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Haifan Lin, PhD

Eugene Higgins Professor of Cell Biology, and Professor of Genetics and of Obstetrics, Gynecology, and Reproductive Sciences; Director, Yale Stem Cell Center

Research Summary

We study molecular mechanisms underlying the self-renewing division of stem cells. Currently, we focus on small RNA-mediated epigenetic programming and translational regulation that are required for the self-renewal of germline and embryonic stem cells. Meanwhile, we are studying these mechanisms in cancer and gremlin development. Stem cells are characterized by their abilities to self-renew and to produce numerous differentiated daughter cells. These special properties enable stem cells to play a central role in generating and maintaining most tissues in higher organisms. Over-proliferation of stem cells can cause cancer, whereas under-proliferation of stem cells leads to tissue dystrophy, anemia, immuno-deficiency, or infertility. Drosophila and the mouse represent two powerful systems for studying stem cells since they allow easy access to combined genetic, cell biological, and molecular analyses. We use Drosophila as a pilot model to explore molecular mechanisms underlying stem cell division, and the mouse as an advanced model to expand what we learn from Drosophila to mammalian systems. Previously, we identified germline stem cells in the Drosophila ovary and revealed their self-renewing asymmetric division. We and others showed that the asymmetric division of these stem cells is controlled by both niche signaling and intracellular mechanisms. Using systematic genetic screens, we have identified key genes involved in both niche signaling and intracellular regulation of stem cell division. Among them, the piwi/argonaute gene family represent the only known gene family required for stem cell self-renewal in both animal and plant kingdoms. Currently, our research is focused on epigenetic programming and translational regulation of germline stem cell self-renewal mediated by the Piwi/Argonaute proteins and a novel class of non-coding small RNAs called piwi-Interacting RNAs (piRNAs) that we and others discovered in 2006. Meanwhile, we have been studying translational regulation of embryonic stem cells mediated by the Pumilio proteins.

Specialized Terms: Stem cell RNA-mediated epigenetic programming, post-transcriptional regulation


Research Interests

Cell Biology; Genetics; Gynecology; RNA Processing, Post-Transcriptional; Stem Cells; Embryonic Stem Cells; Argonaute Proteins

Selected Publications