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Member Information
Steve Reiner, MD
Professor of Medicine, Department of Infectious Diseases
Office Phone:
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Website(s): http://www.uphs.upenn.edu/abramson/reiner.html;
Education:
Keywords: Immunology and immunity to infectious organisms.
Research and/or Clinical Interests:
The Reiner laboratory studies gene transcription during cellular differentiation using lymphocytes as a model system. We are particularly interested in the epigenetic regulation of gene silencing and activation.
Summary:
The quality of the helper T cell response against antigen can determine the outcomes of infectious, inflammatory, and autoimmune diseases. Mature Th1 and Th2 cell subsets are thought to arise from a common naive progenitor. In these precursor cells, effector cytokine genes appear to exist in a restrictive structure, which is determined by methylation of cytosine bases and higher-order structure of chromatin. The restrictive gene structures appear to be plastic, giving way to more active structures in some daughter cells. Some genetic loci, which are active in naive cells, however, become silenced during terminal differentiation. Both the derepression of silent loci and the silencing of active loci appear to be linked to the process of DNA replication. Future investigation will be directed toward understanding the way in which patterns of gene expression are altered or transmitted during the cell division of helper T lymphocytes.
Representative Publications:
Hutchins, A.S., Mullen, A.C., Lee, H.W., Sykes, K.J., High, F.A., Hendrich B.D., Bird, A.P. and Reiner, S.L. Gene silencing quantitatively controls the function of a developmental trans -activator. Molecular Cell, 10:81-91, 2002.
Mullen, A.C., Hutchins, A.S., High, F.A., Lee, H.W., Sykes, K.J., Chodosh, L.A. and Reiner, S.L. Hlx is induced by and genetically interacts with T-bet to promote heritable T H 1 gene induction. Nature Immunology, 3:652-658, 2002.
Mullen, A.C., Hutchins, A.S., Villarino, A.V., Lee, H.W., High, F.A., Cereb, N., Yang, S.Y., Hua X. and Reiner, S.L. Cell Cycle Controlling the Silencing and Functioning of Mammalian Activators. Current Biology, 11:1695-1699, 2001.
Doyle, A.M., Mullen, A.C., Villarino, A.V., Hutchins, A.S., High, F.A., Lee, H.W., Thompson, C.B. and Reiner, S.L. Induction of CTLA-4 restricts clonal expansion of helper T cells. Journal of Experimental Medicine, 194: 893-902, 2001.
Mullen, A.C., High, F.A., Hutchins, A.S., Lee, H.W., Villarino, A.V., Livingston, D.M., Kung, A.L., Cereb, N., Yao ,T-P., Yang, S.Y. and Reiner, S.L. Role of T-bet in Commitment of T H 1 cells before IL-12-dependent selection. Science, 292:1907-1910, 2001.
