Haifan Lin, Ph.D.

Professor of Cell Biology Director, Yale Stem Cell Center
Phone: (203) 785-6239 (O) Lab: (203) 785-6215 Fax: (203) 785-4305 e-mail: haifan.lin@yale.edu		Department of Cell Biology Yale University School of Medicine 333 Cedar Street PO Box 208002 New Haven, CT 06520-8002 <Courier Address> Yale Stem Cell Center Yale University School of Medicine 10 Amistad Street, Room 237 PO Box 208073 New Haven, CT 06520-8002

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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 stem cell self-renewal in the germline.  Meanwhile, we are exploring the clinical implications of our findings.  

Stem cells are characterized by their abilities to self-renew and to produce numerous differentiated daughter cells. These two 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 and human 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, piwi/argonaute genes represent the only known family of genes 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 as mediated by the Piwi/Argonaute proteins and a novel class of non-coding small RNAs called piwi-Interacting RNAs (piRNAs) that we and others recently discovered.  Meanwhile, we have begun to explore the role of these mechanisms in human embryonic stem cell division and oncogenesis.

Publications in 2006

Grivna, S. T. *, Beyret, E. *, Wang, Z. and Lin, H. (2006) A novel class of small RNAs in mouse spermatogenic cells.  Genes & Development (Advanced online publication: June 9, 2006, 10.1101/gad.1434406. *co-first authors)

Grivna, S. T., Pyhtila, B. and Lin, H. (2006) MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis.  Proc. Natl. Acad. Sci. 103, 13415-13420. Early online: 10.1073/pnas.0605506103.

Megosh, H.*, Cox*, D. N., Chris Campbell, C. and Haifan Lin, H. (2006) The Role of PIWI and the miRNA machinery in Drosophila germline determination. Current Biology. 16, 1884–1894 (*co-first authors). Early Online: doi:10.1016/j.cub.2006.08.051.

Wang, Z. and Lin, H. (2006) Sex-lethal is a Target of Bruno-mediated Translational Repression in Promoting the Differentiation of Stem Cell Progeny during Drosophila Oogenesis. Dev. Biol. Early Online: (http://dx.doi.org/10.1016/j.ydbio.2006.09.016).

Noora Kotaja, N., Lin, H.,  Martti Parvinen, M., and Sassone-Corsi, P.  (2006) Interaction of PIWI/Argonaute family member MIWI and microtubule-binding motor protein KIF17b in chromatoid bodies of male germ cells.  J. Cell Sci. 119, 2819-2825.

Lin, H. (2007)  piRNA in the germline.  Science, 316, 397.