Research interests: Nutrient transport in intestine, kidney and placenta; genetic disorders of membrane transport; molecular biology of membrane transporters

Dr. Vadivel Ganapathy’s early research at the Medical College of Georgia focused on peptide transporters. It was a continuation of the graduate work he performed at the University of Madras, India. At MCG, his laboratory was involved in the cloning of two different peptide transporters, PEPT1 and PEPT2.

"We did a great deal of work in understanding the physiology and the molecular biology of that transport protein," says Dr. Ganapathy, whose laboratory has now cloned 70 different transporters from various species — more than any other laboratory in the world.

Transporters are responsible for the absorption of peptides, amino acids, sugars, vitamins and drugs. These transporters are expressed in all cell types, particularly in those tissues responsible for the absorption of nutrients (intestine and kidney).

Currently Dr. Ganapathy is studying links between cancer and transporters.

Tumor cells have an increased need for nutrients beyond that of normal cells. These nutrients cannot get into the malignant cells without transporters, he says. "So how do the cancer cells pick and choose the transporter to support that growth?"

His laboratory goal was to identify a specific transporter that tumor cells rely on for nutrients and exploit it as a drug target. Researchers found a candidate in an amino acid transporter, SLC6A14. It is a major supplier of amino acids to tumor cells but a minor one to normal cells.

"We have identified a chemical blocker of this transport system, and by blocking it you can kill the tumor cell," says Dr. Ganapathy, who is designing in vivo studies to test this approach. They must confirm that blocking SLC6A14 will not harm normal cells.

He and his team published the first paper on SLC6A14 in 2005, describing their findings relative to colon cancer. Dr. Ganapathy also sees a similar therapy benefit for patients with breast and cervical cancer where this transporter is also up-regulated.

"We think upregulation of SLC6A14 might be a general phenomenon in cancer, but we have not tested all cancers yet," he says.

Dr. Ganapathy earned his BS at the University of Madras in 1971, then followed with an MS in 1974 and a PHD in 1978 from the same institution. He has published more than 350 scholarly articles and 23 book chapters.

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Grants (selected)

• Molecular Biology of Membrane Transporters. Awarded 2002 to 2012 by Pfizer Pharmaceuticals.
• Tumor-Suppressive Function of SLC5A8 in Mammary Gland and its Relevance to Breast Cancer.  Awarded 2008 to 2013 by NIH Grant CA 131402
• SLC5A8-Mediated Switching of STAT3 from a Pro-Oncogenic Signal into a Pro-Apoptotic Signal in Breast Cancer. Awarded 2008 to 2011by DOD Grant BC 074289.

Grant information is updated quarterly.

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Publications (selected)

editorial board member:

• Pharmaceutical Research

editorial reviewer:

• American Journal of Physiology
• Metabolism
• Pediatric Research
• Journal of Receptor Research
• Biochimica et Biophysica Acta
• Placenta
• Biochemistry
• Journal of Biological Chemistry
• Journal of Physiology
• American Journal of Obstetrics and Gynecology
• Life Sciences
• FEBS Journal
• Canadian Journal of Pharmacy and Pharmacology
• Molecular Pharmacology
• Journal of Ocular Pharmacology and Therapeutics
• Molecular Pharmaceutics
• Experimental Physiology
• Current Eye Research
• Cellular and Molecular Life Sciences
• Investigative Ophthalmology and Visual Science
• Pharmaceutical Research
• Journal of Pharmacology and Experimental Therapeutics
• Physiology
• Journal of Experimental Biology
• Journal of Neurochemistry

ad hoc reviewer:

• Human Embryology and Development Study Section, National Institutes of Health
  
• British Columbia Health Care Research Foundation
• Co-chair, FASEB Summer Research Conference on “New Perspectives in Transport Biology

Chothe P, Thakkar SV, Gnana-Prakasam JP, Ananth S, Hinton DR, Kannan R, Smith SB, Martin PM, Ganapathy V. Identification of a Novel Sodium-coupled Oligopeptide Transporter (SOPT2) in Mouse and Human Retinal Pigment Epithelial Cells. Invest Ophthalmol Vis Sci. 2009 Jul 30. [Epub ahead of print.]

Thangaraju M, Karunakaran SK, Itagaki S, Gopal E, Elangovan S, Prasad PD, Ganapathy V. Transport by SLC5A8 with subsequent inhibition of histone deacetylase 1 (HDAC1) and HDAC3 underlies the antitumor activity of 3-bromopyruvate. Cancer. 2009 Jul 27. [Epub ahead of print.]

Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP, Browning DD, Mellinger JD, Smith SB, Digby GJ, Lambert NA, Prasad PD, Ganapathy V. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 2009 Apr 1;69(7):2826-32.

Martin PM, Ananth S, Cresci G, Roon P, Smith S, Ganapathy V. Expression and localization of GPR109A (PUMA-G/HM74A) mRNA and protein in mammalian retinal pigment epithelium. Mol Vis. 2009;15:362-72.

Gnana-Prakasam JP, Zhang M, Martin PM, Atherton SS, Smith SB, Ganapathy V. Expression of the iron-regulatory protein haemojuvelin in retina and its regulation during cytomegalovirus infection. Biochem J. 2009 May 1;419(3):533-43.

Ananth S, Karunakaran S, Martin PM, Nagineni CN, Hooks JJ, Smith SB, Prasad PD, Ganapathy V. Functional Identification of a Novel Transport System for Endogenous and Synthetic Opioid Peptides in the Rabbit Conjunctival Epithelial Cell Line CJVE. Pharm Res. 2009 May;26(5):1226-35.

Mysona B, Dun Y, Duplantier J, Ganapathy V, Smith SB. Effects of hyperglycemia and oxidative stress on the glutamate transporters GLAST and system xc- in mouse retinal Müller glial cells. Cell Tissue Res. 2009 Mar;335(3):477-88.

Mycielska ME, Patel A, Rizaner N, Mazurek MP, Keun H, Patel A, Ganapathy V, Djamgoz MB. Citrate transport and metabolism in mammalian cells: prostate epithelial cells and prostate cancer. Bioessays. 2009 Jan;31(1):10-20. Review.

Ganapathy V, Thangaraju M, Prasad PD. Nutrient transporters in cancer: Relevance to Warburg hypothesis and beyond. Pharmacol Ther. 2009 Jan;121(1):29-40.

Ganapathy V. A traffic signal for heterodimeric amino acid transporters to transfer from the ER to the Golgi. Biochem J. 2009 Jan 15;417(2):e9-11.

Thangaraju M, Carswell KN, Prasad PD, Ganapathy V. Colon cancer cells maintain low levels of pyruvate to avoid cell death caused by inhibition of HDAC1/HDAC3. Biochem J. 2009 Jan 1;417(1):379-89.

Thakkar SV, Miyauchi S, Prasad PD and Ganapathy V. Stimulation of Na+/Cl-coupled opioid peptide transport system in SK-N-SH cells by L-kyotorphin, an endogenous substrate for H+-coupled peptide transporter PEPT2. Drug Metab Pharmacokinet. 2008;23(4):254-62.

Umapathy NS, Dun Y, Martin PM, Duplantier JN, Roon P, Prasad PD, Smith SB, Ganapathy V. Expression and Function of System N Glutamine Transporters (SN1/SN2 or SNAT3/SNAT5) in Retinal Ganglion Cells. Invest Ophthalmol Vis Sci. 2008 Nov;49(11):5151-60.

Thangaraju M, Cresci G, Itagaki S, Mellinger J, Browning DD, Berger FG, Prasad PD, Ganapathy V. Sodium-coupled transport of the short chain fatty acid butyrate by SLC5A8 and its relevance to colon cancer. J Gastrointest Surg. 2008 Oct;12(10):1773-81; discussion 1781-2.

Anderson CM, Ganapathy V, Thwaites DT. Human solute carrier SLC6A14 is the beta-alanine carrier. J Physiol. 2008 Sep 1;586(Pt 17):4061-7.

Karunakaran S, Umapathy NS, Thangaraju M, Hatanaka T, Itagaki S, Munn DH, Prasad PD, Ganapathy V. Interaction of tryptophan derivatives with SLC6A14 (ATB0,+) reveals the potential of the transporter as a drug target for cancer chemotherapy. Biochem J. 2008 Sep 15;414(3):343-55.

Smith SB, Duplantier J, Dun Y, Mysona B, Roon P, Martin PM, Ganapathy V. In vivo protection against retinal neurodegeneration by sigma receptor 1 ligand (+)-pentazocine. Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4154-61.

Ganapathy V, Thangaraju M, Gopal E, Martin PM, Itagaki S, Miyauchi S, Prasad PD. Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. AAPS J. 2008;10(1):193-9.

Kozlowski DJ, Chen Z, Zhuang L, Fei YJ, Navarre S, Ganapathy V. Molecular characterization and expression pattern of taurine transporter in zebrafish during embryogenesis. Life Sci. 2008 May 7;82(19-20):1004-11.

