GABOR JOSEPH TIGYI, Ph.D., M.D., B.S.

Harriet Van Vleet Professor and Chair
Foreign Member of the Hungarian Academy of Sciences
Member of the European Academy of Arts Letters and Science Paris

Office: 427c Nash Research Building
Tel: (901) 448-2634
gtigyi@uthsc.edu

Education

  • Ph.D., Hungarian Academy of Sciences Budapest, Cellular Biochemistry
  • PostDoc, Laboratory of Cellular & Molecular Neurobiology, U. of California, Irvine, Cellular & Molecular neurobiology
  • Ph.D., Hungarian Academy of Sciences Budapest, Cellular Biochemistry
  • M.D., University Medical School of Pecs, Hungary, General Medicine
  • M.D., University Medical School of Pecs. Hungary, General Medicine
  • B.S., University Medical School of Pecs, Hungary, PreMedical Science
  • B.S., University Medical School of Pecs. Hungary, PreMedical Science

Research interest/specialty

LPA GPCR and PPARgamma receptors in neointima formation.

Research description

Dr. Tigyi's research is aimed at elucidating the structure and function as well as the signal transduction mechanism of a family of endogenous phospholipids with growth factor-like properties. Dr. Tigyi has shown that serum contains a set of lipid factors that are the major source of mitogenic stimuli present in serum. The best characterized member of this group of lipid mediators is lysophosphatidic acid (LPA). Dr. Tigyi's group has identified the PSP24 receptor gene for LPA and has determined the ligand binding pocket for the EDG family of sphingosine-1-phosphate receptors and LPA receptors. Dr. Tigyi's group has made pioneering contributions to the current understanding of the pharmacology of phospholipid growth factors.

