novel insights into the mechanisms by which estrogen promotes tumor progression. Another exciting area we are exploring relates to environmental estrogen mimics or xenoestrogens, chemicals in the environment and in foods that bind and activate estrogen receptors. The xenoestrogen bisphenol A (BPA) activates GPER along with the classical estrogen receptors, and we are exploring the consequences of BPA exposure during fetal life on breast development.
Based on my expertise in breast neoplastic progression, I established new collaborations with a multidisciplinary team, including physicists, chemists, and clinician researchers, focused on developing novel methods to detect, target, and treat breast cancers. Using animal models, we are developing multifunctional magnetic nanoparticles (mNPs) that can be targeted to specific tumors, followed by application of an alternating magnetic field to the targeted mNPs to deliver localized heat, or thermal therapy. I led the effort that culminated in our first breast cancer-focused manuscript, which was published in Breast Cancer Research in October 2011. The findings were also featured in a press release.