The two subtypes of estrogen receptor, ERa and ERb, carry out non-overlapping functions inreproductive biology. ERb is capable of both interfering with ERa function and exerting its biological activityindependent of ERa. It remains unclear how the ERa-independent and ERa-competing functions of ERb areregulated. We recently made the pioneering discovery of an ERb-specific phosphotyrosine switch thatregulates ERb function in reproductive organs.

OverallSystems Analysis of Epigenomic Architecture in Cancer ProgressionDespite anti-hormone therapies in patients, the cognate receptors ER? and AR can remain functional tosupport oncogenic signaling for advanced progression of breast and prostate cancers. Intensive studies haveuncovered cellular and biochemical changes underlying the development of hormone resistance. However,epigenetic mechanisms for establishing and maintaining a hormone-resistant phenotype remain to beexplored.

Microtubule stabilizing agents (MSAs) are some of the most widely used and effective therapies availablefor the treatment of solid tumors. However, their utility is compromised by innate and acquired drugresistance. The taccalonolides (taccas) are a mechanistically unique class of MSAs that circumventmultiple clinically relevant forms of drug resistance. Multiple potent taccas identified by our laboratorieshave effective antitumor activity in drug sensitive and resistant in vivo models but suffer from a narrowtherapeutic window.

Advancing the Science of Cancer in LatinosProject Summary/AbstractThe proposed conference, ?Advancing the Science of Cancer in Latinos,? would occur February21-23, 2018, in San Antonio, Texas.

Self-renewing tumor-propagating cells drive continued tumor growth and are responsible for relapse. If the processby which tumor cells self-renew could be turned off, then tumors would regress and patients would remain relapsefree. The goal of this updated proposal is to define the cellular and molecular mechanisms by whichNotch regulates tumor-propagating potential and plasticity of the tumor propagating cell state inembryonal rhadomyosarcoma (ERMS), a devastating pediatric malignancy of the muscle.

This exploratory project is directed towards understanding the biological role of a novel oncogenic driver inEwing sarcoma. Ewing sarcoma is an aggressive cancer of bone and soft tissues in children with poor long-term outcome. It is characterized by the chromosomal translocation generating a fusion oncogene betweenEWS and an Ets family transcription factor, most commonly FLI-1. EWS-FLI-1 translocation accounts for 85%of Ewing sarcoma cases.