Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Carrie Mahoney, PhD

Beth Israel Deaconess Medical Center/Harvard Medical School


Background. Women experience numerous physiological changes through their perimenopausal and menopausal transition, including severe sleep disturbances, mood changes and hot flashes. Hypothalamic neurons that express the wake-promoting orexin neuropeptides may be a key site through which low estradiol mediates these challenging symptoms. The orexin neurons coordinate many responses to stress from behavioral to physiological. Furthermore, expression of the orexin peptides appears to be regulated by estradiol as after ovariectomy; expression of prepro-orexin mRNA is increased and replacement with estradiol decreases expression. Does this change in orexin expression contribute to the physiological and behavioral symptoms seen with chronically low estradiol? Do the changes in estradiol with menopause result in different responses to stress and influence cognitive flexibility or risk of mood disorders? Objectives. We hypothesize that low estradiol increases orexin signaling, resulting in less sleep and heightened responses to stress. Methods. We will use histological, chemogenetic and behavioral assays to determine expression levels of orexins, sleep responses to stress, and the role orexins have in hot flashes as measured by FLIR imaging and in regulating the stress response in ovariectomized mice. Conclusion. Collectively, these multidisciplinary experiments will improve our understanding of how the orexin system contributes to the poor sleep and heightened stress responses that occur with chronic low estradiol in a mouse model of menopause. From a translational perspective, these experiments will help guide the potential treatment of the symptoms of menopause using orexin agonists and antagonists.


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.