2006–2013SENIOR SCIENTIST,INFLAMMATION DISCOVERY &BIOCHEMICAL PHARMACOLOGY
Focus: Major depressionand respiratory disease areas
- Provided pharmacology leadership for advancing three clinical candidates to first–in human studies in depression and respiratory disease therapeutic areasProvided team leadership for in vitro pharmacology studies for multiple researchprojects and enabled research teamsto achievelead selection, lead optimization and clinical candidate selection milestones
- Contributed widely to pharmacology studiestargeting receptors, transporters and ion channelsManaged research activities performed through CROsand due diligence of in–licensing projects
- Facilitated IND submissions by providing pharmacology data reports and interpretation
- Received Roche Pharmaceuticals Research Award for implementing new assay protocols that doubled team productivity and reduced assay cost by 50%
UNIVERSITY OF KENTUCKY,
LEXINGTON,KY2000–2006ASSISTANT PROFESSOR,ANATOMY &NEUROBIOLOGY,COLLEGE OF MEDICINE
Focus: Regulation of brain cholinergic and monoaminergic pathwayswith relevance to Alzheimer’s disease, Parkinson’s disease and major depression
- Secured and managed $1million in research fundingto study cholineand monoaminetransporter function and regulation
- Developedand managed research projects involving pharmacological and neurochemical assays in vivo and in vitro
- Directed doctoral and master level research work and enabled graduation of 1 Ph.D.and3M.S. candidates
- Obtained National Alliance for Research in Schizophrenia and Depression Young Investigator Award
- Received the University of Kentucky Wethington Research Awards, 4 consecutive years
- Innovation in Pharma, MBA Accelerated Certificate Course, Rutgers University, Newark, New Jersey(2012)
- Post–doctoral training in Neuroscience & Pharmacology, Vanderbilt University, Nashville, Tennessee(1995–1998)
- Ph.D. in Pharmacology, University of Houston, Houston, Texas(1995)
- M.S. in Pharmacology, L.M. College of Pharmacy, Gujarat University, India (1988)
- B.S.in Pharmaceutical Sciences, Madras Medical College, University of Madras, India (1986)
SELECTED RESEARCH PUBLICATIONS
1.Cheng DT, Ma C, Niewoehner J, Dahl M, Tsai A, Zhang J, Gonsiorek W,Apparsundaram S, Pashine A, Ravindran P, Jung J, Hang J, Allard J, Bitter H, Tribouley C, Narula S, Wilson S, Fuentes ME.Thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma.J Allergy Clin Immunol. 2013;132:455–62.
2.Tang X, Peng R, Phillips JE, Deguzman J, Ren Y,Apparsundaram S, LuoQ, Bauer CM, Fuentes ME, Demartino JA, Tyagi G, Garrido R, Hogaboam CM, Denton CP, Holmes AM, Kitson C, Stevenson CS, Budd DC. Assessment of Brd4 Inhibition in Idiopathic Pulmonary Fibrosis Lung Fibroblasts and inVivo Models of Lung Fibrosis.Am J Pathol. 2013;183:470–9.
3.Chen G, Panicker S, Lau K–Y, Apparsundaram S, Patel VA, Chen S–L, Soto R, Jung JKC, Ravindran P, Okuhara D, Bohnert G, Che Q, Rao PE, Allard JD, Badi L, Bitter H–M, Nunn PA, Narula SK, DeMartino JA. Characterization of novel CRAC inhibitor that potently blocks human T cell activation and effector functions. Mol. Immunol; 2013; 54: 355–367.
4.Tang X, Peng R, Ren Y,ApparsundaramS, Deguzman J, Bauer CM, Hoffman AF, HamiltonS, Liang Z, Zeng H, Fuentes ME, Demartino JA, Kitson C, Stevenson CS, Budd DC. BETbromodomainproteinsmediatedownstreamsignalingeventsfollowinggrowthfactorstimulationinhumanlungfibroblastsandareinvolvedinbleomycin–inducedpulmonaryfibrosis.Mol.Pharmacol. 2013; 83:283–293.
5.Ren Y, Guo L, Tang X,ApparsundaramS, Kitson C, Deguzman J, Fuentes ME, Coyle L, Majmudar R, Allard J, Truitt T, Hamid R, Chen Y, Qian Y, Budd DC.Comparing the differential effects of LPA on the barrier function of human pulmonary endothelial cells. Microvasc.Res.2013; 85:59–67.