Publications

  1. Zhang, Q, Wang, D, Kundumani-Sridharan, V, Gadiparthi, L, Johnson, DA, Tigyi, GJ, Rao, GN. PLD1-dependent PKC{gamma} activation downstream to Src is essential for the development of pathological retinal neovascularization. Blood, 2010.
  2. Jiang, G., Xu, Y., Fujiwara, Y., Tsukahara, R., Tigyi, G., and Prestwich, G.D.. α-Substituted Phosphonate Analogues of Lysophosphatidic Acid (LPA) Selectively Inhibit Production and Action of LPA. Journal of Medicinal Chemistry - in press, 2007.
  3. Jujiwara, Y., Osborne, D.A., Walker, M.D., Wang, D-A, Bautista, D.D., Liliom K., Van Brocklyn, J.R., Parrill, A.L., Tigyi, G.. Identification of the hydrophobic ligand binding pocket of the s1p(1), receptor. Journal of Biological Chemistry, 282 (4), 2374-2385, 2007.
  4. Deng, W., E, S., Tsukahara, R., Valentine, W., Durgam, G., Gududuru, V., Balazs, L., VanMiddlesworth, L., Johnson, L.R., Manickam, V., Arsura, M. Parrill, A.L., Miller, D.D. and Tigyi, G.. The LPA(2) Receptor is Required for Protection Against Radiation-Induced Intestinal Injury. Gastroenterology - in press, 2007.
  5. Gajewiak, J., Yu, S., Tsukahara, R., Tigyi, G., Mills, G.B., Prestwich, G.D. Alkoxymethylenephosphonate Analogues of (Lyso)phosphatidic acid: Synthesis and Biological Activity. Journal of Organic Chemistry - In press, 2007.
  6. Pyne, N.J., Waters, C.M., Long, JS, Moughal, NA, Tigyi, G, and Pyne, S.. Receptor tyrosine kinase-G-protein coupled receptor complex signaling in mammalian cells. Advances in Enzyme Regulation, 2007.
  7. Hao, F., Tan, M., Xu, X., Han, J., Miller, D.D., Tigyi, G., and Cui, M-Z. LPA1 Controlled, p42 and p38α MAPK Regulated Prostate Cancer PC3 Cell Migration induced by Lysophosphatidic Acid. Biochimica et Biophysica Acta. International Journal of Biochemistry and Biophysics - accepted for publication, 2007.
  8. Uchiyama, A., Mukai, M., Kobayashi, S., Kawai, N., Enoki, S., Tanaka, S., Murofushi, H., Niki, T., Kobayashi, T., Tigyi, G., Murakami-Murofushi, K.,. Inhibition of tumor cell invasion and metastasis by novelcarba-derivatives of cyclic phosphatidic acid. Biochimica et biophysica acta. International Journal of Biochemistry and Biophysics., 1771 (1), 103-112, 2007.
  9. Waters, C.M., Connell, M., Gorchkova, I., Long, J., Fujiwara, Y., Belmonte, K., Tigyi, G., Natarajan, W., Pyne, S., and Pyne, N.J.. The sphingosine 1-phosphate receptor-1 inverse agonist SB649146 reduces platelet-derived growth factor-induced cell migration.. FASEB Journal, 20 (3), 509-511, 2006.
  10. Nusser, N., Gosmanova, E., Fujiwara, Y., Makarova, N., Guo, F., Luo, Y., Zheng, Y., and Tigyi, G.. Phosphorylation-regulated Target Selection of RhoA Is Required for NGF-Induced Neurite Outgrowth. Cellular Signaling, 18, 704-714, 2006.
  11. Moughal, N.A., Waters, C.M., Valentine, W.J., Cornell, M., Crook, B., Harrison, S., Richardson, J., Tigyi, G., Pyne, S., Pyne, N.J.,. Cross talk regulation between RrkA and lysophosphatidic acid receptors signaling systems in mammalian cell. Journal of Neurochemistry, 10, 1471-1481, 2006.
  12. Pilquil, C., Dewald, J., Cheney, A., Gorshkova, I., Tigyi, G., English, D., Natarajan, W., and Brindley, D.N.. Lipid Phosphate Phosphatase-1 Regulates Lysophosphatidate-induced Fibroblasts Migration by Controlling Phospholipase D2-dependent Phosphatidate Generation. Journal of Biological Chemistry, 281 (50), 38418-29, 2006.
  13. Naor, M., Walker, D.M., Tigyi, G., Vanbrocklyn, J., Parrill, A.. Sphingosine 1-Phosphate pKa and Binding Constants: Intramolecular and Intermolecular Influences. Proteins - submitted Pending versions, 2006.
  14. Liliom, K., Tsukahara, T., Tsukahara, R., Zelman-Femiak, M., Swiezewska, E., and Tigyi, G.. Farnesyl phosphates are endogenous ligands of lysophosphatidic acid receptors: inhibition of LPA CPCR and activation of PPARg. Biochimica et Biophysica Acta. International Journal of Biochemistry and Biophysics, 1761 (12), 1506-1514, 2006.
  15. Xu, Y., Tsukahara, R., Fujiwara, R., Tigyi, G., and Prestwich, G.. Phosphatidic Acid: Novel pKa Matched LPA Receptors Antagonists. Journal of Medicinal Chemistry, 49, 5309-5315, 2006.
  16. Gududuru, V., Tsukahara, R., Makarova, N., Fujiwara, Y., Pigg, K.R., Baker, D.L., Tigyi, G., and Miller, D.D.. Identification of Darmstoff analogs as selective agonists and antagonists of lysophosphatidic acid receptors. Letters in Applied Biomedical Chemistry 5, 16 (2), 451-456, 2006.
