Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Sudeshna Fisch, PhD

Brigham and Women’s Hospital


Pulmonary arterial hypertension (PAH) is a fatal and highly heterogenous disorder characterized by progressive changes in vascular remodeling that, left unchecked, can lead to obstruction of pulmonary arteries. Chronic obstruction in lung vasculature can cause sustained, elevated pulmonary arterial pressure, ultimately leading to right ventricular (RV) hypertrophy and failure. It is known that males present with more severe symptoms upon diagnosis, but epidemiologic reports point to a higher incidence of PAH in females. It is plausible that female sex hormones, primarily estrogen, regulate the development of PAH in women, but the actual mechanics of this linkage remain unknown. A possible causative link could be dysregulated bone morphogenetic protein receptor 2 (BMPR2) signaling. BMPR2 can be reduced by overexpressing BMPR2 modifier genes, leading to low BMPR2 levels which, if below a critical threshold, can trigger PAH. Several microRNAs are known to regulate BMPR2. In vitro, estradiol treatment of pulmonary artery endothelial cells (PAECs) and lymphocytes prompts the estrogen receptor to target a binding site in the BMPR2 gene promoter inhibiting its transcription, but a confounding variable is estrogen’s ability to attenuate the effects of certain microRNAs- including miR-21-to contribute to BMPR2 downregulation. We will investigate the role of miR-21 and any other microRNAs that are expressed in PAH animal hearts in the context of sex-specific BMPR2 signaling pathway assessment. We will do this using a rat model of PAH secondary to pulmonary arterial constriction (PAC). We and others have shown that miR-21, a short non-coding RNA, is expressed in the heart and connected to RV remodeling following pulmonary arterial pressure overload. We will perform a microRNA- based CRISPR screen using male and female-specific rat hearts exhibiting RV hypertrophy to understand what downstream genes are modified that can also be linked to the pathobiology of pulmonary arterial hypertension (PAH).


3PM – Welcome Remarks
3:05PM – Keynote Address
3:45PM – Featured Short Talks
4:20PM – Lightning Talks
4:50PM – Closing Remarks

Keynote Speaker

Janine Austin Clayton, MD

Janine Austin Clayton, M.D., Associate Director for Research on Women’s Health and Director of the Office of Research on Women’s Health (ORWH) at the National Institutes of Health (NIH), is the architect of the NIH policy requiring scientists to consider sex as a biological variable across the research spectrum. This policy is part of NIH’s initiative to enhance reproducibility through rigor and transparency. As co-chair of the NIH Working Group on Women in Biomedical Careers with NIH Director Dr. Francis Collins, Dr. Clayton also leads NIH’s efforts to advance women in science careers.

Prior to joining the ORWH, Dr. Clayton was the Deputy Clinical Director of the National Eye Institute (NEI) for seven years. A board-certified ophthalmologist, Dr. Clayton’s research interests include autoimmune ocular diseases and the role of sex and gender in health and disease. She is the author of more than 120 scientific publications, journal articles, and book chapters.
Dr. Clayton, a native Washingtonian, received her undergraduate degree with honors from Johns Hopkins University and her medical degree from Howard University College of Medicine. She completed a residency in ophthalmology at the Medical College of Virginia. Dr. Clayton completed fellowship training in cornea and external disease at the Wilmer Eye Institute at Johns Hopkins Hospital and in uveitis and ocular immunology at NEI.

Dr. Clayton has received numerous awards, including the Senior Achievement Award from the Board of Trustees of the American Academy of Ophthalmology in 2008 and the European Uveitis Patient Interest Association Clinical Uveitis Research Award in 2010. She was selected as a 2010 Silver Fellow by the Association for Research in Vision and Ophthalmology. In 2015, she was awarded the American Medical Women’s Association Lila A. Wallis Women’s Health Award and the Wenger Award for Excellence in Public Service. Dr. Clayton was granted the Bernadine Healy Award for Visionary Leadership in Women’s Health in 2016. She was also selected as an honoree for the Woman’s Day Red Dress Awards and the American Medical Association’s Dr. Nathan Davis Awards for Outstanding Government Service in 2017.