Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Rebecca Harris, MD, PhD, MA

Boston Children’s Hospital, Whitehead Institute
Pediatric Endocrinology


Healthy traits and diseases differ between women and men. The leading causes of disability and death in the United States – cancer, heart disease, and diabetes – demonstrate sex differences in prevalence, symptomatology, morbidity, and mortality. Sex hormones (estrogen and testosterone) and sex chromosomes (X and Y) mediate these differences through sex-biased gene expression, i.e. differences in gene expression between males and females. We hypothesize that sex hormones and sex chromosomes contribute to sex-biased gene expression through independent and interdependent mechanisms. To test this hypothesis we have initiated a large, longitudinal study of transgender or gender-diverse patients, patients with sex chromosome aneuploidies, differences/disorders in sex development, and healthy control subjects. We are isolating peripheral blood mononuclear cells (PBMCs) from each subject for bulk and single cell RNA-sequencing (scRNA-seq). Using the 10X Genomics platform, we analyzed expression of 19,443 genes from 110,776 cells from 25 individuals (n=6 transgender males, n=6 transgender females, n=6 cisgender (non-transgender) males, and n=7 cisgender females). We have developed a pipeline to standardize initial data processing and quality control which evaluates metrics including numbers of expressed genes, unique molecular identifiers, percent mitochondrial gene expression, and doublet scores. We filtered and integrated data and identified 14 distinct cell populations via dimensionality reduction using uniform manifold approximation and projection. Gene expression across samples for each sub-cellular population is highly correlated (r>0.92). We have identified the sex chromosome karyotype of individual cells using XIST expression to identify the X chromosome and a set of 11 widely-expressed Y chromosome genes to detect the presence of the Y chromosome. Using a pseudobulk approach, we have preliminarily identified 379 differentially expressed genes (23 X chromosome, 4 Y chromosome, and 352 autosomal genes); 96 of the genes are differentially regulated in more than one cell type. Analyses using pseudobulk and mixed effects modeling is ongoing.


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.