 |
 |
|
 |
||
 |
 |
|
 |
|
|
Last Updated: 2/26/2007
| Jonathan S. Serody, MD
Thomas Assoc Prof of Medicine and Immunology |  |
Research Interests
Our laboratory is interested in the mechanism by which T cells and antigen presenting cells migrate into tissues to mediate their function. We have focused on two areas that are important in cancer biology. Allogeneic stem cell transplantation is a common treatment for patients with refractory malignancies, however, the widespread use of this form of therapy is limited by the occurrence of graft-versus-host disease (GVHD). Our group was the first to show that chemokines are involved in the affector phase of GVHD (1). We followed this with a manuscript that demonstrated that T cells are the major source of CCL3 and that this chemokine had different effects on CD4+ and CD8+ T cells (2). Finally, we have recently found that the chemokine receptor, CCR5, when absent on T cells leads to accelerated GVHD due to increased activity of the CXCL10/CXCR3 axis and perhaps impaired migration of CCR5-expressing Treg cells (3,4).
Most recently, our group was the first to demonstrate that chemokine receptors are critical in the migration of regulatory T cells during GVHD and that the inability of these cells to migrate to specific organs enhanced organ-specific GVHD (5). Our assessment of the function of specific proteins in migration during GVHD was recently published as a review in Blood in 2005.
We have also focused on the migration of Treg cells and dendritic cells in tumor models. Our group was the first to show that the chemokine receptor, CCR5, had a pivotal role in the function of a dendritic cell vaccine in causing tumor regression in a melanoma animal model (6). This work has led to a collaboration with the pharmaceutical company, GSK, on the use of inhibitors of CCR5 in preclinical models prior to a possible phase I immunotherapy trial next year.
Additionally our group and our collabortors have been the first to in vivo imaging of eGFP transgenic T cells as a method to track their migration in GVHD and their interaction with tumor cells in GvL (7, 8).
Finally, we are enrolling patients on a trial designed to test the activity of vaccine therapy against HER-2/neu when combined with conventional therapy for patients with metastatic breast cancer.
Recent Accomplishments and Honors
2003--Scientific Session on Advances in GVHD at American Society of Hematology
2005: Member SPORE Parent Committee
2006 Elizabeth Thomas Chair of Medicine, Microbiology and Immunology
2007 Member TTT study section
Publications
1. Ng-Cashin J, Kuhns JJ, Burkett SE, Powderly JD, Craven RR, van Deventer HW, Kirby SL, Serody JS. Host absence of CCR5 potentiates dendritic cell vaccination. J Immunol.170:4201-4208, 2003.
2. Wysocki, CA, Burkett SB, Panoskaltsis-Mortari, A, Kirby SL, Luster AD, McKinnon K, Blazer BR, Serody JS. Differential roles for CCR5 expression on donor T cells during graft-versus-host disease based on pre-transplant conditioning. Journal of Immunology 172(2): 845-54, 2004.
3. Panoskaltsis-Mortari A, Price A, Hermanson JR, Taras E, Lees, C, Serody JS, Blazar BR. In Vivo Imaging of Graft-Versus-Host-Disease (GHVD) In Mice. Blood 103(9): 3590-8, 2004.
4. O'Shaughnessy MJ, Panoskaltsis-Mortair A, Hermansen, JR, Wagensteen OD, June C, Murphy WJ, Serody JS, Blazar BR. Dynamic imaging of T cell leukemia interactions. Cancer Research 64(11): 3914-21, 2004.
5. Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, Serody JS. Leukocyte migration and graft-versus-host disease. Blood 105(11): 4191-4199, 2005.
6. Wysocki CA, Jiang Q, Panoskaltsis-Mortair A, Taylor PA, McKinnon KP, Su L, Blazar BR, Serody JS. Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute GVHD. Blood 106(9): 3300-07, 2005.
7. Moran TP, Collier M, McKinnon KP, Davis NL, Johnston RE, Serody JS. A novel viral system for generating antigen-specific T cells. Journal of Immunology 175(5): 3431-3438, 2005.
8. van Deventer HW, O'Connor W, Jr Brickey WJ, Aris RM, Ting JP, Serody JS. C-C chemokine receptor 5 on stromal cells promotes pulmonary metastasis. Cancer Research 65(8): 3374-3379, 2005.
9. Taylor PA, Ehrhardt MJ, Roforth MM, Swedin JM, Panoskaltsis-Mortari A, Serody JS, Blazar BR. Preformed antibody, not primted T cells is the initial and major barrier to bone marrow engraftmetn in allosensitized recipients. Blood 109(3): 1307-1315, 2007.
10. Moran TP, Burgents JE, Long B, Ferrer I, Jaffee EM, Tisch RM, Johnston RE, Serody JS. Robust T and B cell response can induce tumor regression. (submited)
E-mail: serody@med.unc.edu
Telephone: (919) 966-6975
Address: Lineberger, CB# 7305 Chapel Hill, NC
