Sunil Kurian

RESEARCH

Kidney transplantation has extended and improved the quality of life for many patients with end stage renal disease. Most transplants involve genetically non-identical donor to recipient combinations. As a consequence the immune response is a major impediment to successful graft survival, necessitating lifelong treatment with potent immunosuppressive drugs. These drugs suppress the host immune system in a nonspecific manner and have many side effects including, but not limited to, increased risk of life threatening infections and cancer. A key point is that the donor organ and its complex responses to transplantation is also a major player in all the events determining the clinical events post transplant. Despite recent reductions in the incidence of acute rejection (AR), chronic allograft nephropathy (CAN) and immunosuppressive drug side effects are still major causes of graft loss and patient morbidity. In this context. We focus on advancing our understanding of the immune response and the responses of the transplanted organ to both immune and non-immune injury mechanisms using high throughput genomic (high density DNA microarrays), proteomic (mass spectroscopy) and complex trait genetic technologies (SNP typing by resequencing).

Our aims are to determine gene expression profiles on transplant biopsies and PBL and identify candidate genes (most of which are presently unknown) that can be correlated with clinical events following kidney transplantation, and to successfully integrate these candidate gene sets for each patient class that can be integrated with the parallel studies of proteomics and complex trait genetics analyses. Since, all biological events are multifactorial and involve a cascade of genes the data obtained will be used to understand the role of these genes in the complex pathways involved in transplantation.

Our other collaborative interests are identification of peripheral blood biomarkers for mood disorders using Convergent Functional Genomics (CFG). Our recent studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and disease state.

Another collaboration we recent have forged is to look at markers of pancreatic islet functionality with respect to islet tranplantation. Given the costs of islet transplantation and the difficulty in predicting islet fuctionality our group in collaboration with THe City of Hope and Methodist Hospital, Houston are determining reliable markers of islet functionality using DNA microarrays and tandem mass spectrometry.

	Position: Staff Scientist Birthday: 14th December, 1972 Nationality: Indian Education: Ph.D., The Tamil Nadu Dr. MGR Medical University, Chennai, India Email: smkurian@scripps.edu	Curriculum vitae	LINKS Transplant Genomics Collaborative Group (TGCG) DNA Array Core

RESEARCH Kidney transplantation has extended and improved the quality of life for many patients with end stage renal disease. Most transplants involve genetically non-identical donor to recipient combinations. As a consequence the immune response is a major impediment to successful graft survival, necessitating lifelong treatment with potent immunosuppressive drugs. These drugs suppress the host immune system in a nonspecific manner and have many side effects including, but not limited to, increased risk of life threatening infections and cancer. A key point is that the donor organ and its complex responses to transplantation is also a major player in all the events determining the clinical events post transplant. Despite recent reductions in the incidence of acute rejection (AR), chronic allograft nephropathy (CAN) and immunosuppressive drug side effects are still major causes of graft loss and patient morbidity. In this context. We focus on advancing our understanding of the immune response and the responses of the transplanted organ to both immune and non-immune injury mechanisms using high throughput genomic (high density DNA microarrays), proteomic (mass spectroscopy) and complex trait genetic technologies (SNP typing by resequencing). Our aims are to determine gene expression profiles on transplant biopsies and PBL and identify candidate genes (most of which are presently unknown) that can be correlated with clinical events following kidney transplantation, and to successfully integrate these candidate gene sets for each patient class that can be integrated with the parallel studies of proteomics and complex trait genetics analyses. Since, all biological events are multifactorial and involve a cascade of genes the data obtained will be used to understand the role of these genes in the complex pathways involved in transplantation. Our other collaborative interests are identification of peripheral blood biomarkers for mood disorders using Convergent Functional Genomics (CFG). Our recent studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and disease state. Another collaboration we recent have forged is to look at markers of pancreatic islet functionality with respect to islet tranplantation. Given the costs of islet transplantation and the difficulty in predicting islet fuctionality our group in collaboration with THe City of Hope and Methodist Hospital, Houston are determining reliable markers of islet functionality using DNA microarrays and tandem mass spectrometry.

