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Immune Tolerance Research Lab
Director: Chenthamarakshan Vasu, PhD
College of Medicine Research Building (COMRB)
Room #7100 (Lab)/#7113 (Office)
Phone: 312-996-1121 (Lab)
312-996-2431 (Office)

Dr. Vasu is an Assistant Professor in the department of Surgery. He obtained his pre- and post-doctoral training from prominent research institutions in India and Malaysia before joining the University of Illinois at Chicago. He obtained additional post-doctoral training at UIC before joining the department of Surgery as an Assistant Professor in 2004. He has more than 20 years of experience in Clinical and Basic Immunology research. His research expertise includes basic T cell and dendritic cell biology, immune pathogenesis of autoimmune diseases, and parasitic and bacterial infection, development of vaccines and diagnostics for various clinical conditions, targeted therapies for autoimmune diseases. His research Lab is equipped to provide opportunities for graduate and medical students, post-doctoral fellows, and research assistants who are interested in the below described areas of basic and clinical immunology research. Research projects in Dr. Vasu’s Lab are aimed at deep understanding of the immune system so that it can be appropriately manipulated for developing modalities for preventing and treating auto- and allo-immune responses and transplant rejection. His research Laboratory is closely associated with the Labs of Department of Microbiology and Immunology. Dr. Vasu’s current collaborators include Dr. Mark Holterman (Pediatric Surgery), Dr. Bellur Prabhakar (Microbiology and Immunology), Dr. Ernesto Bongarzone (Anatomy and Cell Biology). Dr. Vasu’s research Program has been funded by National Institutes of Health (NIH) and Juvenile Diabetes Research Foundation (JDRF).

Mr. Nicolas Perez, Dr. Subha karumuthil Melethil,  Dr. Ruobing Li, Dr. Chenthamarakshan Vasu

Research Areas of Interest

1) Understanding the function of co-stimulatory and co-repressor molecules in T cell immunity and immune tolerance
Co-stimulatory and co-repressor pathways are considered essential for T cell activation and differentiation. Manipulating these signals on antigen encountered T cells has been considered the most attractive approach in inducing antigen specific T cell tolerance for suppressing or preventing autoimmunity and transplant rejection. Antigen specific tolerance will be the most effective way of inducing T cells tolerance for treating autoimmunity and graft rejection. Antigen specific tolerance approaches have immense potential to treat autoimmune and transplant patients without risking opportunistic infections as well as by eliminating the need for a life long treatment using general immunosuppressive agents. Our studies have shown that this tolerance is associated with an induction and/or expansion of antigen specific regulatory (suppressor) T cells (Tregs). Tregs can suppress effector T cell response and provide long-term sustained protection from autoimmunity and transplant rejection. This project is primarily aimed at understanding the mechanism of costimulatory receptor mediated activation and repressor-receptor mediated modulation of T cell function using knockout and trangenic mouse models. This study will lead not only to the development of effective target-specific therapeutic approach for autoimmunity and transplant rejection, but also in a better understanding of T cell regulation, differentiation, and homeostasis.

2) Understanding the pathogenic T cells and their trafficking properties in autoimmune diabetes
Autoimmune type 1 diabetes (T1D) is caused by selective destruction of insulin producing pancreatic beta cells by our own immune cells. Although it was well known that T cell precursors are originated in the bone marrow (BM), a role for BM in generating, expanding and/or maintaining self-antigen reactive memory T cells was not known before one of our recent reports. Our studies show that pancreatic beta cell destructive memory T cells are present in the BM in large numbers even before the hyperglycemia. Therefore, the primary objective of this project is to understand the properties of autoreactive memory T cell and their preferential trafficking into the BM using type 1 diabetic mouse model. Results from our study will demonstrate the possible applications of BM resident beta cell reactive memory T cells. Based on the outcome, approaches can be developed to exploit BM resident memory T cells to predict T1D in susceptible subjects, reliably monitor the efficacy of immune-therapies, and develop antigen specific safe immune-therapies.

3) Understanding the role of innate immune receptors in autoimmunity
Innate immune response initiated through toll-like receptors (TLRs) and other pattern recognition receptors play both destructive and protective roles in autoimmune diseases. Innate immune stimuli, especially viral and bacterial components, have been implicated in triggering and accelerating autoimmunity through interaction with TLRs and initiating strong inflammatory response. Recently, we reported that innate immune response through TLR2 and dectin 1 receptors can protect NOD mice from autoimmune diabetes by controlling T cell response, suppressing inflammatory pathways of other TLRs, and by enhancing natural regulatory (suppressor) T cell function. Therefore, this project is focused on understanding the role of innate immune signaling pathways in autoimmunity and immune tolerance using autoimmune diabetic mouse model. Ultimate goal of this project is to develop therapeutic modalities using agonistic and/or antagonistic molecules for preventing autoimmunity in susceptible subjects, and suppressing ongoing disease in autoimmune patients.

Relevant publications (selected from last 6 years)

1. Chenthamarakshan Vasu., Wang A, Rao S, Kaithamana S, Prabhakar BS, Holterman MJ. (2003) CD80 and CD86 C domains play an important role in receptor binding and co-stimulatory properties.  Int Immunol. 15 (2): 167-175.

2. Gentile MS, Chenthamarakshan Vasu, Green A, Murillo G, Das Gupta TK, Constantinou AI, Prabhakar BS, Salti GI. (2003) Targeting colon cancer cells with genistein-17.1A immunoconjugate. Int J Oncol;22 (5):955-9.

3.  Chenthamarakshan Vasu, Seema R. Gorla, Bellur S. Prabhakar and Mark J. Holterman. (2003). Targeted engagement of CTLA-4 prevents autoimmune thyroiditis. Int Immunol.15:641.

