Augusta University Cancer Center
Vadivel Ganapathy, PhD
Developmental Therapeutics; Multidisciplinary Gastrointestinal,
Gynecologic Oncology Teams; Molecular Biologist
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.
Address: CB 2740B
College of Graduate Studies
1120 15th Street
Augusta, GA 30912
Office: (706) 721-7652
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.
Grant information is updated quarterly.
editorial board member:
Edwards N, Anderson CM, Gatfield KM, Jevons MP, Ganapathy V, Thwaites DT. Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2). Biochim Biophys Acta. 2011 Jan;1808(1):260-70.
Ha Y, Dun Y, Thangaraju M, Duplantier JN, Dong Z, Liu K, Ganapathy V, Smith SB. Sigma receptor 1 modulates ER stress in retinal neurons. Invest Ophthalmol Vis Sci. 2011 Jan 25;52(1):527-40. Print 2011.
Zimmerman M, Yang D, Hu X, Liu F, Singh N, Browning D, Ganapathy V, Chandler P, Choubey D, Abrams SI, Liu K. IFN-γ upregulates survivin and Ifi202 expression to induce survival and proliferation of tumor-specific T cells. PLoS One. 2010 Nov 22;5(11):e14076.
Ganapathy V. Drugs of abuse and human placenta. Life Sci. 2010 Oct 15. [Epub ahead of print]
Li Y, Zhang M, Chen H, Dong Z, Ganapathy V, Thangaraju M, Huang S. Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. Cancer Res. 2010 Oct 15;70(20):7894-904.
Kommareddi PK, Nair TS, Thang LV, Galano MM, Babu E, Ganapathy V, Kanazawa T, McHugh JB, Carey TE. Isoforms, expression, glycosylation, and tissue distribution of CTL2/SLC44A2. Protein J. 2010 Aug;29(6):417-26.
Singh N, Thangaraju M, Prasad PD, Martin PM, Lambert NA, Boettger T, Offermanns S, Ganapathy V. Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J Biol Chem. 2010 Sep 3;285(36):27601-8.
Fan X, Ross DD, Arakawa H, Ganapathy V, Tamai I, Nakanishi T. Impact of system L amino acid transporter 1 (LAT1) on proliferation of human ovarian cancer cells: a possible target for combination therapy with anti-proliferative aminopeptidase inhibitors. Biochem Pharmacol. 2010 Sep 15;80(6):811-8.
Bozard BR, Ganapathy P, Duplantier JN, Mysona B, Ha Y, Roon P, Smith R, Goldman ID, Prasad PD, Martin PM, Ganapathy V, Smith SB. Molecular and biochemical characterization of folate transport proteins in retinal Muller cells. Invest Ophthalmol Vis Sci. 2010 Jun;51(6):3226-35.
Ganapathy V, Ge R, Grazioli A, Xie W, Banach-Petrosky W, Kang Y, Lonning S, McPherson J, Yingling JM, Biswas S, Mundy GR, Reiss M. Targeting the Transforming Growth Factor-beta pathway inhibits human basal-like breast cancer metastasis. Mol Cancer. 2010 May 26;9:122.
Mazurek MP, Prasad PD, Gopal E, Fraser SP, Bolt L, Rizaner N, Palmer CP, Foster CS, Palmieri F, Ganapathy V, St hmer W, Djamgoz MB, Mycielska ME. Molecular origin of plasma membrane citrate transporter in human prostate epithelial cells. EMBO Rep. 2010 Jun;11(6):431-7. Epub 2010 May 7.
Gnana-Prakasam JP, Martin PM, Smith SB, Ganapathy V. Expression and function of iron-regulatory proteins in retina. IUBMB Life. 2010 May;62(5):363-70. Review.
Becker HM, Mohebbi N, Perna A, Ganapathy V, Capasso G, Wagner CA. Localization of members of MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis. Am J Physiol Renal Physiol. 2010 Jul;299(1):F141-54.
Kwon IK, Wang R, Thangaraju M, Shuang H, Liu K, Dashwood R, Dulin N, Ganapathy V, Browning DD. PKG inhibits TCF signaling in colon cancer cells by blocking beta-catenin expression and activating FOXO4. Oncogene. 2010 Jun 10;29(23):3423-34.
Miyauchi S, Gopal E, Babu E, Srinivas SR, Kubo Y, Umapathy NS, Thakkar SV, Ganapathy V, Prasad PD. Sodium-coupled electrogenic transport of pyroglutamate (5-oxoproline) via SLC5A8, a monocarboxylate transporter. Biochim Biophys Acta. 2010 Jun;1798(6):1164-71.
Ananth S, Zhuang L, Gopal E, Itagaki S, Ellappan B, Smith SB, Ganapathy V, Martin P. Diclofenac-induced stimulation of SMCT1 (SLC5A8) in a heterologous expression system: a RPE specific phenomenon. Biochem Biophys Res Commun. 2010 Mar 26;394(1):75-80.
Cresci GA, Thangaraju M, Mellinger JD, Liu K, Ganapathy V. Focus on the Butyrate Receptor GPR109A and the Butyrate Transporter SLC5A8. J Gastrointest Surg. 2010 Mar;14(3):449-61.
Cresci GA, Thangaraju M, Mellinger JD, Liu K, Ganapathy V. Colonic Gene Expression in Conventional and Germ-Free Mice with a Focus on the Butyrate Receptor GPR109A and the Butyrate Transporter SLC5A8. J Gastrointest Surg. 2010 Mar;14(3):449-61.
Periyasamy-Thandavan S, Jackson WH, Samaddar JS, Erickson B, Barrett JR, Raney L, Gopal E, Ganapathy V, Hill WD, Bhalla KN, Schoenlein PV. Bortezomib blocks the catabolic process of autophagy via a cathepsin-dependent mechanism, affects endoplasmic reticulum stress and induces caspase-dependent cell death in antiestrogen-sensitive and resistant ER(+) breast cancer cells. Autophagy. 2010 Jan 12;6(1).
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. 2010 Jan;51(1):413-20.
Anderson CM, Jevons M, Thangaraju M, Edwards N, Conlon NJ, Woods S, Ganapathy V, Thwaites DT. Transport of the
photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine. J Pharmacol Exp Ther. 2010 Jan;332(1):220-8.
Gnana-Prakasam JP, Thangaraju M, Liu K, Ha Y, Martin PM, Smith SB, Ganapathy V. Absence of iron-regulatory protein Hfe results in hyperproliferation of retinal pigment epithelium: role of cystine/glutamate exchanger. Biochem J. 2009 Nov 11;424(2):243-52.
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 Oct 15;115(20):4655-66.
Tachikawa M, Kasai Y, Yokoyama R, Fujinawa J, Ganapathy V, Terasaki T, Hosoya K. The blood-brain barrier transport and cerebral distribution of guanidinoacetate in rats: involvement of creatine and taurine transporters. J Neurochem. 2009 Oct;111(2):499-509.
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.
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.
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.
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.
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.
Publications are updated quarterly. For a complete listing, see Dr. Ganapathy's work on PubMed.
Books and book chapters