Publications: 1. Selvaraj, P., Uma, H., Reetha, A.M., Kurian, S.M. , Theresa Xavier., Prabhakar, R., Narayanan, P.R. HLA antigen profile in pulmonary tuberculosis patients and their spouses. : Indian Journal of Medical Research , 1998, 107-1 155-158. 2. Selvaraj, P., Kurian,S.M., Uma,H., Reetha, A.M. and Narayanan, P.R. Influence of non-MHC genes on lymphocyte response to Mycobacterium tuberculosis antigens and tuberculin status in pulmonary tuberculosis. Indian Journal of Medical Research , 2000, 112, 86-92. 3. Selvaraj, P., Kurian,S.M., ., Reetha, A.M., Niruparani Charles and Narayanan, P.R. Vitamin D receptor and interleukin-1 receptor antagonist gene polymorphism in spinal tuberculosis. Current Science , 2000, 79, 986-989. 4. Kurian,S.M., , Selvaraj, P., Uma Sriram, Chandra, G., Narayanan, P.R. HLA-DR2 phenotype and circulating immune complex level in pulmonary tuberculosis. Biomedicine , 2000, 20, 282-287. 5. Kurian,S.M., , Selvaraj, P., Reetha, A.M., Niruparani Charles, Anila Anna Mathan, Narayanan, P.R. Immune response to Mycobacterium tuberculosis culture filtrate antigen in cured spinal tuberculosis patients and their spouses. Indian Journal of Tuberculosis , 2001, 48, 3-7. 6. Selvaraj, P., Kannapiran, M., Kurian,S.M., , Narayanan, P.R. Effect of plasma lysozyme on live Mycobacterium tuberculosis. Current Science , 2001, 81, 201-203. 7. Uma Sriram, Selvaraj, P., Kurian,S.M., , Reetha, A.M., Narayanan, P.R. HLA-DR2 subtypes & immune responses in pulmonary tuberculosis. Indian Journal of Medical Research , 2001, 113, 117-124. 8. Selvaraj, P., Sriram, U., Kurian,S.M., , Reetha, A.M., Narayanan, P.R. Tumour necrosis factor alpha (-238 and -308) and beta gene polymorphisms in pulmonary tuberculosis : haplotype analysis with HLA-A, B and DR genes. Tuberculosis , 2001, 81, 335-341. 9. Selvaraj, P., Chandra, G., Kurian,S.M., , Reetha, A.M., Charles, N., Narayanan, P.R. NRAMP1 gene polymorphism in pulmonary and spinal tuberculosis. Current Science , 2002, 82, 451-454. 10. Selvaraj, P., Chandra, G., Kurian,S.M., Reetha, A.M., Narayanan, P.R. Association of vitamin D receptor gene variants of Bsm I , Apa I and Fok I polymorphisms with susceptibility or resistance to pulmonary tuberculosis . Current Science , 2003, 84, 1564-1568. 11. Selvaraj, P., Kurian,S.M., Chandra, G., Reetha, A.M., Charles, N., Narayanan, P.R. Vitamin D receptor gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms in spinal tuberculosis Clinical Genetics , 2003, 65, 73-75. 12. *Kurian,S.M.,** Flechner, S.M., Head , S.R., Sharp, S.M., Whisenant, T.C., Zhang, J Chismar, J.D., Horvath, S., Mondala, T., Gilmartin, T., Cook, D, J., Kay, S.A., Walker, J.R and Salomon, D.R. Acute Kidney Transplant Rejection and Tissue Injury Revealed in Gene Profiling Signatures of Biopsies and Peripheral Blood Lymphocytes. American Journal of Transplantation* , 2004 Sep; 4(9): 1475-89. 13. Kurian, S.M., Selvaraj, P., Reetha, A.M., Charles, N., Narayanan, P.R. HLA-DR phenotypes and lymphocyte response to M. tuberculosis antigens in cured spinal tuberculosis patients and their contacts. Indian Journal of Tuberculosis . 2004; 51:71-75 14. Selvaraj, P., Raja, A., Kurian S.M. , Uma Devi, K.R. and P. R. Narayanan. HLA-DR phenotypes and IgG, IgA and IgM antibody responses to Mycobacterium tuberculosis culture filtrate and 30 kDa antigens in pulmonary tuberculosis. Current Science , 2004,87(6), 771-775. 