Amy Weinmann, Ph.D.
Assistant Professor, Immunology

Department of Immunology
University of Washington
Office: H-574B, Box 357650
1959 NE Pacific Street
Seattle, WA 98195-7650
Tel: 206.616-7235
Fax: 206.543-1013
Email: weinmann@u.washington.edu

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. Her laboratory is investigating mechanisms of transcriptional regulation in the immune system.

Transcription factors play a critical role in the development of the immune response and the deregulation of even a single factor can lead to disease states such as leukemia, autoimmunity, and allergic reactions. Part of how this occurs is that the selective loss of a factor can drastically alter the gene expression cascades responsible for the development of critical immune cell populations. Therefore, identifying the genes that are influenced by these factors will allow us to better address the molecular events that contribute to an appropriate immune response as well as those that are frequently deregulated in disease states. The transcription factor T-bet plays a significant role in the development of CD4+ T helper 1 (Th1) cells. Th1 cells secrete IFNg and are important in the development of the cell-mediated immune response to clear intracellular infections or pathogenically altered self-cells. A hyperactive Th1 response can contribute to autoimmune diseases such as Crohn's and type 1 diabetes. In addition to Th1 cells, T-bet is also expressed in multiple lineages in the immune system and is thought to influence cell-specific functions. In the absence of T-bet, cell-specific defects occur in Th1, natural killer, dendritic, and B cells. It is also worth noting that murine disease models for Crohn's, asthma, and lupus have all been established by altering T-bet levels. One of the goals of my research is to address the molecular mechanisms behind T-bet's role in the individual hematopoietic cell populations. One avenue of research to achieve this goal is to attain a better understanding of the genes that are directly regulated by T-bet in each cell type. What are the series of events that occur in response to the upregulation of T-bet activity? To address this question, newly developed target gene identification strategies will be employed to identify the genes that are directly bound by T-bet within the context of a given nuclear environment. Further analysis of individual T-bet target genes will also be undertaken to uncover transcriptional regulation mechanisms. These studies will provide one step in addressing the molecular series of events that occur in the developing cell-mediated immune response.

Students currently training in the Weinmann Lab: Sara Miller (MCB)

Recent Publications:

Beima, K.M., M.M. Miazgowicz, M.D. Lewis, P.S. Yan, T.H-M. Huang, and A.S. Weinmann. 2006. 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.

Mehta, D.S., A.L. Wurster, A.S. Weinmann, M.J. Grusby. 2005. NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression. Proc. Natl. Acad. Sci. U.S.A. 102: 2016-2021.

Weinmann, A.S. 2004. Novel ChIP-based strategies to uncover transcription factor target genes in the immune system. Nature Rev. Immunol. 4: 381-386. (pdf)

Townsend, M.J., A.S. Weinmann, J. Matsuda, R. Saloman, P.J. Farnham, C.A. Biron, L. Gapin, L.H. Glimcher. 2004. T-bet regulates the terminal maturation and homeostasis of NK and Va14i NKT cells. Immunity 20: 477-494.

Weinmann, A.S. and P.J. Farnham. 2002. Identification of unknown target genes of human transcription factors using chromatin immunoprecipitation. Methods 26: 37-47.

Weinmann, A.S., P.S. Yan, M.J. Oberley, T.H.-M. Huang, and P.J. Farnham. 2002. Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis. Genes & Dev. 16: 235-244.

Weinmann, A.S., S.M. Bartley, T. Zhang, M.Q. Zhang, and P.J. Farnham. 2001. Use of chromatin immunoprecipitation to clone novel E2F target promoters. Mol. Cell. Biol. 21: 6820-6832.

Weinmann, A.S., D.M. Mitchell, S. Sanjabi, M.N. Bradley, A. Hoffmann, H.-C. Liou, and S.T. Smale. 2001. Nucleosome remodeling at the IL-12 p40 promoter is a TLR-dependent, Rel-independent event. Nature Immunol. 2: 51-57.

Updated August 2006