Department of Microbiology and Immunology
Chenthamarakshan Vasu, PhD
Director of Translational and Transplantation Immunology
Department of Surgery
Hollings Cancer Center, HO-612A
College of Medicine
Medical University of South Carolina
86 Jonathan Lucas St
Charleston, SC 29425
1997-1999 Postdoctoral Fellow, University Malaya
1999-2002 Postdoctoral Fellow, University of Illinois at Chicago
2002-2004 Research Assistant Professor, University of Illinois at Chicago
2004-2011 Assistant Professor, University of Illinois at Chicago
PhD in Biochemistry/Immunology: Nagpur University, India
Research interests of Dr. Vasu’s Lab include: 1) understanding the immune tolerance mechanism, 2) developing novel strategies to treat autoimmunity and transplant rejection, and 3) designing novel dendritic cell based therapeutic approaches for tumors.
Co-stimulation and co-repression in immune tolerance: Co-stimulatory and co-repressor pathways are considered essential for T cell activation, differentiation, and regulation of immune response. Dr. Vasu’s Lab, therefore, believes that a thorough understanding of the role of these signaling pathways in T cell function is very important for developing intervention strategies against immune mediated disorders. Primary focus of this project is on understanding the role of signaling through CD28, CTLA-4, PD-1 and BTLA in maintaining peripheral tolerance. These studies can lead to development of effective targeted immunotherapy approaches for autoimmunity and transplant rejection.
Innate immune receptors on mucosal immune tolerance: Immune cells in the intestinal mucosa provide first line of defense against microbial invasion. However, these cells are continuously exposed to microbial and food components, and if the immune response is not held in check, then the development of an exaggerated immune response could lead to chronic inflammatory disorders. One of the recently initiated projects in Dr. Vasu’s Lab is focused on understanding the role of innate immune receptors such as TLR2 and dectin 1 in promoting tolerogenic immune response and/or preventing inflammation. Studies are focused on understanding the differences in the innate immune responses between intestinal immune cells and their peripheral counterparts when these receptors are engaged. The ultimate goal of this study is to appropriately and safely manipulate the immune response of intestinal mucosa using dietary approaches for treating autoimmunity.
Approaches to treat autoimmunity and Transplant rejection: Traditional therapeutic approaches for autoimmune diseases and transplant rejection have relied upon administration of immunosuppressive agents which results in global, non-specific attenuation of the immune response with side effects and variable therapeutic outcomes. Dr. Vasu’s Lab is also focused on developing and testing novel antigen specific targeted immune tolerance strategies for these clinical conditions. In one approach dendritic cells are engineered to manipulate signaling at the immune synapse during antigen presentation. The other strategy involves use of microsphere based artificial antigen presenting system for targeted deletion of pathogenic T cells, and induction and expansion of antigen specific Tregs with the ability to suppress autoimmunity and transplant rejection.
Tumor immunotherapy: In spite of the antigen specificity of considerable number of tumor-infiltrating lymphocytes (TILs) and T cells in the peripheral blood and tumor microenvironment, these cells are not capable of clearing tumors due to their immunosuppressive or tolerant nature. Dr. Vasu’s Lab is developing novel engineered dendritic cell based strategies not only to generate a strong anti-tumor effector T cell response, but also to convert existing tumor specific suppressor/regulatory T cells into IL-17 producing effector T cells in vivo for effectively eliminating cancer cells. This strategy exploits the suppressive environment of tumors for converting tolerant T cells to tumor antigen specific effector T cells.
Recent Publications | Additional Publications
Ganesh BB, P Bhattacharya, A Gopisetty, JR Sheng, C Vasu, and BS Prabhakar. (2011) IL-1beta promotes TGF-beta1 and IL-2 dependent Foxp3 expression in regulatory T cells. PLoS One 6(7):e21949.
Karumuthil-Melethil S, N Perez, R Li, BS Prabhakar, MJ Holterman, and C Vasu. (2010) Dendritic cell directed CTLA-4 engagement during pancreatic beta-cell antigen presentation delays type 1 diabetes. J Immunol 184:6695-708.
Ganesh BB, D Cheatem, JR Sheng, C Vasu, and BS Prabhakar. (2009) GM-CSF induced CD11c+CD8a- DCs suppress autoimmune thyroiditis through the induction of Foxp3+ and IL-10+ T regulatory Cells. Int Immunol 21(3):269-82.
Cheatem D, BB Ganesh, E Gangi, C Vasu, and BS Prabhakar. (2009) Modulation of Dendritic Cells Using Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Delays type 1 diabetes by Enhancing CD4+CD25+ Regulatory T Cell Function. Clin Immunol 131(2):260-70.
Karumuthil-Vellasamy KM, C Vasu, SD Puthucheary, and J Vadivelu. (2009) Comparative analysis of extracellular enzymes and virulence exhibited by Burkholderia pseudomallei from different sources. Microb Pathog 47(3):111-7.
Perez N, S Karumuthil-Melethil, R Li, BS Prabhakar, MJ Holterman, and C Vasu. (2008) Preferential costimulation by CD80 results in IL-10 dependent TGF-beta1+ adaptive regulatory T cell generation. J Immunol 180(10):6566-76.
Sonal G, S Manicassamy, C Vasu, A Kumar, W Shang, and Z Sun. (2008) Differential Requirement of PKC-theta for the development and function of natural regulatory T cells, Mol Immunol 46(2):213-24.
Karumuthil-Melethil S, N Perez, R Li, and C Vasu. (2008) Induction of Innate Immune Response through Toll-like Receptor 2 and Dectin 1 prevents type 1 diabetes. J Immunol 181(12):8323-34.
Ruobing Li, N Perez, S Karumuthil-Melethil, and C Vasu. (2007) Bone Marrow is a Preferential Homing site for Autoreactive T cells in type 1 diabetes. Diabetes 56:2251-2259.
Galbiati F, V Basso, L Cantuti, MI Givogri, A Lopez-Rosas, N Perez, C Vasu, H Cao, R van Breemen, A Mondino, and E Bongarzone. (2007) Autonomic denervation of lymphoid organs leads to epigenetic immune atrophy in a mouse model of Krabbe disease. J Neurosci 27(50):13730-8.
Ruobing Li, N Perez, S Karumuthil-Melethil, BS Prabhakar, MJ Holterman, and C Vasu. (2007) Enhanced engagement of CTLA-4 induces antigen specific CD4+CD25+Foxp3+ and CD4+CD25-TGF-beta1+ adaptive regulatory T cells: J Immunol 15; 179(8):5191-5203.
Title: Dendritic cell directed T cell negative regulation for treating autoimmunity
Funding Period: 02/2009 – 01/2014
Title: Antigen specific therapy for lupus
Agency: Lupus Research Institute
Funding Period: 02/2011 – 01/2014