15. Stuart M. Flechner, Sunil M. Kurian , Kim Solez, Daniel J. Cook, James T. Burke, Hank Rollin, Jennifer A. Hammond, Thomas Whisenant, Caroline M. Lanigan, Steven R. Head, and Daniel R. Salomon. De novo kidney transplantation without use of calcineurin inhibitors preserves renal function and histology at two years. American Journal of Transplantation , 2004 Nov;4 (11):1776-85. 16. Yuri Martina, Sunil M Kurian , Stephanie Cherqui, Gabriel Evanoff, Carolyn R Wilson and Daniel R. Salomon. Pseudotyping of Infectious Porcine Endogenous Retrovirus Species by Xenotropic Murine Leukemia Virus in a Pig Islet Xenotransplantation Model. American Journal of Transplantation 2005 Aug;5(8):1837-47. 17. Sunil M Kurian , Stuart M Flechner and Daniel R Salomon. Genomics and Proteomics in Transplantation. Current Opinions in Organ Transplantation . 2005, 10:191-917. 18. Sunil M Kurian , Stuart M Flechner, Jihad Kaouk, Charles Modlin, David Goldfarb, Daniel J Cook, Steven Head and Daniel R Salomon. Laparoscopic Donor Nephrectomy Gene Expression Profiling Reveals Upregulation of Stress and Ischemia Associated Genes When Compared to Open Donor Nephrectomies. Transplantation . 2005 Oct 27;80(8):1067-71. 19. Stephanie Cherqui, Sunil M. Kurian , Olivier Schussler, Johannes A. Hewel, John R. Yates III and Daniel R. Salomon. Isolation, angiogenesis and proteogenomic profiling of endothelial progenitors in the fetal liver. Stem Cells . 2006 Jan 24 (1) 44-54. 20. Stephanie Cherqui, Kenneth Kingdon, Camille Thorpe, Sunil M Kurian and Daniel R. Salomon Lentiviral gene delivery of vMIP-II via both transplanted mature endothelial and progenitor cells enhances angiogenesis in vivo . Molecular Therapy 2007 Jul; 15 ( 7 ): 1264-72 . Epub 2007 May 1. 21. Stuart M. Flechner, David Goldfarb, Kim Solez, Charles S. Modlin, Barbara Mastroianni, Kathy Savas, Denise Babineau, Sunil M Kurian , Daniel Salomon, Andrew C. Novick and Daniel J. Cook. Kidney transplantation with sirolimus and MMF based immunosuppression: 5-year results of a randomized prospective trial compared to calcineurin inhibitor drugs. Transplantation. 2007 Apr 15; 83 ( 7 ): 883-92 . 22. Le-Niculescu H, McFarland MJ, Mamidipalli S, Ogden CA, Kuczenski R, Kurian SM, Salomon DR, Tsuang MT, Nurnberger JI Jr, Niculescu AB. Convergent Functional Genomics of bipolar disorder: from animal model pharmacogenomics to human genetics and biomarkers. Neurosci Biobehav Rev. 2007; 31 ( 6 ): 897-903 . Epub 2007 Jun 3. 23. Sunil M Kurian , Yevgeniy Grigoryev, Steven Head, Daniel Campbell, Tony Mondala , Daniel R. Salomon. Applying genomics to organ transplantation medicine in both discovery and validation of biomarkers. Int Immunopharmacol. 2007 Dec 20; 7 ( 14 ): 1948-60 . Epub 2007 Aug 9. 24. Bayram Edemir, Sunil M Kurian , Martin Eisenacher, Detlef Lang, Carsten Muller-Tidow, Gert Gabriels, Daniel R Salomon and Eberhard Schlatter. Activation of counter-regulatory mechanisms in a rat renal acute rejection model. BMC Genomics . 2008 Feb 8; 9 : 71. 25. H. Le-Niculescu , Sunil M. Kurian , N. Yehyawi, C. Dike, S. Mamidipalli, S.D. Patel, H.J. Edenberg, M. T. Tsuang, D. R. Salomon, J. I. Nurnberger Jr, A. B. Niculescu. Identifying Blood Biomarkers For Mood Disorders Using Convergent Functional Genomics. Accepted for publication in Molecular Psychiatry. Mol Psychiatry . 