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Kanangat
Sivadasan
Ph.D. (Microbiology & Immunology); Diplomat, American Board of Histocompatibility & Immunogenetics {D (ABHI)}
Associate Professor and
Director, Histocompatibility & Immunogenetics
Pathology
GME, Rush Medical College
Jelke Building
1750 W. Harrison
Suite 1109
Chicago, IL 60612
Jelke Building
1750 W. Harrison
Suite 1188
Chicago, IL 60612
(312) 942-2054
sivadasan_kanangat@rush.edu
Christian Medical College, Vellore & Tuberculosis Research Center, University of MADARS, INDIA 1990-MSc, PhD

St. Jude Childrens's Research Hospital: Histocompatibility &Immunogenetics: Director Training-2010

Immune System Diseases
Current Research Areas

Non-HLA immune associated players in Bone Marrow/Hematopoietic Stem Cell Transplantation (BMT/HSCT): Despite allele level matching at 8 or 10 or even 12 loci Graft Vs Host Disease (GVHD) is still a major concern among BMT/HSCT patients. While we are now at a stage where laboratory methodologies are available for near perfect matching, we know that there are several other genes associated with the histocompatibility complex that could play a significant role in the outcome of completely matched transplantation. Some of these are genes involved in cytokine/chemokine expression and pursuit is on for other unexplored genes within the MHC/HLA Complex that are associated with allograft function. We are currently pursuing the effect of polymorphism in genes coding for certain cytokines allowing categorization of patients and donors as High/Low or Intermediate producers of cytokines. The objective is to evaluate the frequency and severity of GVHD in BMT/HSCT patients following transplantation. This study needs a large number of patients due to the heterogeneity of pre-transplant and post transplant management strategies.

Chronic Allograft Rejection: Role of HLA and Non-HLA Endothelial Cell Antibodies in Epithelial/endothelial-Mesenchymal Transition (EMT): Initial allograft acceptance occurs due to lack of any preformed donor specific antibodies (DSAs) that are strong and effective enough to cause graft injuries and dysfunction, no de novo DSA production after transplant and due to successful immunosuppression without any toxicity. However, in mismatched allograft transplants, chronic allograft rejection occurs eventually. Except for genetically identical twins, all allografts are mismatched including that between HLA Identical siblings where there could be mismatches in minor histocompatibility antigens. Almost all allografts undergo chronic rejection due to immunological or non-immunological reasons and remain an unresolved problem in renal transplantation since its pathogenesis is not well understood. Therefore its treatment strategy remains unclear. Chronic rejection seems to be the result of accumulation of damages that occur during early and late post-transplant period. Immune responses, especially humoral responses against HLA and non-HLA antigens, are thought to play critical roles in chronic allograft rejection although the exact mechanisms are not very clear. In most cases by the time the patients are seen post transplant, the chronic rejection would have already set in. So to deal with the chronic rejection, we first need to understand the mechanisms of immune mediated allograft rejection so that research can be directed to develop relevant biomarkers to detect signs of chronic rejection earlier. Also, allograft recipients may develop autoimmunity over a period of time which could react with the endothelial cells antigens of the allograft and lead to the pathogenesis of chronic rejection. The allo and auto immune antibodies could influence the expression of pertinent genes involved in events leading to the pathogenesis of chronic rejection without the participation of complement. Our specific objectives are to understand the role of EMT in interstitial fibrosis, role of HLA and non-HLA endothelial cell antibodies in EMT and identification of genes and proteins involved in these processes. We hope that this information would lead towards the development of newer diagnostic or prognostic markers, and hopefully towards the design and development of novel therapeutic agents to avert chronic allograft rejection.

