Professor of Pathology
Harvard Medical School
NRB-830
77 Avenue Louis Pasteur
Boston, MA 02115
PH: 617-432-1978
FX: 617-432-2789
dorf@hms.harvard.edu

Research Interests

Brain cells called astrocytes contribute to the inflammation of nervous tissue in multiple sclerosis and other neurodegenerative diseases. The pro-inflammatory activities of astrocytes are triggered when certain immune derived chemicals, called cytokines, bind to receptors on the astrocyte surface. The binding of one specific cytokine known as TNF has particularly dramatic effects on astrocytes.  Binding of this cytokine unleashes a torrent of proinflammatory mediators, especially the release of a class of chemical attractants, termed chemokines, which recruit inflammatory cells into the lesion. Reducing inflammation and chemokine synthesis may have significant therapeutic implications in chronic diseases of the central nervous system, cancer, and acute brain trauma.

Dr. Dorf’s laboratory uses several experimental approaches to identify the molecules that regulate chemokine responses to TNF. A large-scale RNAi screen identified phosphatase genes that regulated the NF-kB signaling pathway responsible for chemokine synthesis in brain-derived astrocytes. Of particular note, a PP2A holoenzyme was complexed to TRAF2. This was the first demonstration of a role for TRAF2 phosphorylation in the regulation of TNF or NF-kB dependent responses. The lab is analyzing the mechanisms of TRAF2 phosphorylation and the interactions of TRAF2 with downstream signaling molecules. Additional studies are aimed at understanding the mechanisms controlling nuclear localization of NF-kB.

Other projects in the lab involve cloning of lymphocytes capable of inducing an experimental multiple sclerosis-like disease and analysis of the cytokines produced by these cells.  

Publications

Xie, J. F. et al. Selective neutralization of the chemokine TCA3 reduces the increased injury of partial versus whole liver transplants induced by cold preservation. Transplantation 82, 1501-9 (2006).

Di, Y., S. Li, L. Wang, Y. Zhang, and M. E. Dorf. 2008. Homeostatic interactions between MEKK3 and TAK1 involved in NF-kB signaling. Cell Sig., in press.
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Abromson-Leeman, S., D. S. Ladell, R. T. Bronson, and M. E. Dorf. 2007. Heterogeneity of EAE mediated by multiple distinct T-effector subsets. J Neuroimmunol. 192:3-12.
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Li, S., Wang, L., Berman, M.A., Zhang, Y., and Dorf, 2006. M.E. RNAi screen in mouse astrocytes identifies phosphatases that regulate NF-kappaB signaling. Mol Cell 24, 497-509.
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