6.Liu X, Vilenski O, Kwan J, Apparsundaram Sand Weikert R. Unbound brain concentration determines receptor occupancy: a correlation of drug concentration and brain serotonin and dopamine reuptake transporter occupancy for eighteen compounds in rats. Drug Met.Disp.2009; 37:1548–1556.
7.Zhu J, Apparsundaram S and Dwoskin LP. Nicotinic receptor activation increases [3H]dopamine uptake and cell surface expression of dopamine transporters in rat prefrontal cortex J. Pharmacol. Exp. Ther. 2009; 328:931–939
8.Apparsundaram S, Stockdale DJ, HenningsenRA, Milla ME, Martin RS. Antidepressants targeting the serotonin reuptake transporter (SERT) act via a competitive mechanism.J.Pharmacol.Exp.Ther.2008; 327:982–990
9.Martin RS, Henningsen RA, Suen A, Apparsundaram S, Leung B, Jia Zhongjiang, Kondru RK and Milla ME.Kinetic and thermodynamic assessment of binding of serotonin transporter inhibitors.J.Pharmacol.Exp.Ther.2008; 327:991–1000
10.Middleton LS, Apparsundaram S, King–Pospisil KA, Dwoskin LP. Nicotine increases dopamine transporter function in rat striatum through a trafficking–independent mechanism. Eur J Pharmacol 2007; 554:128–136.
11.Apparsundaram SThe norepinephrine transporter and regulation of synaptic transmission. Ordway GA, Swartz MA and Frazer A, editors. Brain Norepinephrine: Neurobiology and Therapeutics, Cambridge: Cambridge University;2007. 119–155 pp.Nickell J, Salvatore MF, Pomerleau F, Apparsundaram S, Gerhardt GA. Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum. Neurobiol Aging 2007; 28: 1737–1748.
12.Parikh V, Apparsundaram S, Kozak R, Richards JB, Sarter M. Reduced expression and capacity of striatal high–affinity choline transporter in hyperdopaminergic mice. Neuroscience2006; 141:379–389.
13.Apparsundaram S, Martinez V, Parikh V, Kozak R, Sarter M.Increased capacity and density of choline transporters situatedin synaptic membranes of the right medial prefrontal cortex of attentional task–performing rats. J. Neurosci. 2005; 25:3851–385.
14.Zhu J, Apparsundaram S, Bardo M, Dwoskin L.Environmental enrichment reduces dopamine transporter function and cell surface expression in the rat medial prefrontal cortex. J. Neurochem. 2005; 93:1434–1443.
15.Akers WS, Shah SK, Flynn JD and Apparsundaram S. Effect of clonidine on cardiac norepinephrine spillover in isolated rat heart. J. Cardiovasc. Pharmacol. 2004; 43:830–838.
16.Gates J, Ferguson SM, Blakely RD and Apparsundaram S.Regulation of presynaptic choline transporter phosphorylation and surface expression by protein kinase C and protein phosphatase 1/2A..J. Pharmacol. Exp. Ther. 2004; 310:536–545.
17.Zhang L, Fletcher–Turner A, Marchionni MA, Apparsundaram S, Lundgren KH, Yurek DM, Seroogy KB. Neurotrophic and neuroprotective effects of the neuregulin glial growth factor–2 on dopaminergic neurons in rat primary midbrain cultures. J. Neurochem.2004; 91:1358–1368.
18.Sung U,Apparsundaram S, Galli A, Kahlig KM, Savchenko V, Schroeter S, Quick M and Blakely RD.A regulated interaction of syntaxin 1A with the antidepressant–sensitive norepinephrine transporter establishes catecholamine clearance capacity. J. Neurosci. 2003; 23:1697–1709.
19.Salvatore MF, Apparsundaram Sand Gerhardt GA. Decreased plasma membrane expression of the striatal dopamine transporter in aging. Neurobiology of Aging 2003; 24: 1147–1154.
20.Ferguson SM, Valentina S, Apparsundaram S, Zwick M, Wright J, Levey AI, Heilman, CJ, Yi H, Levey AI and Blakely RD.Vesicular localization and activity–dependent trafficking of presynaptic choline transporters. J. Neurosci.2003; 23:9697–9709.
21.Partridge JG, Apparsundaram S, Gerhardt GA, Ronesi J and Lovinger DM. Nicotinicacetylcholine receptors interact with dopamine in induction of striatal long–term depression. J.Neurosci.2002; 22:2541–2549
22.Apparsundaram S, Sung U, Price R and Blakely RD. Trafficking–dependent and independent pathways of neurotransmitter transporterregulation differentially involving p38 MAP kinase revealed in studies of insulin modulation of norepinephrine transport in SK–N–SH cells. J. Pharmacol. Exp. Ther.2001; 299:666–677.
