A possible explanation for these tissue-dependent effects is the existence of more than one estrogen signaling pathway. In addition to the classic estrogen pathway involving the regulation of gene transcription by the estrogen receptor (ER), there are multiple estrogen receptors, including ER alpha, ER beta and the G-protein coupled receptor GPR30 that can signal from different parts of the cell such as the nucleus, cytoplasm, mitochondria and plasma membrane. A number of these other pathways involve crosstalk with other signal transduction proteins, so it is possible that different effects seen in different tissues arise from certain pathways dominating in certain tissues.


Our lab uses chemical techniques to try to probe these different pathways in specific subcellular locations using bioactive conjugates. For more detailed information click on the link below.

Untangling the Estrogen Receptor Web

Drugs targeting estrogen action are used in the treatment of breast cancer and in the treatment of menopausal systems such as osteoporosis and hot flashes. The major problem with these therapies is that the effects of the drug are not limited to the target tissue. The common breast cancer hormone therapy tamoxifen, is anti-estrogenic in the breast but is pro-estrogenic in the uterus, leading to increased risk of uterine cancer. Another estrogen targeted drug, raloxifene, has a different tissue response profile. Our lab wants to know why these drugs have different responses in different tissues and then synthesize new drugs with better profiles for breast cancer and hormone replacement therapies. We hope that our work will lead to better treatments for breast cancer with less side effects, more effective treatments for antiestrogen-resistant breast cancer and perhaps improved therapies for menopausal symptoms

Interested in working on this research? Click here.