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.  For a number of reasons, 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).

Recent advances by the Page Lab provide an intellectual framework for studying these fundamental questions.  Through comprehensively sequencing sex chromosomes across multiple mammalian species, the Page Lab discovered that a group of genes on the sex chromosomes encode master transcriptional and epigenetic regulators, which control how cells turn genes on and off throughout the genome.  The fact that the X version is expressed in females and both the X and Y versions are expressed in males implies that gene activity across the genome is controlled differently in XX and XY cells.  The resulting female- and male-specific regulation of the genome likely affects all dimensions of human biology, including how disease susceptibility varies between males and females.  We are investigating this question on several fronts. We are studying individuals with sex chromosome aneuploidy at the clinical and molecular levels to understand the influence of sex chromosome dosage on phenotypes across the body and on genome-wide transcriptional regulation.  We are generating comprehensive catalogs of sex differences in gene expression across diverse tissues and cell types and multiple mammalian species, including model organisms important in pharmaceutical development.  We are investigating molecular and cellular sex differences in the heart, immune system, and brain — tissues that are especially relevant for diseases that demonstrate significant sex biases (heart disease, autoimmune disease, and autism). 
  

Bio

Page earned his undergraduate degree in chemistry at Swarthmore College in 1978. He trained in the laboratory of David Botstein at MIT, while earning an M.D. magna cum laude from Harvard Medical School and the Harvard-MIT Health Sciences and Technology Program. He is currently a Professor of Biology at MIT, and an Investigator at the Howard Hughes Medical Institute. In 1992, he founded the Whitehead Task Force on Genetics and Public Policy.  Page serves on the Selection Committees of the March of Dimes Prize in Developmental Biology and the Taubman Prize in Translational Medical Science. 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.  Page served as Director of the Whitehead Institute from 2004 to 2020.