There is a great need for new drugs for parasitic diseases, such as malaria, African Sleeping Sickness, Chagas' disease, and leishmaniasis. Each year, these diseases sicken or kill over 200 million people. Though some pharmaceutical companies devote some research effort to discover drugs to cure some of these diseases there is little done given the need; the people with these parasitic diseases have little money to pay for medicine. Wes's research group uses emerging knowledge about the genomes of these parasites to aid in rational drug discovery.
His group, in collaboration with 4 other groups in Pennsylvania, Argentina, England and Australia, has developed a website called TDRtargets.org which allows pharmaceutical companies and scientists to select optimal drug targets from the genomes of parasite.
His group is also involved in discovering the molecular targets of cell-active compounds that are potential drugs. They have discovered promising anti-parasitic compounds, based on enzymatic targets from the genomes of these parasites, that show great promise as drug leads. Some of the most promising compounds are inhibitors that block kinases necessary for parasite growth. The group uses structure based drug discovery, in collaboration with X-ray crystallographers and chemists, and pharmacokinetic and toxicology information from the laboratory, to optimize compounds to become drug candidates for clinical development.
Guiguemde WA, Shelat AA, Bouck D, Duffy S, Crowther GJ, Davis PH, Smithson DC, Connelly M, Clark J, Zhu F, Jiménez-Díaz MB, Martinez MS, Wilson EB, Tripathi AK, Gut J, Sharlow ER, Bathurst I, El Mazouni F, Fowble JW, Forquer I, McGinley PL, Castro S, Angulo-Barturen I, Ferrer S, Rosenthal PJ, Derisi JL, Sullivan DJ, Lazo JS, Roos DS, Riscoe MK, Phillips MA, Rathod PK, Van Voorhis WC, Avery VM, Guy RK(2010). Chemical genetics of Plasmodium falciparum. Nature. 465(7296):311-5. PMID: 20485428
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Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, Derocher AE, Inampudi KK, Kim JE, Arakaki TL, Murphy RC, Zhang L, Napuli AJ, Maly DJ, Verlinde CL, Buckner FS, Parsons M, Hol WG, Merritt EA, Van Voorhis WC (2010). Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nat Struct Mol Biol. 17:602-7. PMID: 20436472.
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Ojo KK, Arakaki TL, Napuli AJ, Inampudi KK, Keyloun KR, Zhang L, Hol WGJ, Verlinde CLMJ, Merritt EA, Van Voorhis WC (2011). Structure determination of glycogen synthase kinase-3 from Leishmania major and comparative inhibitor structure–activity relationships with Trypanosoma brucei GSK-3. Mol Biochem Parasitol (2011) 176(2):98-108. PMID: 21195115.
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Engelson, E.J., Buckner F.S., Van Voorhis W.C. (2011). An Essential Farnesylated Kinesin in Trypanosoma brucei. PLoS One 2011;6(11):e26508.
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Magarinos MP, Carmona SP, Crowther GJ, Ralph SA, Roos DA, Shanmugam D, Van Voorhis WC and Aguero F (2012). TDR Targets: a chemogenomics resource for neglected diseases. Nucl Acids Res. 40(Database issue):D1118-27.
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Nwaka S, Besson D, Ramirez B, Maes L, Matheeussen A, Bickle Q, Mansour NR, Yousif F, Townson S, Gokool S, Cho-Ngwa F, Samje M, Misra-Bhattacharya S, Murthy PK, Fakorede F, Paris JM, Yeates C, Ridley R, Van Voorhis WC, Geary T. Integrated Dataset of Screening Hits against Multiple Neglected Disease Pathogens. PLoS Negl Trop Dis. 2011 Dec;5(12):e1412. Epub 2011 Dec 20.
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Ojo KK, Pfander C, Mueller NR, Burstroem C, Larson ET, Bryan CM, Fox AM, Reid MC, Johnson SM, Murphy RC, Kennedy M, Mann H, Leibly DJ, Hewitt SN, Verlinde CL, Kappe S, Merritt EA, Maly DJ, Billker O, Van Voorhis WC. Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors. J Clin Invest. 2012 Jun 1; 122(6):2301-5.
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Leibly DJ, Nguyen TN, Kao LT, Hewitt SN, Barrett LK, Van Voorhis WC. Stabilizing additives added during cell lysis aid in the solubilization of recombinant proteins. PLoS One. 2012; 7(12):e52482.
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Baugh L, Gallagher LA, Patrapuvich R, Clifton MC, Gardberg AS, Edwards TE, Armour B, Begley DW, Dieterich SH, Dranow DM, Abendroth J, Fairman JW, Fox D 3rd, Staker BL, Phan I, Gillespie A, Choi R, Nakazawa-Hewitt S, Nguyen MT, Napuli A, Barrett L, Buchko GW, Stacy R, Myler PJ, Stewart LJ, Manoil C, Van Voorhis WC. Combining functional and structural genomics to sample the essential burkholderia structome. PLoS One. 2013;8(1):e53851.
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