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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.



Toubai T, Hou G, Mathewson N, Liu C, Wang Y, Oravecz-Wilson K, Cummings E, Rossi C, Evers R, Sun Y, Wu J, Choi SW, Fang D, Zheng P, Liu Y, Reddy P. Siglec-G-CD24 axis controls the severity of graft-versus-host disease in mice. Blood. 2014; 123, 3512–3523.

Toubai T, Mathewson N, Reddy P. The role of dendritic cells in graft-versus-tumor effect. Front. Immunol. 2014; 5(1):66.

Mathewson N, Toubai T, Kapeles S, Sun Y, Oravecz-Wilson K, Tamaki H, Wang Y, Hou G, Sun Y, Reddy P. Neddylation plays an important role in the regulation of murine and human dendritic cell function. Blood. 2013 Sep 19;122(12):2062-73. doi: 10.1182/blood-2013-02-486373. Epub 2013 Jul 17.

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


Nathan Mathewson, Tomomi Toubai, Yaping Sun, Julia Wu, Katherine Oravecz-Wilson, Ying Wang, Guoqing Hou, Pavan Reddy. Neddylation regulates T cell responses. American Association of Immunologists, Pittsburg, PA. May 2014. Oral and Poster Presentation

Nathan Mathewson, Anna Mathew, Katherine Oravecz-Wilson, Julia Wu, Tomomi Toubai, Emily Cummings, Subramaniam Pennathur, Pavan Reddy. Microbial metabolites modulate GI mucosal damage from graft versus host disease (GHVD). American Association of Immunologists, Pittsburg, PA.
May 2014. Poster Presentation

Nathan Mathewson, Tomomi Toubai, Yaping Sun, Ying Wang, Katherine Oravecz-Wilson, Guoqing Hou, Julia Wu, Pavan Reddy. Targeting SAG in Donor T Cells as a Novel Strategy for Reducing GVHD. American Society for Blood and Marrow Transplantation, Grapevine, TX. March 2014. Oral Presentation

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.


American Association of Immunologists (AAI), Life Technologies Trainee Achievement Award, March 2014

American Association of Immunologists (AAI), Trainee Abstract Award, February 2014

Rackham Conference Travel Grant, University of Michigan, 2014

Monte V. Hobbs Student Award, June 2013

Rackham Conference Travel Grant, University of Michigan, 2013

Rackham Conference Travel Grant, February 2013

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