  17. Drugam, G., Tsukahara, R., Makarova, N., Fujiwara, Y., Pigg, K.R., Baker, D.L., Parrill, A., Tigyi, G., and Miller, D.D.. Synthesis and pharmacological evaluation of second-generation phosphatidic derivatives as lysophosphatidic acid receptor ligands. Letters of Applied Biomedical Chemistry, 6 (3), 633-640, 2006.
  18. Li, Z., Baker, D.L., Tigyi, G., and Bittman, R.. Photoactivatable Analogues of Lysophosphatidic Acid and Covalent Labeling of Plasma Proteins. Journal of Organic Chemistry, 71 (20), 629-635, 2006.
  19. Qian, L., Xu, Y., Simper, Y., Aoki, J., Tsukahara, R., Makarova, N., Yu, S., Mills, G.B., Tigyi, G., and Prestwich G.D.. Phosphorothioate and fluoromethylene phosphonate analogues of cyclic phosphatidic Acid: novel antagonists of lysophosphatidic Acid receptors. Chem. Med. Chem, 1, 376-383, 2006.
  20. Zhang, H., Tsukahra, R., Tigyi, G., and Prestwich, G.. Synthesis of Cyclic Phosphonate Analogues of (Lyso)phosphatidic Acid Using a Ring-Closing Metathesis Reaction. Journal of Organic Chemistry, 71 (16), 6061-6066, 2006.
  21. Tsukahara, T., Tsukahara, R., Yasuda, S., Makarova, N., Velentine, W.J., Allison, P., Yuan, H., Baker, D.L., Li, Z., Bittman, R., Parrill, A., and Tigyi, G.. Different Residues Mediate Recognition of 1-O-Oleyl-Lysophosphatidic Acid and Rosiglitazone in the Ligand Binding Domain of PPARγ. Journal of Biological Chemistry, 281 (6), 3398-3407, 2006.
  22. Long, J.S., Darroch, P., Tate, R.J., Tolan, D.J., Tigyi, G., Pyne, N.J., and Pyne, S.. Lipid phosphate phosphatases are functionally active as dimers. Biochemistry Journal, 394, 495-500, 2006.
  23. Baker, D.L., Fujiwara, Y., Pigg, K.R., Tsukahara, R., Kobayashi, S., Uchiyama, A., Murakami-Murofushi, K., Murofushi, H., Koh, E., Bandle, R., Byun, H.-S., Bittman, R., Murph, M., Fan, D., Mills, G.B., Tigyi, G.. Carba Analogs of Cyclic Phosphatidic Acid Are Selective Inhibitors of Autotaxin and Cancer Invasion. Journal of Biological Chemistry, 281, 22786-93, 2006.
  24. Waters, C.M., Saatian B., Moughal N.A., Zhao, Y., Tigyi, G., Natarajan V., Pyne, S., Pyne, N.J.. Integrin signaling regulates the nuclear localization and function of the lysophosphatidic acid receptor-1 (LPA 1) in mammalian cells. Journal of Biochemistry, 398, 55-62, 2006.
  25. Yue, J. and Tigyi, G.. MircroRNA trafficking and Human Cancer. Cancer Biol.Ther., 5, 573-578, 2006.
  26. Li, C, Dandridge, KS, Di, A, Marrs, KL, Harris, EL, Roy, K, Jackson, JS, Makarova, NV, Fujiwara, Y, Farrar, PL, Nelson, DJ, Tigyi, GJ, Naren, AP. Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions. J Exp Med, 202 (7), 975-86, 2005.
  27. Inagaki, Y., Kohno, T., Pham, T-C, T, Fujiwara, Y., Igarashi, Y., Tigyi, G., and Parrill, A.L.. Distinct and Conserved Residues Mediate Sphingosine-1-Phosphate Recognition in S1P(4) within the Endothelial Differentiation Gene Family of Receptors. Biochemical Journal, 89, 187-195, 2005.
  28. Jo, E., Sanna, M.G., Gonzalez-Caberra, P.J., Thangada, S., Tigyi, G., Osborne, D.A., Hla, T., Parrill, A.L., Rosen, H.. S1P1-selective in vivo-active agonists from high throughput screening: Off the shelf chemical probes of receptor interactions, signaling and fate. Chemistry & Biology, 12, 703-715, 2005.
  29. Krump-Konvalinkova, V., Yasuda, S., Rubic, T., Makarova, N., Mages, J., Erl, W., Vosseler, C., Kirkpatrick, C.J., Tigyi, G., and Siess, W.. Stable knock-down of the sphingsoine-1-phosphate receptor S1P1 influences multiple functions of human endothelial cells. Atherosclerosis Vascular Biology, 25 (3), 546-552, 2005.
  30. Fujiwara, Y., Sardar, V., Tokumura, A., Baker, D.L., Murakami-Murofushi, K., Parrill, A., and Tigyi, G.. Identification of residues responsible for ligand recognition and regiosomeric selectivity of LPA receptors expressed in mammalian cells. Journal of biological chemistry, 280, 35038-50, 2005.
  31. Durgam, G.G., Virag, T., Walker, M.D., Tsukahara, R., Yasuda S., Liliom, K., van Meeteren, L.A., Moolenaar, W.H., Wilke, N., Siess, W., Tigyi, G., and Miller, D.D.. Synthesis, Structure-Activity Relationships, and Biological Evaluation of Fatty Alcohol Phosphates as Lysophosphatidic Acid Receptor Ligands, Activators of PPARγ and Inhibitors of Autotaixin. Journal of medicinal chemistry, 48 (15), 4919-4930, 2005.
  32. Goetzl, EJ, and Tigyi, G.. Lysophospholipids and their G protein-coupled receptors in biology and diseases.. Journal of Cellular Biochemistry, 92 (5), 867-868, 2004.
