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Gattadahalli S. Seetharam, PhD
Assistant Professor of Biochemistry & Molecular Biology
Dr. Seetharam is the Evansville Course Director for the MS1 course - Molecules to Cells and Tissues (MCT) and MS2 course - Endocrinology and Reproductive Biology (ERB). He serves on the IUSM Curriculum Council Foundational Component Committee (FCC) and is Research Liaison to the IUSM for the Evansville Center. He is a member of IUSM curriculum committee involved in the creation of new integrated curriculum.
Dr. Seetharam’s research interest is to investigate the molecular mechanisms autoimmune Graves’ disease (GD). His research have focused on the identification of specific intracellular signaling molecules, costimulatory molecules and cytokine targets that may be significant for therapeutic intervention of GD. His research has been funded by American Heart Association, American Thyroid Association, and National Institutes of Health. He is a member of Endocrine Society and American Thyroid Association.
1. Coming together for IPEC: The Ohio Valley Collaborative. Elizabeth Kalb, Jane Friona, Mary Kessler, Cynthia Moore and Seetharam GS. 2nd Annual Interprofessional Practice and Education Conference, IUPUI Campus Center, Indianapolis, November 15, 2017.
2. Integration of Effective Communication and Lifelong Learning Competencies into Medical Biochemistry Curriculum.
Seetharamaiah GS, Anthony TG. 4th international conference of the Association of Biochemistry Course Directors (ABCD), Santa Fe, NM May 05-09, 2013.
1. Differential Susceptibility of BALB/c and BALB/cBy mice to Graves' hyperthyroidism.
Seetharamaiah GS, Land KJ. Thyroid. 2006 Jul;16(7):651-8.
2. Differential requirement of signal transducer and activator of transcription-4 (Stat4) and Stat6 in a thyrotropin receptor-289-adenovirus-induced model of Graves' hyperthyroidism. Land KJ, Gudapati P, Kaplan MH, Seetharamaiah GS. Endocrinology. 2006 Jan;147(1):111-9.
3. Signal transducer and activator of transcription (Stat)-6-dependent, but not Stat4-dependent, immunity is required for the development of autoimmunity in Graves' hyperthyroidism. Land KJ, Moll JS, Kaplan MH, Seetharamaiah GS. Endocrinology. 2004 Aug;145(8):3724-30.
4. Animal models of Graves' hyperthyroidism.
Seetharamaiah GS. Autoimmunity. 2003 Sep-Nov;36(6-7):381-7. Review.
5. Relevance of differential immunogenicity of human and mouse recombinant desmoglein-3 for the induction of acantholytic autoantibodies in mice.
Kaithamana S, Fan JL, Memar O, Li K, Uitto J, Seetharamaiah GS, Prabhakar BS. Clin Exp Immunol. 2003 Apr;132(1):16-23.
6. Studies using recombinant fragments of human TSH receptor reveal apparent diversity in the binding specificities of antibodies that block TSH binding to its receptor or stimulate thyroid hormone production.
Cundiff JG, Kaithamana S, Seetharamaiah GS, Baker JR Jr, Prabhakar BS. J Clin Endocrinol Metab. 2001 Sep;86(9):4254-60.
7. Regulation of thyrotropin receptor protein expression in insect cells.
Seetharamaiah GS, Kaithamana S, Desai RK, Prabhakar BS. J Mol Endocrinol. 1999 Dec;23(3):315-23.
8. Selective binding of thyrotropin receptor autoantibodies to recombinant extracellular domain of thyrotropin/lutropin-chorionic gonadotropin receptor chimeric proteins.
Seetharamaiah GS, Zhuang J, Huang J, Patibandla SA, Kaithamana S, Tahara K, Kohn LD, Prabhakar BS. Thyroid. 1999 Sep;9(9):879-86.
9. Comparison of immune responses to extracellular domains of mouse and human thyrotropin receptor.
Patibandla SA, Fan JL, Prabhakar BS, Seetharamaiah GS. J Autoimmun. 1999 Sep;13(2):205-13.
10. Neuroendocrine-induced synthesis of bone marrow-derived cytokines with inflammatory immunomodulating properties.
Whetsell M, Bagriacik EU, Seetharamaiah GS, Prabhakar BS, Klein JR. Cell Immunol. 1999 Mar 15;192(2):159-66.
11. Glycosylated ectodomain of the human thyrotropin receptor induces antibodies capable of reacting with multiple blocking antibody epitopes.
Seetharamaiah GS, Dallas JS, Prabhakar BS. Autoimmunity. 1999;29(1):21-31.
12. Thyrotropin-receptor-mediated diseases: a paradigm for receptor autoimmunity.
Prabhakar BS, Fan JL, Seetharamaiah GS. Immunol Today. 1997 Sep;18(9):437-42. Review.
13. Flow cytometric analyses of antibody binding to Chinese hamster ovary cells expressing human thyrotropin receptor.
Patibandla SA, Dallas JS, Seetharamaiah GS, Tahara K, Kohn LD, Prabhakar BS. J Clin Endocrinol Metab. 1997 Jun;82(6):1885-93.
