Division of Reproductive Biology Research

Xu Laboratory

Email: e-xu@northwestern.edu
Telephone: (312) 503-0842
Fax: (312) 908-5603

Our group takes a combined genetic, evolutionary and developmental biology approach towards our mission in understanding mechanisms of common diseases affecting women's health. We reason that most diseases including women-specific diseases arose from problems at cellular levels in one or several specific reproductive organs. Understanding fundamental machinery regulating cell proliferation, determination and differentiation during human reproduction not only could improve our understanding of pathogenesis of reproductive diseases but also could reveal novel biomarkers for diagnostics as well as novel targets for therapeutics of women reproductive diseases.
Reproduction is widespread throughout most animals from sponges, insect, to mammals including human. Our recent research has uncovered evidence for ancient history of human reproductive regulatory machinery. Specifically we have found that human Deleted in AZoospermia (DAZ) family evolved from an ancient reproductive gene, originating at the dawn of animal evolution. The founding member of DAZ family--BOULE homologs are present throughout almost all animals and share conserved reproductive-specific requirement in distant lineages, supporting a common origin of animal sperm-making. We have also revealed a novel requirement of human DAZ family proteins and established animal models in both mouse and flies to study how those conserved RNA binding proteins contribute to germ cell development in humans.
Another common developmental process during animal reproduction is stem cell development. We have focused on highly conserved homologs of germ line stem cell factors—Pumilio in mice and investigated their function in mammalian germ cell development as well as other reproductive tissues. We have found that mammalian PUM proteins not only have conserved germ cell function but also play important roles in many other somatic tissues. We hypothesize that PUM is a key posttranscriptional regulator that control gene expression in many different tissues. Deregulation of PUM and its pathway could contribute to reproductive diseases including gynecological cancers and infertility. We are focusing on understanding the function and components of PUM-mediated posttranscriptional pathways during development and human diseases.

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