  33. Li, C. Dandridge, K.S., Harris, E.L., Roy, K., Jackson, J.S., Makarova, N.V., Farrar, P.L., Tigyi, G. and Naren A.P.. Lysophophatidic inhibition of secretory diarrhea through CFTR-dependent protein interactions. Science-in review, 2004.
  34. Deng, W., Poppleton, H., Yasuda, S., Makarova, N., Shinozuka, Y., Wang, D-A., Johnson, L.R., Patel, T.B., and Tigyi, G.. Optimal LPA-induced DNA Synthesis and Cell Migration but Not Survival Require Intact Autophosphorylation Sites of the EGF Receptor., 279, 47871-80, 2004.
  35. Zhang, C., Baker, D.L., Yasuda, S., Makarova, N., Balazs, L., Johnson, L.R., Marathe, G.K., McIntyre, T.M., Xu, Y., Prestwich, G.D., Byun, H-S., Bittman R., and Tigyi, G.. Lysophosphatidic Acid Induces Neointima Formation Through PPARγ Activation. Journal of Experimental Medicine, 199, 763-774, 2004.
  36. Siess, W., and Tigyi, G.. Thrombogenic and athergenic activities of lysophosphatidic acid. Journal of Cellular Biochemical, 92, 1086-1094, 2004.
  37. Hasseruck, N., Erl, Tigyi, G., Ohlmann, P., Ravanat, K., Gachet, c., and Siess, W.. The plaque lipid lysophosphatidic acid stimulates platelet aggregation and platelet-monocyte aggregate formation in whole blood involvement of P2Y(1) and P2Y(12) receptors. Blood, 103, 2585-2592, 2004.
  38. Wang, D-A., Du, H., Jaggar, J.H., Brindley, D.N., Tigyi, G., and Watsky, M.A.. Expression and Characterization of SiP and LPA Receptors and LPP1 Following Rabbit Corneal Wound Healing. American Journal of Physiology - Cellular Physiology, 283, C1646-1654, 2003.
  39. Virag, T., Elrod, D., Liliom, K., Sardar, v., Yokoyama, K., Parrill, A., Miller, D., Tigyi, G.. Fatty alcohol phosphates are receptor subtype-specific mimetics and antagoinists of the LPA receptors. Molecular Pharmacology, 63, 1032-1042, 2003.
  40. Meyer zu Heringdorf, D., Vincent, M.E.M., Lipinski, M., Danneberg, K., Stropp, U., Wang, D.A., Tigyi, G., and Jakobs, K.H.,. Inhibition of calcium signaling by the sphingosine-1-phosphate receptor S1P. Cellular Signaling, 15 (4), 367-375, 2003.
  41. Rother, E., Brandi, R., Baker, D.L. Tigyi, G., and Siess, W.. Subtype-selective antagonists of lysoophosphatidic acid-receptors inhibit platelet shape change induced by mildly-oxidized LDL and plaque lipid core. Circulation, 108, 741-747, 2003.
  42. Lu, X, Cseh, S., Byun, H., Tigyi, G., and Robert Bittman. Total Synthesis of Two Photoaffinity Analogues of the Growth Factor-like Mediator Sphingsoine 1-Phosphate: Differtial Interaction with Protein Targets. Journal of Organic Chemistry, 68, 7046-7050, 2003.
  43. Tigyi, G., and Parrill, A.. Molecular Mechanisms of Lysophosphatidic Acid Action. Progress in Lipid Research, 42, 498-526, 2003.
  44. Fujiwara, Y., Sebok, A., Meakin, S., Kobayashi, T., Murakami-Murofushi, K., and Tigyi G.. The endogenous lipid mediator cyclic-phosphatidic acid mimics the actions of neurotrophins in embryonic hippocampal neurons. Journal of Neurochemistry, 87, 1272-1283, 2003.
  45. Deng, W., Wang, D.-A., Gosmanova, E., Johnson, L.R., and Tigyi, G.. Lysophosphatidic Acid Protects Intestinal Epithelial Cells from Camptothecin-Induced Apoptosis by Inhibiting the Mitochondrial Pathway. American Journal of Physiology-Liver, Gastrointestinal Physiology, 284 (5), G821-G829, 2003.
  46. Meyer zu Heringdorf, D., Liliom, K., Schafer, M., Danneberg, Jaggar, J., Tigyi, G., and Karl H. Jakobs. Photoysis of intracellular caged sphingosine-1-phosphate causes Ca(2+) mobilization independently of G protein-coupled receptors. FEBS Letts, 543, 443-449, 2003.
  47. Yue, J., Yokoyama, K., Balazs, L., Baker, D.L., Pilquil, C., Brindley, D.N., and Tigyi, G.. Mice with Transgenic Over-expression of Lipid Phosphate Phosphatase-1 Display Reproductive and Hair Growth Deficits without Alteration in Circulating Lysophosphatidate Level. Cellular Signaling, 16, 385-399, 2003.
  48. Fueller, M., Wang, D.-A., Tigyi, G., Siess, W.. Activation of Human Monocytic Cells by Lysophosphatidic Acid and Sphingosine-1-phosphate. Cellular Signalling, 5, 367-375, 2002.
  49. Nusser, N., Gosmanova, E., Zheng, Y., and Tigyi, G.. NGF signals through TrkA, P13 kinase and Rac1 to inactivate RhoA during the initiation of neuronal differentiation of PC12 cells. Journal of Biological Chemistry, 277, 35840-3584, 2002.
  50. Yokoyama, K., Baker, D.L., Virag, T., Liliom, K., Byun, H., Tigyi, G., and Bittman, R.. Sterochemical properties of lysophosphatidic acid signaling and metabolism. Biochimica et biophysica acta. International journal of biochemistry and biophysics., 1582, 296-309, 2002.