Kayode K.
Ojo
PhD
related links
bio
Dr. Ojo's research focuses on studies to better understand the molecular biology of antimicrobial resistance and on the development of novel, robust, safe and affordable antimicrobial agents that can treat debilitating parasitic diseases.
Ongoing studies of calcium-dependent protein kinases of Toxoplasma gondii and Cryptosporidium parvum may facilitate the development of a very safe and effective drug therapy. We have identified a uniquely large pocket in the ATP-binding region of Toxoplasma gondii, Neospora caninum and Cryptosporidium parvum calcium-dependent protein kinase-1 (CDPK-1) that allows the development of inhibitors that have negligible to no effects on human kinases. Our work demonstrates that inhibition of some members of Phylum Apicomplexa's CDPKs prevents invasion of host cells and stops parasite replication.
We are further utilizing the experience and tools developed from our studies on Toxoplasma gondii, Neospora caninum and Cryptosporidium parvum to design a new class of malaria transmission-blocking compounds. These compound series act via inhibition of PfCDPK4 in efficiently blocking Plasmodium parasite infection of mosquitoes, preventing the transmission of malaria to humans. Our studies indicate that this strategy could lead to non-toxic, selective inhibitors that block malaria transmission to mosquitoes, have favorable oral pharmacokinetic properties, and are excellent leads for further drug development. Since CDPK4 genes of all Plasmodium species with database entries are highly conserved, an effective lead compound will likely be useful in blocking the transmission of all 5 spp. known to cause human malaria; a significant public health implication and benefit.
education & training
PhD Pharmaceutical Microbiology, University of Ibadan, Nigeria (2002)
Post-Doctoral Fellowship, Allergy and Infectious Diseases, University of Washington, Seattle, WA (2006-2009)
honors
Research Fellowship from the Gesellschaft der Freunde der Kleintierforschung (GdFuF) German Government
ICAAC/Wyeth ID Fellows Grant to the 48th Annual ICAAC/46th IDSA Annual Meeting in Washington, D.C. (2008)
publications
Ojo K.K., Eastman RT, Vidadala R, Zhang Z, Rivas KL, Choi R, Lutz JD, Reid MC, Fox AMW, Hulverson MA, Kennedy M, Isoherranen N, Kim LM, Comess KM, Kempf DJ, Verlinde CLMJ, Su X-Z, Kappe S, Maly D.J., Fan E., and Van Voorhis WC. (2014) Specific inhibitor of PfCDPK4 blocks malaria transmission: Chemical-genetic validation. Journal of Infectious Diseases. 2014; 209(2):275-284.
• PubMed Abstract
Ojo KK, Pfander C, Mueller N.R., Burstroem C, Larson ET, Bryan CM, Fox AMW, Reid MC, Johnson SM, Murphy RC, Kennedy M, Mann H, Leibly DJ, Hewitt SN, Verlinde CLMJ., Kappe S, Merritt EA, Maly DJ, Billker O, and Van Voorhis WC. Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors. Journal of Clinical Investigation. 2012; 122(6):2301-2305.
• PubMed Abstract
Castellanos-Gonzalez A, White CA Jr, Ojo KK, Vidadala R, Zhang Z, Reid MC, Fox AMW, Keyloun KR, Rivas K, Irani A, Dann SM, Fan E, Maly DJ, and Van Voorhis WC. A novel calcium dependent protein kinase inhibitor as a lead compound for treating Cryptosporidiosis. Journal of Infectious Diseases. 2013; 2088(8):1342-1348.
• PubMed Abstract
Ojo KK, Arakaki TL, Napuli AJ, Inampudi KK, Keyloun KR, Zhang L, Hol WGJ, Verlinde CLMJ, Merritt EA and Van Voorhis WC. Structure Determination of Glycogen Synthase Kinase-3 from Leishmania major and Comparative Inhibitor Structure-Activity Relationships with Trypanosoma brucei GSK-3. Molecular and Biochemical Parasitology. 2011; 176(2):98-108. • PubMed Abstract
Murphy RC, Ojo KK, Larson ET, Castellanos-Gonzalez A, Perera BGK, Keyloun KR, Kim JE, Bhandari JG, Muller NR, Verlinde CLMJ, White CA, Merritt EA, Van Voorhis WC, and Maly DJ. Discovery of Potent and Selective Inhibitors of Calcium-Dependent Protein Kinase 1 (CDPK1) from C. parvum and T. gondii. ACS Medicinal Chemistry Letters. 2010; 1(7):331-335.
• PubMed Abstract
Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, DeRocher AE, Inampudi KK, Kim JE, Arakaki TL, Murphy R, Zhang L, Napuli AJ, Maly DJ, Verlinde CLMJ, Buckner FS, Parsons M, Hol WGJ, Merritt EA and Van Voorhis WC.Toxoplasma gondii Calcium-Dependent Protein Kinase 1 is a target for selective kinase inhibitors. Nature structural and molecular biology. 2010; 17:602-607.
• BioMed article
Ojo KK, Gillespie JR, Riechers AJ, Napuli AJ, Verlinde CLMJ, Buckner FS, Gelb MH, Domostoj MM, Wells SJ, Scheer A, Wells TNC and Van Voorhis WC. Glycogen Synthase Kinase 3 is a Potential Drug Target for African Trypanosomiasis Therapy. Antimicrobial Agents and Chemotherapy. 2008; 52(10):3710-17.
• PubMed Abstract