14. Differential reactivities of recombinant glycosylated ectodomains of mouse and human thyrotropin receptors with patient autoantibodies.
Patibandla SA, Seetharamaiah GS, Dallas JS, Thotakura NR, Peake RL, Prabhakar BS. Endocrinology. 1997 Apr;138(4):1559-66.
15. Requirement of glycosylation of the human thyrotropin receptor ectodomain for its reactivity with autoantibodies in patients' sera.
Seetharamaiah GS, Dallas JS, Patibandla SA, Thotakura NR, Prabhakar BS. J Immunol. 1997 Mar 15;158(6):2798-804.
16. Lipoprotein from Yersinia enterocolitica contains epitopes that cross-react with the human thyrotropin receptor. Zhang H, Kaur I, Niesel DW, Seetharamaiah GS, Peterson JW, Prabhakar BS, Klimpel GR. J Immunol. 1997 Feb 15;158(4):1976-83.
17. Purification and characterization of a recombinant human thyroid peroxidase expressed in insect cells.
Fan JL, Patibandla SA, Kimura S, Rao TN, Desai RK, Seetharamaiah GS, Kurosky A, Prabhakar BS. J Autoimmun. 1996 Aug;9(4):529-36.
18. Yersinia enterocolitica envelope proteins that are crossreactive with the thyrotropin receptor (TSHR) also have B-cell mitogenic activity.
Zhang H, Kaur I, Niesel DW, Seetharamaiah GS, Peterson JW, Justement LB, Prabhakar BS, Klimpel GR. J Autoimmun. 1996 Aug;9(4):509-16.
19. Thyrotropin (TSH) receptor antibodies (TSHrAb) can inhibit TSH-mediated cyclic adenosine 3',5'- monophosphate production in thyroid cells by either blocking TSH binding or affecting a step subsequent to TSH binding.
Dallas JS, Cunningham SJ, Patibandla SA, Seetharamaiah GS, Morris JC, Tahara K, Kohn LD, Prabhakar BS. Endocrinology. 1996 Aug;137(8):3329-39.
20. Recombinant desmoglein 3 has the necessary epitopes to adsorb and induce blister-causing antibodies.
Memar OM, Rajaraman S, Thotakura R, Tyring SK, Fan JL, Seetharamaiah GS, Lopez A, Jordon RE, Prabhakar BS. J Invest Dermatol. 1996 Feb;106(2):261-8.
21. Influence of adjuvants on the induction of autoantibodies to the thyrotropin receptor.
Seetharamaiah GS, Fan JL, Patibandla SA, Prabhakar BS. Autoimmunity. 1996;24(4):205-15.
22. Experimental autoimmunity to thyrotropin receptor.
Patibandla SA, Wagle NM, Seetharamaiah GS, Fan JL, Dallas JS, Prabhakar BS. Exp Clin Endocrinol Diabetes. 1996;104 Suppl 3:28-32.
23. Generation and characterization of monoclonal antibodies to the human thyrotropin (TSH) receptor: antibodies can bind to discrete conformational or linear epitopes and block TSH binding.
Seetharamaiah GS, Wagle NM, Morris JC, Prabhakar BS. Endocrinology. 1995 Jul;136(7):2817-24.
24. A region on the human thyrotropin receptor which can induce antibodies that inhibit thyrotropin-mediated activation of in vitro thyroid cell function also contains a highly immunogenic epitope.
Dallas JS, Seetharamaiah GS, Cunningham SJ, Goldblum RM, Desai RK, Prabhakar BS. J Autoimmun. 1994 Aug;7(4):469-83.
25. High frequency of B cells capable of producing anti-thyrotropin receptor antibodies in patients with Graves' disease.
Fan JL, Desai RK, Dallas JS, Wagle NM, Seetharamaiah GS, Prabhakar BS. Clin Immunol Immunopathol. 1994 Apr;71(1):69-74.
26. Thyrotropin (TSH) interacts with multiple discrete regions of the TSH receptor: polyclonal rabbit antibodies to one or more of these regions can inhibit TSH binding and function. Dallas JS, Desai RK, Cunningham SJ, Morris JC, Seetharamaiah GS, Wagle N, Goldblum RM, Prabhakar BS. Endocrinology. 1994 Mar;134(3):1437-45.
27. Purification and characterization of Yersinia enterocolitica envelope proteins which induce antibodies that react with human thyrotropin receptor.
Luo G, Seetharamaiah GS, Niesel DW, Zhang H, Peterson JW, Prabhakar BS, Klimpel GR. J Immunol. 1994 Mar 1;152(5):2555-61.
28. A recombinant extracellular domain of the thyrotropin (TSH) receptor binds TSH in the absence of membranes.
Seetharamaiah GS, Kurosky A, Desai RK, Dallas JS, Prabhakar BS. Endocrinology. 1994 Feb;134(2):549-54.
29. Induction of hyperthyroxinemia in BALB/C but not in several other strains of mice. Wagle NM, Dallas JS, Seetharamaiah GS, Fan JL, Desai RK, Memar O, Rajaraman S, Prabhakar BS. Autoimmunity. 1994;18(2):103-12.
