Alexander Y. Rudensky, Ph.D.
Investigator, Howard Hughes Medical Institute and
Professor, Immunology

Department of Immunology
University of Washington
Office I 604 I HSC, Box 357370
1959 NE Pacific Street
Seattle, WA 98195-7650
Tel: 206.685-7644
Fax: 206.685-3612
Email: aruden@u.washington.edu

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HHMI Investigator Profile

Alexander Rudensky received his Ph.D. in Immunology in 1986 from the Gabrichevsky Institute for Epidemiology and Microbiology in Moscow. Prior to his faculty appointment to the University of Washington in 1992, he was a research fellow at the Institute of Genetics of Microorganisms in Moscow and Yale Medical School. He is an Investigator with the Howard Hughes Medical Institute.

Our research is focused on understanding the molecular mechanisms governing the development and function of CD4 T lymphocytes and their role in T cell mediated immunity and tolerance to self. Major areas of interest include: The molecular mechanisms governing the development and function of regulatory T cells and the role these cells play in the regulation of autoimmunity and immunity to infection. We are particularly interested in understanding the role of the forkhead family transcription factor Foxp3 in establishing and maintaining T cell tolerance. Transcriptional programs of T cell differentiation. Molecular mechanisms of regulation of autoimmunity and hyper-reactivity by immunosuppressive cytokines. The role of self-peptide:MHC class II complexes in the CD4 T cell development, including the role of these complexes in shaping the CD4 T cell TCR repertoire in developing thymocytes and the effects of self-peptide:MHC class II /TCR interactions in tuning the responses of these cells. In these studies, the laboratory employs a wide range of experimental techniques including traditional biochemical and molecular biological analysis; genetic approaches including conventional and conditional gene targeting, knock-in strategies, and conventional and inducible transgenesis; mass spectroscopy; bioinformatics; and classical immunological analysis utilizing both cellular in vitro techniques and whole animal experimentation

Students currently training in the Rudensky Lab: Lianne Hsing, Luke Williams, Steven Josefowitz

Selected Publications:

Rubtsov YP, Rudensky AY. (2007) TGF-beta signaling in control of T cell mediated self-reactivity. Nature Review Immunol. 7:443-453.

Zheng Y, Rudensky AY. (2007) Transcription factor Foxp3 in control of regulatory T cell lineage. Nature Immunol 8:457-462.

Kim J, Rasmussen J, Rudensky AY. (2007) Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nature Immunol 8:191-7.

Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY. (2007) Foxp3-dependent programme of regulatory T-cell differentiation. Nature, 445:77.

Williams LM, Rudensky AY. (2007) Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells required continued expression of Foxp3. Nature Immunol, 8:277-284.

Zheng Y, Josefowicz SZ, Kas A, Chu TT, Gavin MA, Rudensky AY. (2007) Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature, 445:936-940.

Rudensky AY, Gavin M, Zheng Y. (2006) FOXP3 and NFAT: partners in tolerance. 2006. Cell 126:375-87.

Hsieh CS, Zheng Y, Liang Y, Fontenot JD, Rudensky AY. (2006). An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nature Immunol 7:401-10.

Marie JC, Liggitt, D, Rudensky AY. (2006) Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity 25: 441-54

Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY. (2005) A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nature Immunol 6:1142-1151.

Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. (2005). Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity. 22:329-341.

Fontenot JD, Rudensky AY. (2005) "A well adapted regulatory contrivance": Regulatory T cell development and the forkhead family transcription factor Foxp3. Nature Immunol 6:331-337.

Kronenberg M, Rudensky AY. (2005) Regulation of self-tolerance and autoimmunity by self-reactive T cell lineages. Nature. 435:598-604.

Hsieh, C-S., Liang Y, Tyznik A., Liggitt D, Self S, AY Rudensky. (2004) Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity. 21:267-277.

Fontenot JD, Gavin MA, Rudensky AY. (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunol 4:330-336.

Gavin M, Clarke S, Negrou E, Gallegos A, Rudensky AY. (2002) Homeostasis and anergy in CD25+CD4+ regulatory T cells is maintained through multiple signal transduction pathways. Nature Immunol 3:33-41.

Honey K, Benlagha K, Beers C, Forbush K, Teyton L, Kleijmeer M, Rudensky, AY* (*corresponding author), Bendelac A. (2002) Thymocyte expression of cathepsin L is critical for NK T cell development. Nature Immunol 3:1069-74.

Barton G, Rudensky AY. (1999) Requirement for diverse, low abundance peptides in positive selection of T cells. Science 283:67-70.

Nakagawa TY, Brissette WH, Lira PD, Griffiths RJ, Petrushova N, Stock J, McNeish JD, Eastman SE, Howard ED, Clarke SRM, Rosloniec EF, Elliott EA, Rudensky AY. (1999) Impaired invariant chain degradation and antigen presentation, and diminished collagen-induced arthritis in cathepsin S null mice. Immunity 10:207-217.

Nakagawa T, Roth W, Wong P, Nelson A, Farr A, Deussing J, Villadangos JA, Ploegh H, Peters C, Rudensky AY. (1998) Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus. Science, 280:450-453.

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Updated September 2007