Nathan Mathewson
e-mail address: nmathew@umich.edu

Mentor: Pavan Reddy, MD

Research Description

Post translational protein modifications (PTM) are critical for the routine functions of cells. However, the role of an important PTM, neddylation, in regulating immune
responses, specifically those mediated by dendritic cells (DC) and T cells, which are critical for innate and adaptive immunity, is unknown. Upon stimulation, DCs and T cells release proinflammatory cytokines to elicit a variety of responses, however, the molecular processes regulating cytokine release are not well understood. Proinflammatory cytokines have a profound impact on initiating or exacerbating many disease states including chronic inflammatory diseases, septic shock, autoimmunity, and alloimmunity. In addition to cytokine release, T cells proliferate following stimulation resulting in increased immunity. The molecular processes regulating T cell immunity are also poorly understood.

Thus, we explore the role of neddylation in regulating DC and T cell functions utilizing functional and molecular techniques of in vitro investigation, as well as in vivo models of GVHD using allogeneic bone marrow transplantation.

Publications

Toubai T, Sun Y, Luker G, Liu J, Luker KE, Tawara I, Evers R, Liu C,
Mathewson N, Malter C, Nieves E, Choi S, Murphy KM, Reddy P. Host derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood. 2013.

Sun Y, Sun J, Tomomi T, Nieves E, Mathewson N, Tamaki H, Evers R, Reddy P.
PU.1-Dependent Transcriptional Regulation of miR-142 Contributes to Its
Hematopoietic Cell-Specific Expression and Modulation of IL-6. J Immunol.
2013.

Tawara I, Liu C, Tamaki H, Toubai T, Sun Y, Evers R, Nieves E, Mathewson N
Nunez G, Reddy P. Influence of donor microbiota on the severity of experimental graft-versus-host-disease. Biol. Blood Marrow Transplant.
2013;19(1):164–168.

Tawara I, Sun Y, Liu C, Tomomi T, Nieves E, Evers R, Alrubaie M, Mathewson N, Tamaki H, Reddy P.  Donor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease. J. Leukoc. Biol. (2012) doi:10.1189/jlb.1011510 PMID: 22262800

Abstracts

Nathan D. Mathewson, Tomomi Toubai, Yaping Sun, Hiroya Tamaki, Ying Wang, Katherine Oravecz-Wilson, Steven Kapeles, Guoqing Hou, Pavan Reddy.
A critical role for neddylation in regulating dendritic cell function. Oral and Poster
presentation. American Association of Immunologists, Honolulu, HI, 05/2013.

Awards

Monte V. Hobbs Student Award, June 2013

Rackham Conference Travel Grant, May 2013