Valeria Sanabria Guillen

Research Description: The estrogen receptor (ER), a hormone-activated transcription factor, plays a critical role in the development and prognosis of breast cancer. Despite the emergence and widespread use of drugs that target ER, a profound need remains for next-generation estrogen receptor ligands that show improved therapeutic outcome and reduced side effects while fending off resistance. Our work focuses on the development of estrogen receptor modulators and degraders as potential therapeutics for breast cancer, with a focus on improving potency, oral bioavailability, and effectiveness in mutant and treatment-resistant in vitro and in vivo models.  As part of this process, we seek to elucidate differential molecular mechanisms that are mediated by the structure-activity relationship of different ligands with ER, assessing their impacts on hormone-dependent gene transcription, signal transduction pathways, regulation of cell proliferation, and epigenetic regulation of ER-dependent genes.