Talukder JR, Kekuda R, Saha P, Prasad PD, Ganapathy V, Sundaram U. Functional characterization, localization, and molecular identification of rabbit intestinal N-amino acid transporter. Am J Physiol Gastrointest Liver Physiol. 2008 Jun;294(6):G1301-10.

Kashiwagi H, Yamazaki K, Takekuma Y, Ganapathy V, Sugawara M. Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation. Amino Acids. 2009 Feb;36(2):219-30.

Kwon IK, Schoenlein PV, Delk J, Liu K, Thangaraju M, Dulin NO, Ganapathy V, Berger FG, Browning DD. Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis. Cancer. 2008 Apr 1;112(7):1462-70.

Metzner L, Natho K, Zebisch K, Dorn M, Bosse-Doenecke E, Ganapathy V, Brandsch M. Mutational analysis of histidine residues in the human proton-coupled amino acid transporter PAT1. Biochim Biophys Acta. 2008 Apr;1778(4):1042-50.

Gnana-Prakasam JP, Martin PM, Mysona BA, Roon P, Smith SB, Ganapathy V. Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/Toll-like receptor-4 pathway independent of Hfe.Biochem J. 2008 Apr 1;411(1):79-88.

Dun Y, Duplantier J, Roon P, Martin PM, Ganapathy V, Smith SB. Serine racemase expression and D-serine content are developmentally regulated in neuronal ganglion cells of the retina. J Neurochem. 2008 Feb;104(4):970-8.

Umapathy NS, Gnana-Prakasam JP, Martin PM, Mysona B, Dun Y, Smith SB, Ganapathy V, Prasad PD. Cloning and functional characterization of the proton-coupled electrogenic folate transporter and analysis of its expression in retinal cell types.Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5299-305.

Dun Y, Thangaraju M, Prasad P, Ganapathy V, Smith SB. Prevention of excitotoxicity in primary retinal ganglion cells by (+)-pentazocine, a sigma receptor-1 specific ligand. Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4785-94.

Shekhawat PS, Srinivas SR, Matern D, Bennett MJ, Boriack R, George V, Xu H, Prasad PD, Roon P, Ganapathy V. Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) mice. Mol Genet Metab. 2007 Dec;92(4):315-24.

Yang D, Thangaraju M, Browning DD, Dong Z, Korchin B, Lev DC, Ganapathy V, Liu K. IFN regulatory factor 8 mediates apoptosis in nonhemopoietic tumor cells via regulation of Fas expression. J Immunol. 2007 Oct 1;179(7):4775-82.

Srinivas SR, Prasad PD, Umapathy NS, Ganapathy V, Shekhawat PS. Transport of butyryl-L-carnitine, a potential prodrug, via the carnitine transporter OCTN2 and the amino acid transporter ATB(0,+). Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1046-53.

Deuther-Conrad W, Patt JT, Lockman PR, Allen DD, Patt M, Schildan A, Ganapathy V, Steinbach J, Sabri O, Brust P. Norchloro-fluoro-homoepibatidine (NCFHEB) - a promising radioligand for neuroimaging nicotinic acetylcholine receptors with PET. Eur Neuropsychopharmacol. 2008 Mar;18(3):222-9.

Gopal E, Umapathy NS, Martin PM, Ananth S, Gnana-Prakasam JP, Becker H, Wagner CA, Ganapathy V, Prasad PD. Cloning and functional characterization of human SMCT2 (SLC5A12) and expression pattern of the transporter in kidney. Biochim Biophys Acta. 2007 Nov;1768(11):2690-7.

Schoenlein PV, Hou M, Samaddar JS, Gaddy VT, Thangaraju M, Lewis J, Johnson M, Ganapathy V, Kallab A, Barrett JT. Downregulation of retinoblastoma protein is involved in the enhanced cytotoxicity of 4-hydroxytamoxifen plus mifepristone combination therapy versus antiestrogen monotherapy of human breast cancer. Int J Oncol. 2007 Sep;31(3):643-55.

Martin PM, Dun Y, Mysona B, Ananth S, Roon P, Smith SB, Ganapathy V. Expression of the sodium-coupled monocarboxylate transporters SMCT1 (SLC5A8) and SMCT2 (SLC5A12) in retina.Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3356-63.

Baisden B, Sonne S, Joshi RM, Ganapathy V, Shekhawat PS. Antenatal dexamethasone treatment leads to changes in gene expression in a murine late placenta. Placenta. 2007 Oct;28(10):1082-90.