2008 Feb 26. [Epub ahead of print]. 26. Jeroen de Jonge, Sunil M. Kurian , Daniel R. Salomon, Robert Fisher, Abraham Shaked, and Kim M. Olthoff. Gene expression profile analysis of liver regeneration after human living donor liver transplantation (LDLT). Manuscript in review. 27. Mary Hummel, Sunil M. Kurian , Simon Lin, Alexei Borodyanskiy, Zheng Zhang, Zhigao Li, Soo Jung Kim, Daniel R. Salomon, and Michael Abecassis. TNF contributes to activation of innate and adaptive immunity in early allograft rejection. Manuscript in review. * - Authors contributed equally to the work) Papers presented at Conferences: Sunil Mathan Kurian , P. Selvaraj, A.M. Reetha et al. “Effect of active pulmonary-TB plasma of HLA-DR2 positive and -DR2 negative patients on the lymphocyte response to M. tuberculosis antigen in quiescent patients with TB-spine (extrapulmonary-TB)” presented as poster at XXIV Annual Conference of the Indian Immunology Society held at Calcutta from December 22-24, 1997. Sunil Mathan Kurian , P. Selvaraj, A.M. Reetha et al. “HLA-A, -B, tumour necrosis factor- b ? (TNF- b ) and interleukin-1 receptor antagonist (IL-1RA) gene polymorphism in spinal tuberculosis (extrapulmonary form of tuberculosis)” award winning poster (in Clinical Immunology category) presented at the XXVI Annual Conference of the Indian Immunology Society held at Mumbai from January 13-15, 2000. Sunil Mathan Kurian , P. Selvaraj, A.M. Reetha, Niruparani Charles, G. Chandra and P.R. Narayanan. “Influence of vitamin D receptor gene ( Taq I & Bsm I) polymorphism on lymphocyte response to Mycobacterium tuberculosis culture filtrate antigen in cured spinal tuberculosis patients” presented as poster at International symposium on Mycobacterial diseases: pathogenesis, protection and control held at Calcutta from 9-11 January, 2001. Sunil Kurian , Stuart M. Flechner, Steven Head, Starette Sharp, Thomas Whisenant, Jie Zhang, Jefferey Chismar, Tony Mondala, Daniel J. Cook, John Walker, Daniel Salomon. Characterizing Renal Transplant Rejection and Immunosuppression By Gene Profiling of Biopsies and Peripheral Blood Lymphocytes. American Transplant Congress, Washington DC , May 30 – June 4, 2003. Stuart M. Flechner, Kim Solez, Daniel J. Cook, James T. Burke, Hank Rollin, Barbara Mastoianni, Kathy Savas, Sunil Kurian , Steven Head, Daniel R. Salomon. Kidney Transplantation With Sirolimus And Mycophenolate Mofetil Based Immunosuppression Preserves Renal Structure And Function Compared To Calcineurin Inhibitor (CNI) Drugs. American Transplant Congress, Boston , May 14 – May 19, 2004. Sunil M. Kurian , Stuart M. Flechner, Jihad Kaouk, Charles Modlin, David Goldfarb, Daniel J. Cook, Steven Head and Daniel R. Salomon. Laparoscopic Donor Nephrectomy Gene Expression Profiling Reveals Upregulation of Stress and Ischemia Associated Genes Compared to Control Kidneys. American Transplant Congress, Seattle, May 21 – May 25, 2005. Jeroen de Jonge, Sunil Kurian , Daniel R. Salomon, Hugo W. Tilanus, Luc van der Laan, Kim M. Olthoff. Gene expression profile of regeneration in human Living-donor liver transplantation . International Liver Transplant Society Meeting, Milan , Italy , May 3-6, 2006. Sunil M Kurian , Stuart Flechner, Lana Schaffer, Johannes