23.Apparsundaram S, Ferguson SM and Blakely RD.Molecular cloning and characterization of a murine, hemicholinium–3–sensitive transporter. Biochemical Society Transactions 2001; 29: 711–716.
24.Apparsundaram S. Function and regulation of monoamine transporters: Focus on the norepinephrine transporter. CNS Spectrum 2001; 6:671–678.
25.Apparsundaram S, Ferguson SM, George A and Blakely RD. Molecular cloning of a human, hemicholinium–3–sensitive choline transporter. Biochem. Biophys. Res. Comm. 2000; 276:862–867.
26.Schroeter S,Apparsundaram Sand Blakely RD. Immunolocalization of cocaine–and antidepressant–sensitive norepinephrine transporters in rat brain. J. Comp. Neurol. 2000; 420:211–232.
27.Bauman AL, Apparsundaram S, Ramamoorthy S, Wadzinski BE, Vaughan RA and Blakely RD. Cocaine and antidepressant–sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A. J. Neurosci. 2000; 20:7571–7578.
28.Apparsundaram S, Galli A, DeFelice L, Hartzell HC and Blakely RD. Acute regulation of norepinephrine transport: I. Protein–kinase C–linked muscarinic receptors influence transport capacity and transporter density in SK–N–SH cells. J. Pharmacol. Exp. Ther. 1998; 287:733–743.
29.Apparsundaram S, Schroeter S, Giovanetti E and Blakely RD. Acute regulation of norepinephrine transport: II. PKC–modulated surface expression of human norepinephrine transporter proteins. J. Pharmacol. Exp. Ther. 1998; 287:744–751
30.Zhu M–Y, Apparsundaram S, Blakely RD and Ordway GA. Downregulation of the human norepinephrine transporter in intact 293–hNET cells exposed to desipramine. J. Neurochem. 1998; 70:1547–1555.
31.Blakely RD, Ramamoorthy S, Schroeter S, Qian Y, Apparsundaram S, Galli A and DeFelice LJ. Regulated phosphorylation and trafficking of antidepressant–sensitive serotonin transporter proteins. Biological Psychiatry1998; 44:169–178.
32.Jayanthi LD, Apparsundaram S, Malone D, Miller D, Eppler M and Blakely RD. The Caenorhabditis elegans gene T23G5.5 encodes a cocaine–sensitive dopamine transporter: Molecular cloning and expression of CeDAT. Mol. Pharmacol. 1998; 54:601–609.
33.Apparsundaram S, Moore KR, Malone MD, Hartzell HC and Blakely RD. Molecular cloning and characterization of an l–epinephrine transporter from sympathetic ganglia of the Bullfrog, Rana catesbiana. J. Neurosci. 1997; 17:2691–2702.
34.Blakely RD and Apparsundaram S.Structural diversity in the catecholamine transporter gene family: Molecular cloning and characterization of an l–epinephrine transporter from bullfrog sympathetic ganglia. Advances in Pharmacology 1997; 42:206–210.
35.Apparsundaram Sand Eikenburg DC. Prejunctional alpha adrenoceptor desensitization in rat heart after chronic epinephrine treatment. J. Pharmacol. Exp. Ther. 1996; 278:862–870.
36.Apparsundaram Sand Eikenburg DC. Role of prejunctional beta adrenoceptors in rat cardiac sympathetic neurotransmission. J. Pharmacol. Exp. Ther. 1995; 272:519–526.
37.Bond RA, Leff P, Johnson TD, Milano CA, Rockman HA, McMinn TR, Apparsundaram S, Hyek MF, Kenakin TP, Allen LF and Lefkowitz RJ. Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the beta–2 adrenoceptors. Nature (Lond.) 1995; 374:272–275.
38.Vyas SJ, Apparsundaram S, Ricci A, Amenta F and Lokhandwala MF. Biochemical, autoradiographic and pharmacological evidence for the involvement of tubular DA–1 receptors in the natriuretic response to dopexamine hydrochloride. Naunyn–Schmeidberg’s Arch. Pharmacol. 1991; 343:21–30.
39.Chen C, Apparsundaram Sand Lokhandwala MF. Intrarenally produced angiotensinII opposes the natriuretic actions of the dopamine–1 receptor agonist fenoldopam in rats. J. Pharmacol. Exp. Ther.1991;256:486–491.
40.Apparsundaram S, Bhat RV, Santani, DD and Goyal RK. Presynaptic dopamine receptors in rat anococcygeus muscle. Indian J. Pharmacol. 1989; 21:120–128.