David C. Page

Question

What are the differences and similarities between males and females throughout the body at the molecular level, and how do they affect health and disease?

Approach

David Page’s research career has focused on understanding where male and female cells, tissues, and organs are essentially the same and where they are fundamentally different.  Many debilitating diseases, including heart failure, systemic lupus, autism spectrum disorder, and many cancers, show striking yet unexplained sex biases in prevalence and severity.  Such biases have historically been attributed entirely to cell-extrinsic factors, such as sex hormones or environment.  The medical and biomedical research community have long ignored the multifaceted function and impact of the X and Y chromosomes (the sex chromosomes).  The resulting blind spot means that biomedicine has little knowledge of the regulatory capacities and specific effects of sex chromosomes, or of the potentially widespread molecular differences—and health implications—that result from being male (XY) or female (XX).

The Page Lab is now making significant progress towards this goal, having developed a model for how the X and Y influence biological sex differences across the body.  This model, rooted in their intensive studies of the sex chromosomes over the past three decades, was recently accelerated though the establishment of a research platform harnessing the natural variation in X and Y copy number found in humans.  This platform enables the lab to differentiate the two states of the X chromosome: the active X (Xa), which is present in both males and females, and the so-called inactive X (Xi), which is female-specific.  The Page lab discovered that, despite its name, Xi plays a substantial role in influencing gene expression across the genome and across the body.  Their model offers a new view of the human X chromosome: Genes expressed from Xi (and their counterparts on the Y) have widespread regulatory effects that likely underlie all biologically based sex differences.  Understanding these fundamental, global, and cell-autonomous sex differences is key to understanding health differences in women and men. 
  

Bio

In 1979, David Page became the first student anywhere in the world to work on what would become the Human Genome Project. He joined the Whitehead Institute for Biomedical Research at its opening in 1984, as the first Whitehead Fellow, and has been a member of its faculty since 1988. He served as Whitehead’s fourth and longest serving Director and President, from 2004 to 2020. Page is also a Professor of Biology at MIT and an Investigator of the Howard Hughes Medical Institute. A graduate of Swarthmore College, Page earned his MD from Harvard Medical School and the Harvard-MIT Health Sciences and Technology program.

Page’s honors include a MacArthur Prize Fellowship, Science magazine’s Top Ten Scientific Advances of the Year (1992 and 2003), the Francis Amory Prize of the American Academy of Arts and Sciences, and the March of Dimes Prize in Developmental Biology. He is a Member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences.

He serves as Chair of the Visiting Committee of Harvard Medical School/Harvard School of Dental Medicine and on the Board of Directors of PepsiCo.