Assistant Professor
Department of Molecular Microbiology and Immunology
Bloomberg School of Public Health

sprigge@jhsph.edu

E4628 Public Health
615 N. Wolfe Street
Baltimore, MD 21205

Office: 443-287-4822
Lab: 443-287-6695

Malaria, a disease caused by protozoan parasites, is one of the most dangerous infectious diseases, claiming millions of lives and infecting hundreds of millions of people annually. Malaria parasites contain an essential organelle called the apicoplast that is thought to have arisen through endosymbiosis of an algal cell which had previously incorporated a cyanobacterium.  Due to its prokaryotic origin, the apicoplast contains a range of metabolic pathways that differ significantly from those of the human host.  We are investigating biochemical pathways found in the apicoplast, particularly those required for the biosynthesis and modification of fatty acids.  This metabolism should require several enzyme cofactors such as pantothenate, lipoic acid, biotin and iron-sulfur clusters.  We are interested in these cofactors, how they are acquired, how they are used, and whether they are essential for the growth of blood stage malaria parasites.  We approach these questions with a combination of cell biology, genetic, biophysical and biochemical techniques.

Selected Publications
Gallagher, J.R., and S.T. Prigge (2009) Plasmodium falciparum acyl carrier protein crystal structures in disulfide-linked and reduced states and their prevalence during blood stage growth. Proteins: Struc. Func. Bioinf. (in press)

Spalding, M.D., and S.T. Prigge (2009) The amidase domain of lipoamidase specifically inactivates lipoylated proteins in vivo. PLoS One (in press)

Lee, P.J., J.B. Bhonsle, H.W. Gaona, D.P. Huddler, T.N. Heady, M. Kreishman-Deitrick, A. Bhattacharjee, W.F. McCalmont, L. Gerena, M. Lopez-Sanchez, N.E. Roncal, T.H. Hudson, J.D. Johnson, S.T. Prigge, and N.C. Waters (2009) Targeting the fatty acid biosynthesis enzyme, PfKASIII, in the identification of novel antimalarial agents. J. Med. Chem. 52:952-963.

Spalding, M.D., and S.T. Prigge (2008) Malaria pulls a FASt one. Cell Host & Microbe 4:509-511.

Lu, J.Z., and S.T. Prigge (2008) The tail of mycolic acids. Chem. Biol. 4:309-310.

Allary, M., and S.T. Prigge. (2008) Fatty Acid Synthesis in Protozoan Parasites. In: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester.

Lu, J.L., S.P. Muench, M. Allary, S.A. Campbell, C.W. Roberts, E. Mui, R.L. McLeod, D.W. Rice, and S.T. Prigge. (2007) Type I and type II fatty acid biosynthesis in Eimeria tenella: Enoyl reductase activity and structure. Parasitology 134:1949-1962.

Allary, M., J.Z. Lu, L. Zhu, and S.T. Prigge. (2007) Scavenging of the cofactor lipoate is essential for the survival of the malaria parasite Plasmodium falciparum. Mol. Micro. 63:1331-1344.

Muench, S.P., S.T. Prigge, R. McLeod, J.B. Rafferty, M.J. Kirisits, C.W. Roberts, E.J. Mui, and D.W. Rice. (2007) Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents. Acta. Crystallogr. D Biol. Crystallogr. D 63:328-338.

Ferguson, D.J., S.A. Campbell, F.L. Henriquez, L. Phan, E. Mui, T.A. Richards, S.P. Muench, M. Allary, J.Z. Lu, S.T. Prigge, F. Tomley, M.W. Shirley, D.W. Rice, R. McLeod and C.W. Roberts. (2007) Enzymes of type II fatty acid synthesis and apicoplast differentiation and division in Eimeria tenella. Int. J. Parasitol. 37:33-51.

Muench, S.P., S.T. Prigge, L. Zhu, M.J. Kirisits, C.W. Roberts, S. Wernimont, R. McLeod and D.W. Rice. (2006) Expression, purification and preliminary crystallographic analysis of the Toxoplasma gondii enoyl reductase. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. 62:604-606.

Chen, Y., D. Jirage, D. Caridha, A.K. Kathcart, E.A. Cortes, R.A. Dennull, J.A. Geyer, S.T. Prigge and N.C. Waters. (2006) Identification of an effector protein and gain-of-function mutants that activate Pfmrk, a malarial cyclin-dependent protein kinase. Mol. Biochem. Parasit. 149:48-57.

Siebert, X., B.A. Eipper, R.E. Mains, S.T. Prigge, N.J. Blackburn, and L.M. Amzel. (2005) The catalytic CuB site of PHM also plays a critical structural role. Biophys. J. 89:3312-3319.

Geyer, J.A., S.T. Prigge, and N.C. Waters. (2005) Targeting malaria with specific CDK inhibitors. Biochim. Biophys. Acta. 1754:160-170.

Lu, J.Z., P.J. Lee, N.C. Waters, and S.T. Prigge. (2005) Fatty acid synthesis as a target for antimalarial drug discovery. Comb. Chem. High Throughput Screen. 8:15-26.

Ferguson, D.J.P., B.U. Samuel, F.L. Henriquez, M.J. Kirisits, S.P. Muench, S.T. Prigge, D.W. Rice, C.W. Roberts, and R.L. McLeod. (2005) Maternal inheritance and stage-specific variation in the apicoplast in Toxoplasma gondii during development in the intermediate and definitive host. Eukaryot. Cell 4:814-26.

Keenan, S.M., J.A. Geyer, W.J. Welsh, S.T. Prigge, and N.C. Waters. (2005) Rational inhibitor design and iterative screening in the identification of selective plasmodial cyclin dependent kinase inhibitors. Comb. Chem. High Throughput Screen. 8:15-26.

Prigge, S.T., R.E. Mains, B.A. Eipper, and L.M. Amzel. (2004) Dioxygen binds end-on to mononuclear-copper in a precatalytic enzyme complex. Science 304:864-867.

Bhattacharjee, A.K., J.A. Geyer, C.L. Woodward, A.K. Kathcart, D.A. Nichols, S.T. Prigge, Z. Li, and N.C. Waters. (2004) A three dimensional in silico pharmacophore model for inhibition of Plasmodium falciparum cyclin dependent kinases and discovery of different classes of novel Pfmrk specific inhibitors. J. Med. Chem. 47:5418-5426.