Hewel, Steve Head, Steve Horvath, John Yates III, Daniel Salomon. A systems biology approach to molecular profiling of chronic allograft nephropathy using peripheral blood lymphocytes. World Transplant Congress, Boston , MA , July 22-28, 2006. Johannes A Hewel, Sunil M Kurian , Stuart M Flechner, John R Yates III, Daniel R Salomon. “Proscript-profiling” proteogenomics of chronic allograft nephropathy. World Transplant Congress, Boston , MA , July 22-28, 2006. Stuart M Flechner, David Goldfarb, Kim Solez, Charles S Modlin, Barbara Mastroianni, Kathy Savas, Lingmei Zhou, Sunil M Kurian , Daniel Salomon, Daniel J Cook. Kidney transplantation with sirolimus and mycophenolate mofetil based immunosuppression: 5-year results of a randomized prospective trial compared to calcineurin inhibitor (CNI) drugs. World Transplant Congress, Boston , MA , July 22-28, 2006. Sunil Kurian, Kim Olthoff, Jeroen deJonge, Abraham Shaked and Daniel Salomon. Unique Gene Expression Patterns In Brain Dead Deceased Donor Liver Grafts At Time Of Procurement. American Transplant Congress, San Francisco, CA, May 5-10, 2007. Memberships: American Society of Transplantation 2007 Honors: Junior Research Fellowship (1995)and Senior Research Fellowship (1998), Council for Scientific and Industrial Research (CSIR), India. Young Investigator Award, American Transplant Congress, San Francisco, CA, May 5-10, 2007. Talks Given: Proteogenomics of PBL & Whole Blood in Patients with Chronic Allograft Nephropathy Reveals Strong Correlations with Immunity and Candidate Biomarkers for Early Stage Chronic Allograft Nephropathy. Sunil Kurian, Johannes Hewel, Lin Wang, Stuart Flechner, Lillian Gaber, Christopher Marsh, Daniel Campbell, Tony Mondala, Steve Head, Steve Horvath, John Yates, Daniel Salomon. Talk given at American Transplant Congress, San Francisco, CA, May 5-10, 2007. Genomic Approaches to Alternative and Complementary Medicine. Sunil Kurian, Aleksey Nakorchevskiy, Johannes Hewel, Daniel Campbell, Elizabeth Robison, Tony Mondala, Steven Head, John Yates & Daniel Salomon. ICHM 2008. Ist International Euro-India Conference on Holistic Medicine. Kottayam, Kerala, India, August 21-23, 2008. Conferences Attended: Tuberculosis Research: Into the 21st century. A workshop sponsored by Indian Council of Medical Research (ICMR), Department of Science and Technology, Govt. of India and Indo-UK DFID (Dept. for International Development) organized by Tuberculosis Research Centre, from 3-5 February 1998 Sixth Asia-Oceania Histocompatibility Conference held in New Delhi from 29th October to 1st November 1998. XXVI Annual Conference of the Indian Immunology Society held at Mumbai from January 13-15, 2000. Indo-French workshop on tuberculosis held at Tuberculosis Research Centre, Chennai on 1st and 2nd December 2000. International symposium on Mycobacterial diseases: pathogenesis, protection and control held at Calcutta from 9-11 January 2001. American Transplant Congress, Washington DC , May 30 – June 4, 2003. Thomas Starzl Transplant Fellows Symposium, Scottsdale , AZ , November 4-6, 2005. World Transplant Congress, Boston , MA , July 22-28, 2006. American Transplant Congress, San Francisco, CA, May 5-10, 2007. ICHM 2008. Ist International Euro-India Conference on Holistic Medicine. Kottayam, Kerala, India, August 21-23, 2008.