4.  Dogan RE, Chenthamarakshan Vasu., Holterman MJ, Prabhakar BS. (2003) Absence of IL-4, and Not Suppression of the Th2 Response, Prevents Development of Experimental Autoimmune Graves' Disease.  J Immunol., 170:2195-2204.

5.  Chenthamarakshan Vasu,  Rukiye-Nazan E. Dogan, Mark J. Holterman  and Bellur S. Prabhakar (2003). Selective Induction of Dendritic Cells Using Granulocyte Macrophage-Colony Stimulating Factor, But Not fms-Like Tyrosine Kinase Receptor 3-Ligand, Activates Thyroglobulin-Specific CD4(+)/CD25(+) T Cells and Suppresses Experimental Autoimmune Thyroiditis. J Immunol:170(11):5511-22.

6. Chenthamarakshan Vasu, Mark J. Holterman, Bellur S. Prabhakar (2003) Modulation of Dendritic Cell Function and Cytokine Production to Prevent Thyroid Autoimmunity. Autoimmunity. 36: 389 – 396.

7. Vasu Punj, Suchita Bhattacharyya, Djenann Saint-Dic, Chenthamarakshan Vasu, Elizabeth Cunningham, Jewell Graves, Andreas Constantinou, Konstantin Christov, Bethany White, Gang Li, Dibyen Majumdar, Ananda Chakrabarty, Tapas Das Gupta (2004). Bacterial Cupredoxin Azurin as an inducer of Apoptosis and regression in human breast cancer. Oncogene. 23:2367-2378.

8. Joshua J. Short, Alexander V Pereboev, Chenthamarakshan Vasu, Mark J. Holterman, David T Curiel (2004). Adenovirus Serotype 3 utilizes CD80 (B7.1) and CD86 (B7.2) as primary cellular attachment receptors. Virology. 322:349-359.

9. Chenthamarakshan Vasu, Bellur S. Prabhakar and Mark J. Holterman (2004). Targeted CTLA-4 engagement induces CD4+CD25+CTLA-4high regulatory T cells with target (allo)-antigen specificity. J Immunol; 173:2866-76.

10.       Eryn Gangi, Chenthamarakshan Vasu, Donald Cheatem and Bellur S. Prabhakar (2005) IL-10-producing CD4+CD25+ regulatory T cells play a critical role in granulocyte-macrophage colony-stimulating factor-induced suppression of experimental autoimmune thyroiditis. J Immunol. 174(11):7006.

11. Short JJ, Chenthamarakshan Vasu, Holterman MJ, Curiel DT, Pereboev A. (2006) Members of adenovirus species B utilize CD80 and CD86 as cellular attachment receptors. Virus Res. 122:144-153.

12. Sheng J, Li L, Ganesh BB, Chenthamarakshan Vasu, Prabhakar BS, and Matthew N. Meriggioli. (2006) Suppression of Experimental Autoimmune Myasthenia Gravis (EAMG) by Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is Associated With an Expansion of FoxP3+ Regulatory T Cells. J Immunol. 177(8):5296-306.

13. Ruobing Li, Nicolas Perez, Subha Karumuthil-Melethil, Bellur S. Prabhakar and Mark J. Holterman, Chenthamarakshan 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.

14. Ruobing Li, Nicolas Perez, Subha Karumuthil-Melethil, Chenthamarakshan Vasu. (2007) Bone Marrow is a Preferential Homing site for Autoreactive T cells in type 1 diabetes. Diabetes.; 56 :2251-2259.

15. Francesca Galbiati, Veronica Basso, Ludovico Cantuti, Maria Irene Givogri, Aurora Lopez-Rosas, Nicolas Perez, Chenthamarakshan Vasu, Hongmei Cao, Richard van Breemen, Anna Mondino and Ernesto Bongarzone. Autonomic denervation of lymphoid organs leads to epigenetic immune atrophy in a mouse model of Krabbe disease. J. Neurosci. 2007 Dec 12; 27(50):13730-8.

16. Nicolas Perez, Subha Karumuthil-Melethil, Ruobing Li, Bellur S. Prabhakar and Mark J. Holterman, Chenthamarakshan Vasu. (2008). Preferential costimulation by CD80 results in IL-10 dependent TGF-beta1+ adaptive regulatory T cell generation. J Immunol. 2008 May 15;180(10):6566-76.

17. Sonal Gupta S, Santhakumar Manicassamy, Chenthamarakshan Vasu, Anvita Kumar, Shang W, Zuming Sun. (2008) Differential Requirement of PKC-theta for the development and function of natural regulatory T cells, J. immunol Mol Immunol. 2008 Oct 6. [Epub ahead of print]

18. Subha Karumuthil-Melethil, Nicolas Perez, Ruobing Li, Chenthamarakshan Vasu (2008). Induction of Innate Immune Response through Toll-like Receptor 2 and Dectin 1 prevents type 1 diabetes. J Immunol. December 15. 181 (12):8323-34.

19. Balaji B Ganesh, Donald Cheatem, Jian Rong Sheng, Chenthamarakshan Vasu and Bellur S Prabhakar. GM-CSF induced CD11c+CD8a- DCs suppress autoimmune thyroiditis through the induction of Foxp3+ and IL-10+ T regulatory Cells. (In press: International Immunol).

20. Donald Cheatem, Balaji B Ganesh, Chenthamarakshan Vasu and Bellur S Prabhakar. Modulation of Dendritic Cells Using Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Delays type 1 diabetes by Enhancing CD4+CD25+ Regulatory T Cell Function. (In press: clinical Immunol).

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