Takekuma Y, Kakiuchi H, Yamazaki K, Miyauchi S, Kikukawa T, Kamo N, Ganapathy V, Sugawara M. Difference between pharmacokinetics of mycophenolic acid (MPA) in rats and that in humans is caused by different affinities of MRP2 to a glucuronized form. J Pharm Pharm Sci. 2007;10(1):71-85.

Yang D, Thangaraju M, Greeneltch K, Browning DD, Schoenlein PV, Tamura T, Ozato K, Ganapathy V, Abrams SI, Liu K. Repression of IFN regulatory factor 8 by DNA methylation is a molecular determinant of apoptotic resistance and metastatic phenotype in metastatic tumor cells.Cancer Res. 2007 Apr 1;67(7):3301-9.

Makrides V, Bauer R, Weber W, Wester HJ, Fischer S, Hinz R, Huggel K, Opfermann T, Herzau M, Ganapathy V, Verrey F, Brust P. Preferred transport of O-(2-[18F]fluoroethyl)-D-tyrosine (D-FET) into the porcine brain. Brain Res. 2007 May 25;1147:25-33.

Miyauchi S, Gopal E, Thakkar SV, Ichikawa S, Prasad PD, Ganapathy V. Differential modulation of sodium- and chloride-dependent opioid peptide transport system by small nonopioid peptides and free amino acids. J Pharmacol Exp Ther. 2007 Apr;321(1):257-64.

Gopal E, Miyauchi S, Martin PM, Ananth S, Roon P, Smith SB, Ganapathy V. Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract. Pharm Res. 2007 Mar;24(3):575-84.

Seki A, Miyauchi S, Hayashi S, Kikukawa T, Kubo M, Demura M, Ganapathy V, Kamo N. Heterologous expression of Pharaonis halorhodopsin in Xenopus laevis oocytes and electrophysiological characterization of its light-driven Cl-pump activity. Biophys J. 2007 Apr 1;92(7):2559-69.

Dun Y, Mysona B, Itagaki S, Martin-Studdard A, Ganapathy V, Smith SB. Functional and molecular analysis of D-serine transport in retinal Müller cells. Exp Eye Res. 2007 Jan;84(1):191-9.

Gopal E, Miyauchi S, Martin PM, Ananth S, Srinivas SR, Smith SB, Prasad PD, Ganapathy V. Expression and functional features of NaCT, a sodium-coupled citrate transporter, in human and rat livers and cell lines. Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G402-8.

Publications are updated quarterly. For a complete listing, see Dr. Ganapathy's work on PubMed.

