Gabor J. Tigyi, PhD
Harriet Van Vleet Endowment Professor, UTHSC
Professor of Physiology and Chemistry, University of Memphis
Harriet S. Van Vleet Chair in Oncology Research
Associate Director for Basic Science UT Cancer Institute
Professor, (adjunct) School of Graduate Sciences, Hokkaido University, Japan
Phone: 901.448.4793
Fax: 901.448.7126
gtigyi@physio1.uthsc.edu
Education
MD, 1982 Medical University of Pecs, Hungary
PhD, 1992 Hungary Academy of Sciences, Budapest
Research Interest
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.
Honors
- Member, Academie Europeene Des Sciences, Des Art at Des Lettres, Paris, France, 2007
- Keynote Speaker, University of Tokyo 21st Century COE symposium “Drug discovery and Chemical biology”, 2006
- Keynote Speaker, FASEB Summer Conference on Lysophospholipids, 2005
- Foreign Member of the Hungarian Academy of Sciences, 2004
- Takeda Foundation Lecturer, 2001
- Established Investigator of the American Heart Association, 1997-2000.
Editorial Boards
- Journal of Biological Chemistry
- Biochimica and Biophysica Acta
- Guest Editor, J. Cellular Biochemistry
- Guest Editor, BBA Special Issue on Lysophospholipids 2004 and 2008
- Chair, 2003, Co-Chair, 2001, FASEB Summer Conference on Lysolipids and Related Bioactive Mediators in Biology and Diseases 2000
- IUPHAR Nomenclature Committee on Lysolipid Receptors
Research Support
NIH R01 HL 079004 Tigyi (PI)
Analysis of LPA Signaling through the GPCR-PPARg axis
Major goals of project: To understand the role of LPA GPCR and PPARgamma receptors
in neointima formation.
Role: PI
NIH R01 HL 061469 Tigyi (PI)
Therapeutically promising phospholipid growth factors
The goal of this project was to isolate and characterize a novel group of naturally
occurring lipids, now known as the phospholipids growth factor (PLGF) family, and
to investigate the structure-activity
relationship of the PLGF receptors (PLGFR).
Role: PI
NIH R01 CA 092160 Tigyi (PI)
Ligand recognition by phospholipid growth factor receptors
The goals of this project was to develop and validate a refined computational model
for the interaction of SPP with the EDG1 receptor, identify residues conferring specificity
for sphingolipids in the EDG3/5/6/8 receptor subfamily, and to identify residues involved
in glycerolipid recognition in the EDG2/4/7 receptor subfamily
Role: PI
USAMRMC Proposal Number 06171001 Tigyi (PI)
Novel Methods for Imaging PET Biomarkers and Gene Therapy of Cancer
The objective of this proposal is to set up two core laboratories at the university
of Tennessee Health Science Center for Viral Vector Core and Microfluidic Chemistry
services.
Role: PI
NIH R01 HL 084007 Parrill (PI)
Computational Approach to Ligand Discovery for LPA GPCR and PPAR.
The goal of this project is to elucidate the structure of the extracellular loops
of lysophospholipid receptors .
Role: Co-PI
NIH RO3 AI 0170942 Naren (PI)
V. cholerae as a bioterror agent: New means of treating a potential pandemic
Goals: The aims of this grant proposal are to test if foods rich in LPA will inhibit
CTX-induced diarrhea in mice. And to test if metabolically stabilized synthetic LPA-receptor
agonists exhibit potent anti-diarrheal properties (compared to LPA).
Role: Collaborator
AI 078514 Tigyi (PI)
NIH/NIAID
Development of a Novel Gastrointestinal Radiomitigator
The main objective of this grant is to determine the therapeutic efficacy of octadecenyl
thiophosphate, a novel radiomitigator using mouse and non-human primates of radiation-induced
mucositis.
Role: PI
Selected Publications
Book Chapters
- Tigyi, G. Antibody production with hybridomas. In: Molecular Methods in Immunology, edited by F. Antoni and P. Zavodszky. Budapest: Medicina Press, 1987.
- Dyer, D., Tigyi, G., and Miledi, R. Neurite retraction and suppression of early responses to nerve growth factor in PC12 cells by a serum protein. In: Proceedings of the Miami Bio/Technology Winter Symposium, edited by R.L. Rotundo et al. Oxford/Washington: IRL Press, 1989, p. 81.
- Tigyi, G., and Miledi, R. Isolation and characterization of a novel serum factor that stimulates the phosphoinositide-Ca2+ signaling system. In: Proceedings of the Third International Regeneration Symposium, Neurology and Neurobiology Series, edited by F. J. Seil. New York: Alan R. Liss, 1989.