30. Heterogeneity in cellular and antibody responses against thyrotropin receptor in patients with Graves' disease detected using synthetic peptides.
Fan JL, Desai RK, Seetharamaiah GS, Dallas JS, Wagle NM, Prabhakar BS. J Autoimmun. 1993 Dec;6(6):799-808.
31. Dual mechanism of perturbation of thyrotropin-mediated activation of thyroid cells by antibodies to the thyrotropin receptor (TSHR) and TSHR-derived peptides. Desai RK, Dallas JS, Gupta MK, Seetharamaiah GS, Fan JL, Tahara K, Kohn LD, Prabhakar BS. J Clin Endocrinol Metab. 1993 Sep;77(3):658-63.
32. Immunization of mice with Yersinia enterocolitica leads to the induction of antithyrotropin receptor antibodies.
Luo G, Fan JL, Seetharamaiah GS, Desai RK, Dallas JS, Wagle N, Doan R, Niesel DW, Klimpel GR, Prabhakar BS. J Immunol. 1993 Jul 15;151(2):922-8.
33. Analysis of autoantibody reactivity in patients with Graves' disease using recombinant extracellular domain of the human thyrotropin receptor and synthetic peptides.
Fan JL, Seetharamaiah GS, Desai RK, Dallas JS, Wagle NM, Prabhakar BS. Autoimmunity. 1993;15(4):285-91.
34. Induction of TSH binding inhibitory immunoglobulins with the extracellular domain of human thyrotropin receptor produced using baculovirus expression system.
Seetharamaiah GS, Desai RK, Dallas JS, Tahara K, Kohn LD, Prabhakar BS. Autoimmunity. 1993;14(4):315-20.
35. Comparative hypocholesterolemic activities of oryzanol, curcumin and ferulic acid in rats.
Seetharamaiah GS, Chandrasekhara, N. J. Food Sci. Technol. 30:249-252, 1993.
36. Prokaryotic expression of the thyrotropin receptor and identification of an immunogenic region of the protein using synthetic peptides.
Takai O, Desai RK, Seetharamaiah GS, Jones CA, Allaway GP, Akamizu T, Kohn LD, Prabhakar BS. Biochem Biophys Res Commun. 1991 Aug 30;179(1):319-26.
37. Effect of oryzanol on cholesterol absorption & biliary & fecal bile acids in rats.
Seetharamaiah GS, Chandrasekhara N. Indian J Med Res. 1990 Dec;92:471-5.
38. Influence of oryzanol on platelet aggregation in rats.
Seetharamaiah GS, Krishnakantha TP, Chandrasekhara N. J Nutr Sci Vitaminol (Tokyo). 1990 Jun;36(3):291-7.
39. Studies on hypocholesterolemic activity of rice bran oil.
Seetharamaiah GS, Chandrasekhara N. Atherosclerosis. 1989 Aug;78(2-3):219-23.
40. Effect of oryzanol on fructose induced hypertriglyceridaemia in rats.
Seetharamaiah GS, Chandrasekhara N. Indian J Med Res. 1988 Sep;88:278-81.
41. Hypocholesterolemic activity of oryzanol in rats.
Seetharamaiah GS, Chandrasekhara N. Nutr. Rep. Int. 38:927, 1988.
42. Oryzanol content of Indian rice bran oil and its extraction from soap stock.
Seetharamaiah GS, Prabhakar JV. J. Food Science Technology. 23:270, 1986.
Titles & Appointments
- Assistant Professor of Microbiology & Immunology
Dr. Seetharam’s research interest is to investigate the molecular mechanisms of Graves’ disease (GD). GD is an autoimmune disorder of the thyroid gland characterized by hyperthyroidism and is caused by stimulatory antibodies to thyrotropin receptor (TSHR). Although the GD is mediated primarily by antibodies, the generation of antibodies requires T cell help. Naïve CD4+ T cells, after encounter with an antigen, functionally differentiate into Th1, Th2 or Th17 cells.
Cytokines are the dominant factors guiding the development of Th1/Th2/Th17 cells. We are investigating the role of intracellular transcription factors (STAT4, T-bet, GATA-3 and ROR gt) which regulate the development of Th1/Th2/Th17 cells. Optimal activation of naïve T cells requires at least two signals. Signal one is delivered by engagement of T cell receptor on T cells and peptide-MHC complex on antigen presenting cells (APC).
Signal two is provided by costimulatory molecules on APC binding to their receptors/ligands on T cells. We are exploring the role of different costimulatory molecules during the development of GD. With the availability of a mouse model for GD, we utilize knockout mice, recombinant proteins, monoclonal antibodies and synthetic peptides in our studies. We employ molecular biological, biochemical and immunological approaches to study the structure-function relationship of TSHR and to map functional epitopes.
Together, our studies are expected to lead to the identification of specific intracellular signaling molecules, costimulatory molecules and cytokine targets that may be significant for therapeutic intervention of GD.