Books and book chapters

• Smith CH, Moe AJ and Ganapathy V. (1992) Nutrient transport pathways across the epithelium of the placenta. Annual Review of Nutrition 12:183-206.
• Ganapathy V, Brandsch M and Leibach H. (1994) Intestinal transport of amino acids and peptides. In: Physiology of the Gastrointestinal Tract (ed. Johnson LR), 3rd edition, pp. 1773-1794. Raven Press, New York.
• Ganapathy V, Brandsch M and Leibach FH. (1994) Proton-coupled peptide transport in the small intestine and kidney. In: Molecular and Cellular Mechanisms of H+ Transport (ed. Hirst BH), NATO ASI Series, Vol. 89, pp. 275-282. Springer-Verlag, Heidelberg, Germany.
• Ganapathy V and Leibach FH. (1994) Expression and regulation of the taurine transporter in cultured cell lines of human origin. In: Taurine in Health and Disease (eds. Huxtable RJ and Michalk D). Advances in Experimental Medicine and Biology, volume 359, pp. 51-57. Plenum Press, New York.
• Ganapathy V and Leibach FH. (1995) Placental biogenic amines and their transporters. In: Placental Toxicology (ed. Ramasastry BV), Vol, I, pp. 161-174. CRC Press, Boca Raton, Fla.
• Brandsch M, Ganapathy V and Leibach FH (1995) Role of dipeptidyl¬peptidase IV (DP IV) in intestinal and renal absorption of peptides. In: CD26-Dipeptidylpeptidase IV (ed. Fleischer B), pp. 111-129. CRC Press, Boca Raton, Fla.
• Ganapathy V, Prasad PD and Leibach FH (1996) Uptake measurements of thyroid hormones and amino acids in cultured cells. In: Endocrine Methods (ed. Thomas JA), pp. 187-202. Academic Press, San Diego, Calif.
• Leibach FH and Ganapathy V (1996) Peptide transporters in the intestine and the kidney. Annual Review of Nutrition 16: 99-119.
• Fei YJ, Ganapathy V and Leibach FH. (1998) Molecular and structural features of the proton-coupled oligopeptide transporter superfamily. Progress in Nucleic Acid Research and Molecular Biology 58: 239-261.
• Ganapathy V, Prasad PD and Leibach FH. (1998) Use of human placenta in studies of monoamine transporters. Methods in Enzymology 296: 278-290.
• Ganapathy V and Leibach FH. (1999) Protein digestion and assimilation. In: Textbook of Gastroenterology (ed. Yamada T), 3rd edition, pp. 456-467. Lippincott Williams & Wilkins, Philadelphia.
• Ganapathy V, Prasad PD, Ganapathy ME and Leibach FH. (1999) Drugs of abuse and placental transport. In: Advanced Drug Delivery Reviews: Transplacental Drug Delivery (ed. Audus KL). 38: 99-110. Elsevier.
• Ganapathy V, Prasad PD and Leibach FH. (1999) Choriocarcinoma. In: Human Cell Culture (eds. Masters, JRW and Palsson B), vol. II, pp. 141-147. Kluwer Academic Publishers.
• Ganapathy V, Ganapathy ME and Leibach FH. (2001) Intestinal transport of peptides and amino acids. In: Current Topics in Membranes (eds. Barrett KE and Donowitz M), vol. 50, pp 379-412. Academic Press.
• Ganapathy V, Ganapathy ME and Leibach FH. (2003) Protein digestion and assimilation. In: Textbook of Gastroenterology (ed. Yamada T), 4th edition, pp. 438-448. Lippincott Williams & Wilkins, Philadelphia.
• Ganapathy V, Inoue K, Prasad PD and Ganapathy, ME. (2004) Cellular uptake of amino acids: system and regulation. In: Metabolic and Therapeutic Aspects of Amino Acids in Clinical Nutrition (ed. Cynober LA), 2nd edition, pp. 63-78. CRC Press, Boca Raton, Fla.
• Prasad PD, Jones CB and Ganapathy V. (2005) Placenta as a nutritional unit. In: Perinatal Nutrition: Optimizing Infant Health and Development (ed. Bhatia J), pp. 77-110. Marcel Dekker, Inc., New York.
• Ganapathy V, Gupta N and Martindale RG. (2006) Protein digestion and absorption. In: Physiology of the Gastrointestinal Tract (ed. Johnson LR), 4th Edition, pp. 1667-1692. Raven Press, New York.
• Ganapathy V, Fei YJ, and Prasad PD. (2006) Heterologous expression systems for studying placental transporters. In: Methods in Molecular Medicine, Vol. 122: Placenta and Trophoblast: Methods and Protocols (eds. Soares MJ and Hunt JS), Vol. 2, pp. 285-300. The Humana Press Inc., Totowa, New Jersey.
• Ganapathy V and Fujita T. (2006) Identity of the high-affinity sodium/carboxylate cotransporter NaC3 as the N-acetyl-L-aspartate transporter. In: N-Acetylaspartate. A Unique Neuronal Molecule in the Central Nervous System. Advances in Experimental Medicine and Biology (eds. Moffett JR, Tieman SB, Weinberger DR, Coyle JT and Namboodiri AMA), Vol. 576, pp. 67-76. Springer, New York.
• Ganapathy V, Ganapathy ME and Inoue K. (2007) Cloning of sigma-1 receptor and structural analysis of its gene and promoter region. In: Sigma Receptors: Chemistry, Cell Biology, and Clinical Implications (eds. Matsumoto RR, Bowen WD and Su TP), pp. 99-112. Springer, New York.
• Ganapathy V, Ananth S, Smith SB and Martin PM. (2007) Vitamin C transporters in the retina. In: Ocular Transporters in Diseases and Drug Delivery (eds. Tombran-Tink J and Barnstable CJ), pp. 421-434. The Human Press, Totowa, New Jersey.
• Ganapathy V, Ganapathy ME and Leibach FH. (2008) Protein digestion and assimilation. In: Textbook of Gastroenterology (eds. Yamada T, Alpers DH, Kalloo, AN, Kaplowitz N, Owyang C and Powell DW) 5th edition, pp. 464-477. Blackwell Publishing.
  

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Affiliations

• Professor, Obstetrics and Gynecology, Physiology, Graduate Studies, Biochemistry and Molecular Biology, Medical College of Georgia
• Member, American Society of Biochemistry and Molecular Biology
• Member, American Physiological Society
• Member, Association of Medical and Graduate Departments of Biochemistry
• Member, Association for Research in Vision and Ophthalmology
• Member, International Federation of Placenta Associations

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