Selected Publications 
  1. Zhou B, Yuan J, Zhou Y, Yang J, James AW, Nair U, Shu X, Liu W, Kanangat S, Yoo TJ. The attenuation of cockroach allergy by DNA vaccine encoding cockroach allergen Bla g 2. Cell Immunol. 2012, Jul-Aug;278(1-2):120-4.
  2. M. Askar, J. Daghstani, D. Thomas, N. Leahy, P. Dunn F. Claas, S. Doran H. Saji, S. Kanangat, M. Karoichane, A. Tambur, ; D. Monos, M. El-Khalifa,Hamad V. Turner,; M. Kamoun, M. Mustafa, Sheikh Khalifa; D. Ramon, M. Gandhi; A. Vernaza, C. Gorodezky, D. Wagenknecht, M. Gautreaux, A. Hajeer, Z. Kashi, and M. Fernandez-Vina, Stanford University, CA. 2012 16th International HLA and Immunogenetics Workshop (IHIW) Global Distribution of Extended HLA Haplotypes Project: A Preliminary Analysis --- Accepted for Publication in International J I mmunogenetics.
  3. Zhou B, Kermany MH, Glickstein J, Cai Q, Cai C, Zhou Y, Nair U, Kim JW, Kim P, Liu W, Kanangat S, Yoo TJ. 2011. Murine autoimmune hearing loss mediated by CD4+ T cells specific for β-tubulin. Clin Immunol. 2011, Feb;138(2):222-30.
  4. Siva Kanangat, Arnold Postlethwaite, Shaleen Cholera, Latonya Williams and Dennis Schaberg. Modulation of Virulence Gene Expression of S.aureus by IL-1: Novel Implications in Bacterial Pathogenesis. Microbes and Infection-, 9(3):408-415. 2007.
  5. Siva Kanangat, Postlethwaite A, Hasty K, Kang A, Smeltzer M, Appling W, Schaberg D. Induction of multiple matrix metalloproteinases in human dermal and synovial fibroblasts by Staphylococcus aureus: implications in the pathogenesis of septic arthritis and other soft tissue infections. Arthritis Res Ther. 8(6): R176, 2006.
  6. Siva Kanangat, Postlethwaite A. Higgins GC, and Hasty KA. Novel functions of intracellular IL-1receptor antagonist in human dermal fibroblasts: Implications in the pathogenesis of fibrosis (J Invest Dermatol 126: 756-765. 2006.
  7. Postlethwaite AE, Shigemitsu H, and Siva Kanangat. Cellular Origins of Fibroblasts: Possible Implications for Organ Fibrosis in Systemic Sclerosis Arnold E. Current Opinions in Rheumatology. 16: 733-8. 2004. PubMed PMID: 8623544.
  8. Sivadasan Kanangat, Bronze M, Meduri GU, Tolley EA, and Schaberg DR. Enhanced extracellular growth of S. aureus in the presence of selected linear peptide fragments of human IL-1 b and IL-1 receptor antagonist. J Infect Dis 183:65-69. 2001.
  9. Sivadasan Kanangat, Meduri GU, Tolley EA, Patterson DR, Meduri CU, Pak C, Griffin P, Bronze MS, and Schaberg DR. Effects of cytokines and endotoxin on the intracellular growth and survival of bacteria. Infect Immun 67: 2834-2840. 1999.
  10. Thomas J, Sivadasan Kanangat and Rouse BT Herpes simplex virus replication induced expression of chemokines and proinflammatory cytokines in the eye - Implications in herpetic stromal keratitis. J Interferon Cytokine Res 18: 681-690. 1998.
  11. Manickan E, Sivadasan Kanangat, Rouse RJD, Yu Z, and Rouse BT. Enhancement of immune response to naked DNA vaccine by immunization with transfected dendritic cells. J Leuk Biol 64: 125-132. 1997.
  12. Bouley DM, Sivadasan Kanangat and Rouse BT. The role of innate immune system in the reconstituted SCID mouse model of herpetic stromal keratitis. Clin Immunol & Imunopathol 80: 23-30, 1996.
  13. Sivadasan Kanangat, Babu, JS, Knipe DM and Rouse BT. Herpes simplex virus mediated modulation of cytokine gene expression in permissive cell line: selective up - regulation of IL-6 gene expression. Virology 219:29-300. 1996.
  14. Sivadasan Kanangat, Blair P, Reddy R, Daheshia M, Godfrey V, Rouse BT and Wilkinson E. Disease in scurfy mouse is associated with overexpression of cytokine genes. Euro J Immunol 26:161-165 1996, year?
  15. Sivadasan Kanangat, Thomas J, Gangappa S, Babu JS and Rouse BT. Herpes simplex virus mediated up - regulation of IL 12p40 mRNA expression: Implications in immunopathogenesis and protection. J Immunol 156:1110-1116. 1996.
  16. Banks TA, Rouse BT, Kerly MK, Blair PJ, Godfrey VL, Kuklin N, Bouley DM, Thomas J, Sivadasan Kanangat and Muceski ML Lymphotoxin alpha deficient mice: Effects on secondary lymphoid organ development and humoral immune responsiveness. J Immunol 155: 1685-1693. 1995.
  17. Sivadasan Kanangat, Nair S, Babu JS and Rouse BT. Enhanced cytokine mRNA expression in murine dendritic cells and better induction of T cell derived cytokines by dendritic cells than macrophages during in vitro co stimulation assay using specific antigens. J Leuk Biol 57: 310-316. 1995.
  18. Lathey JL, Sivadasan Kanangat, Rouse BT, Agosti JM and Spector M. Dysregulation of cytokine expression in monocytes from HIV positive individuals. J Leukoc Biol 56: 47-352. 1994.
  19. Banks TA, Jenkins FJ, Sivadasan Kanangat, Nair S, Dasgupta S, Foster CM and Rouse BT. Vaccination with the immediate - early protein ICP 47 of herpes simplex virus type 1 induces virus specific lymphoproliferation, but fails to protect against lethal challenge. Virology 200: 236-243. 1994.
  20. Sivadasan Kanangat, Soloman A and Rouse BT. Use of quantitative polymerase chain reaction to quantitate cytokine messenger RNA molecules. Mol Immunol 29:1229-1236. 1992.
  21. Sivadasan Kanangat, Kurien B and John TJ Rapid diagnosis of typhoid fever by antigen detection. Lancet 1: 134–135. 1984.
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