- Dyer, D., Tigyi, G., and Miledi, R. Antimitogenic and neurite retraction effects caused by a serum factor that stimulates the phosphoinositide- Ca2+ signaling system. In: Proceedings of the Third International Regeneration Symposium, Neurology and Neurobiology Series, edited by F. J. Seil. New York: Alan R. Liss, 1989.
- Tigyi, G., Fischer, D.J. Liliom, K., Guo, Z., Virág, T., Sun, G, Miller, D.D., Murakami-Murofushi, K. Kobayashi, S., and Erickson, J.R. Determinants of receptor subtype specificity in the LPA-like lipid mediator family. In: Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Related Diseases, edited by K.V. Honn, S. Nigam, L.J. Marnett, and E. Dennis. New York/London/Washington, DC/Boston, 1998.
- Tigyi, G., Liliom, K., Fischer, D.J., and Guo, Z. Phospholipid growth factors: identification and mechanism of action. In: Lipid Second Messengers, edited by R. Rubin and S. Laychock. CRC Press, pp. 51-81, 1998.
- Goetzl, E.J., Lee, H., and Tigyi, G. Lysophosholipid growth factors. Cytokine reference.:/ Academic Press. New York/London, pp. 1407-1418, 2000.
- Tigyi, G. Lysophosphatidate and sphingosine 1-phosphate receptors. In: Encyclopedia of Biological Chemistry, edited by W.J. Lennarz and M.D. Lane. Elsevier, pp. 602-604, 2005.
- Dopico, A., and Tigyi, G. Lipid species and membrane composition., edited by A. Dopico. Humana Press, 2007.
- Valentine, W.J., and Tigyi, G.High throughput assays to measure intracellular Ca2+ mobilization in cells that express recombinant S1P receptor subtypes. Meth. Mol. Biol. 874: 77-87, 2012. PMID: 22528441.
Selected Journal Citations
- Lehman, M., A. Fournier, I. Selles-Navarro, P. Dergham, N. Leclerc, Tigyi, G., and L. McKerracher. Inactivation of Rho signaling pathway promotes CNS axon regeneration J. Neurosci. 19: 7537-7547, 1999.
- Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S, Tigyi G. (2002) International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature. Pharmacol Rev. 54:265-269.
- Tigyi, G., and Miledi, R. (1992) Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus oocytes and neurite retraction in PC12 pheochromocytoma cells. J. Biol. Chem. 267: 21360-21367, 1992.
- Siess, W., K. J. Zangl, M. Essler, M. Bauer, R. Brandl, C. Corrinth, R. Bittman, Tigyi, G., and M. Aepfelbacher, M. Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly-oxidized LDL and accumulates in human atherosclerotic lesions. Proc. Natl. Acad. Sci. USA 96: 6931-6936, 1999.
- Guo, Z., Liliom, K., D. J. Fischer, I. C. Bathurst, D. J. Tomei, M. C. Kiefer, and Tigyi, G. Molecular cloning of a high affinity receptor for the growth factor-like phospholipid mediator lysophosphatidic acid. Proc. Natl. Acad. Sci. USA 93: 14367-14372, 1996.
- Sano,S., Baker, D., Wada, A. Yatomi, Y., Kobayashi, T., Igarashi, Y., Tigyi, G. (2002) Multiple Mechanisms Linked to Platelet Activation Result in Lysophosphatidic Acid and Sphingosine-1-Phosphate Generation in Blood. J. Biol. Chem 277:21197-21206.
- Leitinger, N., T. R. Tyner, L. Oslund, C. Rizza, G. Subbanagounder, H. Lee, P. T. Shih, N. Mackman, Tigyi, G., M. C. Territo, J. A. Berliner, and D. K. Vora. Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proc. Natl. Acad. Sci, USA 96:12010-12015, 1999.
- Tigyi, G., Fischer, D., Yang, C., Dyer, D,, Sebök, A., and Miledi, R. Lysophosphatidic acid-induced neurite retraction in PC12 cells: control by phosphoinositide-Ca2+ signaling and Rho. J. Neurochem. 66: 537-548,
- Jo, E, Sanna, M.G., Gonzalez-Caberra, P.J., Thangada, S., Tigyi, G., Osborne, D.A., Hla, T., Parrill, A.L., Rosen, H. (2005) S1P1-selective in vivo-active agonists from high throughput screening: Off the shelf chemical probes of receptor interactions, signaling and fate. Chem. Biol. Cell Press. 12:703-15.
- Yatomi, Y., T. Ohmori, G. Rile, F. Kazama, H. OkamotoT., Sano, K. Satoh, S. Kume, Tigyi, G., Y.Igarashi, and Y. Ozaki. Sphingosine 1-phosphate as a major bioactive lysophospholipid which is released from platelets and interacts with endothelial cells. Blood 96: 3431-3438, 2000.