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Haifan Lin |
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Professor of Cell Biology, Director of Yale Stem Cell Center
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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 the self-renewal of germline and embryonic stem cells. Meanwhile, we are exploring the clinical implications of our findings.
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| Current Research: | |
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| 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.
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| 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 mediated by the Piwi/Argonaute proteins and a novel class of non-coding small RNAs called
p
iwi-
I
nteracting 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.
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| Representative Publications: | |
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Yin, H. and Lin, H. (2007) An Epigenetic Activation role of a PIWI-mediated RNAi Pathway in Drosophila. Nature 450, 304-308.
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| Brower-Toland, B*., Findley, S.*, Jiang, L., Liu, L., Dus, M., Zhou, P., Elgin, S., and Lin, H. (2007) Drosophila PIWI Associates with Chromatin and Interacts
Directly with HP1a. Genes & Development 21: 2300-2311 (Cover story; * co-first authors)
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| Wang, Z. and Lin, H. (2007) Sex-lethal is a Target of Bruno-mediated Translational Repression in Promoting the Differentiation of Stem Cell Progeny
during Drosophila Oogenesis. Dev. Biol. 302, 160-168.
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| Li Chen, L., Shen, R., Ye, Y., Pu, X., Liu, X., Duan, W., Wen, J., Wang, Y., Liu, Y., Lasky, L. C., Heerema,
N., Perrotti, D., Ozato, K., Kuramochi-Miyagawa, S., Nakano, T., Lin, H., Barsky, S., Gao, J-X. (2007)
Precancerous stem cells have the potential for both benign and malignant differentiation.
PLoS ONE
3, e293, 1-16.
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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).
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| 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. Grivna, S. T. *, Beyret, E. *, Wang, Z. and Lin, H. (2006) A novel class of small RNAs in mouse spermatogenic cells.
Genes & Development (Cover call-out paper, *co-first authors)
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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.
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| Contact Information: | |
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Professor of Cell Biology
Director of Yale Stem Cell Center
Phone: 203-785-6239(O)
Fax: 203-785-4305
E-mail: haifan.lin@yale.edu
Address
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
SHM I-213
333 Cedar Street
New Haven, CT 06520-8002
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