Esther A. Olaleye

Endocrine therapy is an effective and common treatment strategy for estrogen receptor (ER)-positive breast cancers. However, the development of endocrine resistance, through genetic mutations and epigenetic alterations, in about 40% of treated patients remains a significant therapeutic challenge. Liver X receptors (LXRs) are nuclear receptors that regulate lipid metabolism and cholesterol homeostasis and have been implicated in metabolic reprogramming in breast cancers and other malignancies. We previously identified a novel LXR ligand GAC0001E5 (1E5), with potent antiproliferative activity across breast cancer subtypes. Here, we investigate its mechanisms of action in responsive (MCF-7) and endocrine-resistant (MCF-7-TamR) ER-positive breast cancer cells. Treatment with 1E5 resulted in the downregulation of LXR and its target genes, and significantly reduced ERα expression and the expression of ER-responsive genes. Aberrant expression of androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2), both implicated in endocrine resistance, were downregulated following 1E5 treatment. siRNA-mediated knockdown of LXR expression only partially recapitulated the actions of 1E5, suggesting the involvement of LXR-dependent and independent mechanisms. Collectively, these findings reveal potential crosstalk between LXR and the genetic and epigenetic regulation of pathways involved in endocrine response and alternative signaling mechanisms, highlighting potential targets in endocrine-resistant breast cancer.

Maternal mortality and morbidity are critical health challenges in the U.S., and building the perinatal workforce is a key to providing high-quality maternal medical care and services. Texas Southern University (TSU), home to a Doctor of Pharmacy program, launched the first Maternal Health Education and Research Training (MHERT) program to educate a cohort of high school, pharmacy, and health sciences students. Aiming to raise awareness of maternal health issues, build research skills, and promote action-based solutions. MHERT integrated online self-paced interactive lessons with hands-on research or community projects. Topics included maternal health epidemiology, causes of morbidity and mortality, research methods, literature reviews, and the development of action plans addressing maternal health challenges. Assessment tools included quizzes, open-ended reflection responses, training surveys, and course evaluations. Running from 3 June to 26 July 2024, the program enrolled 22 students. All participants completed both course components. Course evaluations showed strong and consistent satisfaction with the program, with teaching effectiveness rated at 95% and 96% for mid-program and final evaluations, respectively. MHERT enhanced participants’ understanding of maternal health, improved research skills, and encouraged community engagement and interdisciplinary collaboration. It offers a scalable model to strengthen public health education among high school, pharmacy, and health sciences students.