David C. Page is the Director of the Whitehead Institute for Biomedical Research, Professor of Biology at MIT, and an Investigator of the Howard Hughes Medical Institute. A graduate of Swarthmore College, he earned his MD from Harvard Medical School and the Harvard-MIT Health Sciences and Technology program. He joined the Whitehead Institute, as the first Whitehead Fellow, in 1984.
Page’s laboratory explores fundamental differences between males and females in health and disease, both within and beyond the reproductive tract.
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.
The Page lab’s enduring interest in the foundations of sex differences stems from early studies of the human Y chromosome. Page’s lab first reported a DNA-based deletion map of the Y chromosome in 1986, a comprehensive clone-based physical map of the chromosome in 1992, and a systematic catalog of Y-linked genes in 1997. In 2003, his lab completed the sequencing of the human Y chromosome in conjunction with the Genome Institute at Washington University. These genomic studies led to unanticipated biological insights. The Page lab reconstructed the evolution of today’s X and Y chromosomes from an ancestral pair of chromosomes that existed 300 million years ago, and discovered molecular evolutionary mechanisms by which the Y chromosome became functionally specialized in spermatogenesis. The lab discovered and characterized the most common genetic cause of spermatogenic failure in humans: deletion of the AZFc region of the Y chromosome. The lab also found that aberrant crossing-over within the Y chromosome’s palindromes underlies a wide range of disorders of sexual differentiation, including Turner syndrome.
The lab’s expanded genomic studies of Y chromosomes in eight mammals revealed that male-specific, Y-chromosome genes are enriched for global regulators of cellular processes and gene regulation. These insights led the lab to a broader consideration of transcriptional differences between males and females throughout the body – differences that likely affect a range of phenotypes in healthy individuals, as well as the incidence, prevalence, and severity of a host of diseases. To investigate this possibility, the lab generated a comprehensive catalog of sex differences in gene expression across multiple tissues and cell types in five mammalian species, including important model organisms for drug development studies. This study yielded insight into the evolutionary dynamics of sex differences in gene expression and revealed how gene expression contributes to an upward shift in the distribution of height or body size in males relative to females.
Over the past three decades, the Page lab also led studies to understand the developmental regulation of germ cells and how they acquire a female or male identity (ultimately eggs or sperm). The lab used the mouse as an experimental model to genetically dissect the process of meiotic initiation, which is a critical juncture in mammalian development. One of the Page lab’s key findings overturned the long-held view that germ-cell sex determination is dependent on the timing of meiotic initiation. The lab also discovered and characterized an epigenetic mechanism that might explain the unique ability of germ cells to undergo dramatic specialization while retaining the potential to create a new, fully formed organism.