Immunology
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Michael J. Grusby

Department of Immunology and Infectious Diseases
Harvard School of Public Health
FXB Building, Room 205
651 Huntington Avenue
Boston, MA 02115
Tel: 617-432-1240
Fax: 617-432-0084
e-mail:mgrusby@hsph.harvard.edu
4 Postdoctoral Fellows, 1 Graduate Student

 Michael Grusby

One focus of my laboratory is on the role of the signal transducer and activator of transcription (STAT) family of transcription factors in the differentiation and function of T helper (Th) cells. Previously, we have shown that STAT6-deficient mice have impaired IL-4-induced responses, including the generation of Th2 cells. Similarly, STAT4-deficient mice are unable to differentiate Th1 cells in response to IL-12. We are presently creating novel transgenic and gene-targeted mice with which we can temporally and spatially modulate STAT4 and STAT6 expression to further understand the role of these signaling molecules in differentiated Th cell responses. A second interest in the laboratory is in understanding how STAT signaling is regulated. Recently, we have used novel yeast two-hybrid approaches to identify STAT-interacting proteins. One such molecule (SLIM) is a novel PDZ-LIM containing protein that acts as an ubiquitin E3 ligase. A second STAT-interacting molecule we have identified appears to be a protein tyrosine phosphatase, and we are currently investigating the role of these molecules in STAT signaling. Finally, the laboratory is also interested in the recently described cytokine IL-21. We have shown that IL-21 is preferentially expressed by Th2 cells, and that exposure of naive Th cell precursors to IL-21 specifically inhibits the subsequent production of IFN-g by developing Th1 cells. We are presently working on understanding the mechanistic basis of these observations, as well as investigating the role of IL-21 in autoimmune diseases.

 

Papers & Publications:

  1. Wurster, A.L., Rodgers, V.L., Satoskar, A.R., Whitters, M.J., Young, D.A., Collins, M. and Grusby, M.J. 2002. IL-21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon g-producing Th1 cells. J. Exp. Med. 196:969-977.
  2. Metha, D.S., Wurster, A.L. Weinmann, A.S. and Grusby, M.J. 2005. NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression. Proc. Natl. Acad. Sci. USA. 102:2016-2021.
  3. Tanaka, T., Soriano, M.A. and Grusby, M.J. 2005. SLIM is a nuclear ubiquitin E3 ligase that negatively regulates STAT signaling. Immunity. 22:729-736.