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Amy Weinmann, Ph.D.
Amy Weinmann, Ph.D.
Associate Professor, Immunology
Dr. Weinmann received her PhD in Microbiology and Immunology from the University of California, Los Angeles in 2000. She completed a postdoctoral fellowship at the University of Wisconsin, Madison in 2003 and joined the University of Washington Department of Immunology faculty in November 2003.
Department of Immunology
University of Washington
Office E545, Box 358059
750 Republican Street
Seattle WA 98109-8059
Developmental gene expression profiles are precisely regulated by lineage-defining transcription factors that utilize both epigenetic and classical transactivation mechanisms to regulate their target genes. The T-box transcription factor family plays essential roles in numerous developmental systems, ranging from early embryogenesis into the adult. The dysregulation of the T-box family leads to several human genetic diseases, including immunodeficiencies, cancer, congenital heart defects, limb abnormalities, cleft palate, and pituitary deficiencies. In the immune system, two T-box factors, T-bet and Eomesodermin, have been shown to play critical roles in the development and functioning of both adaptive and innate immune cells. Genetic studies have shown that the loss of either T-bet, or a combination of T-bet and Eomesodermin, results in higher susceptibility to infectious diseases as well as alterations in the incidence for autoimmune conditions. In my laboratory, we study the mechanisms by which the T-box family establishes developmentally appropriate gene expression networks, with a special emphasis on understanding T-bet’s role in regulating gene networks in diverse immune cell types.
Our previous studies have demonstrated that T-box factors require both a family member specific transactivation potential and a conserved ability to recruit histone modifying activities to properly function at select target genes during cellular differentiation. Significantly, the T-box DNA binding domain, the defining feature for the T-box family, physically and functionally interacts with both H3K27-demethylase and H3K4-methyltransferase activities. These interactions are required for the ability of diverse T-box family members to establish gene networks in development, as noted by the numerous human genetic disease mutations specifically disrupting these activities. Current research in the lab is focused on understanding the context in which the T-box family utilizes the common epigenetic activities as well as the family member specific transactivation potential to regulate gene expression at both the global and individual target gene level. Importantly, examining these questions in T helper cell differentiation in the immune system provides a valuable model system to define the molecular requirements for establishing developmental gene networks.
1. Oestreich, K.J. and A.S. Weinamnn. Transcriptional mechanisms that regulate T helper 1 cell differentiation. Curr. Opin. Immunol. In Press, 2012.
2. Oestreich, K.J., S.E. Mohn, and A.S. Weinmann. Molecular mechanisms that control the expression and activity of Bcl-6 in Th1 cells to regulate flexibility with a Tfh-like gene profile. Nat. Immunol. 13: 405-411, 2012.
3. Oestreich, K.J. and A.S. Weinmann. Ikaros changes the face of NuRD remodeling. Nat. Immunol. 13: 16-18, 2012.
4. Oestreich, K.J. and A.S. Weinmann. T-bet employs diverse regulatory mechanisms to repress transcription. Trends Immunol. 33: 78-83, 2012.
5. Oestreich, K.J. and A.S. Weinmann. Encoding stability versus flexibility: Lessons learned from examining epigenetics in T helper cell differentiation. Curr. Top. Microbiol. Immunol. 356: 145-164, 2012.
6. Kao, C., K.J. Oestreich, M.A. Paley, A. Crawford, J.M. Angelosanto, M.A.A. Ali, A.M. Intlekofer, J.M. Boss, S.L. Reiner, A.S. Weinmann, E.J. Wherry. T-bet represses expression of PD-1 and sustains virus-specific CD8 T cell responses during chronic infection. Nat. Immunol. 12: 663-671, 2011.
7. Oestreich, K.J., A.C. Huang, and A.S. Weinmann. The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns. J. Exp. Med. 208: 1001-13, 2011.
8. Miller, S.A. and A.S. Weinmann. Molecular mechanisms by which T-bet regulates T-helper cell commitment. Immunol. Rev. 238: 223-46, 2010.
9. Miller, S.A., S. E, Mohn, and A.S. Weinmann. Jmjd3 and Utx play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression. Mol. Cell 40: 594-605, 2010.
10. Miller, S.A. and A.S. Weinmann. Common themes emerge in the transcriptional control of T helper and developmental cell fate decisions regulated by the T-box, GATA, and ROR families. Immunology 126: 306-315, 2009. PMCID: 2669811
11. Jenne, C.N., A. Enders, R. Rivera, S.R. Watson, A.J. Bankovich, J.P. Pereira, Y. Xu, C.M. Roots, J.N. Beilke, A. Banerjee, S.L. Reiner, S.A. Miller, A.S. Weinmann, C.C. Goodnow, L.L. Lanier, J.G. Cyster, J. Chun. T-bet dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow. J. Exp. Med. 206: 2469-81, 2009.
12. Miller, S.A. and A.S. Weinmann. An essential interaction between T-box proteins and histone-modifying enzymes. Epigenetics 4: 85-88, 2009.
13. Sekimata, M. M. Perez-Melgosa, S.A. Miller, A.S. Weinmann, J.A. Stamatoyannopoulos, C.B. Wilson. CTCF and T-bet orchestrate Th1 T cell-specific structure and function at the interferon-g locus. Immunity 31: 551-64, 2009.
14. Miller, S.A., A.C. Huang, M.M. Miazgowicz, M.M. Brassil, and A.S. Weinmann. Coordinated, but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression. Genes & Dev. 22: 2980-93, 2008. PMCID: 2577798
15. Lewis, M.D., S.A. Miller, M.M. Miazgowicz, K.M. Beima, and A.S. Weinmann. T-bet’s ability to regulate individual target genes requires the conserved T-box domain to recruit histone methyltransferase activity and a separate family member specific transactivation domain. Mol. Cell. Biol. 27: 8510-8521, 2007. PMCID: 2169399
16. Beima, K.M., M.M. Miazgowicz, M.D. Lewis, P.S. Yan, T.H-M. Huang, and A.S. Weinmann. T-bet binding to newly identified target gene promoters is cell-type independent, but results in variable functional effects. J. Biol. Chem. 281: 11992-12000, 2006
17. Weinmann, A.S. Novel ChIP-based strategies to uncover transcription factor target genes in the immune system. Nature Rev. Immunol. 4: 381-386, 2004.
B.A., Biology, University of Minnesota
Ph.D., Microbiology and Immunology, University of California, Los Angeles