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My research program investigates new diagnostic tools, mechanism of drug action and epidemiology of drug resistance for P. falciparum. Diagnosis-The laboratory is developing ELISA based HRP II and aldolase antigen testing to make quantitative determination of parasitemia in serum and urine. A hemozoin detection test by the method of mass spectroscopy is in development with Peter Scholl, Nirbhay Kumar and reseachers at JHU Applied Physics Lab. Drug action- This area focuses on metal metabolism perturbed by antimalarial chemotherapy. We investigate the formation of iron rich hemozoin heme crystals and its inhibition by the quinolines. We are also investigating the the basic cell biology of iron, copper and zinc by characterization of genes for metal storage, transport and respective chaperones. We are developing mass spectroscopy for defining the metablolome (metabolites not encoded by the genome) to compare with the transcriptome in the investigation of drug effects on the parasite. Artemisinin also requires bioavailable iron for it mechanism of action to inhibit the calcium P-ATPASE pump. The laboratory is also screening a library of over 2,000 available FDA approved drugs for malaria inhibition. Epidemiology of drug resistance- We are performing PCR based genotyping of drug resistance genes for chloroquine, antifolates, and mefloquine from fingerprick samples of blood on filter paper. In addition we are utilizing microsatellite allele determination in collaboration with Doug Norris for assessment of multiplicity of infection and duration of infection in longitudinal studies. Placental Malaria- We are studying the interaction if HIV and malaria during pregnancy. CONTACT DR. SULLIVAN Johns Hopkins University email: dsulliva@jhsph.edu LINKS SELECTED PUBLICATIONS Jain SK, Persaud D, Perl TM, Pass MA, Murphy KM, Pisciotta JM, Scholl PF, Casella JF, Sullivan DJ. Nosocomial malaria and saline flush. Emerg Infect Dis 11:1097-1099, 2005. Article Nyunt M, Pisciotta J, Feldman AB, Thuma P, Scholl PF, Demirev PA, Lin JS, Shi L, Kumar N, Sullivan DJ. Detection of Plasmodium falciparum in pregnancy by laser desorption mass spectrometry. Am J Trop Med Hyg 73:485-490, 2005. Article Pisciotta JM, Ponder EL, Fried B, Sullivan D. Hemozoin formation in Echinostoma trivolvis rediae. Int J Parasitol 35:1037-1042, 2005. Abstract Rasoloson D, Shi L, Chong CR, Kafsack BF, Sullivan DJ. Copper pathways in Plasmodium falciparum infected erythrocytes indicate an efflux role for the copper P-ATPase. Biochem J 803-811, 2004. Article Scholl PF, Kongkasuriyachai D, Demirev PA, Feldman AB, Lin JS, Sullivan DJ Jr, Kumar N. Rapid detection of malaria infection in vivo by laser desorption mass spectrometry. Am J Trop Med Hyg 71:546-551, 2004. Abstract Brahmbhatt H, Kigozi G, Wabwire-Mangen F, Serwadda D, Sewakambo N, Lutalo T, Wawer M, Abramowsky C, Sullivan D, Gray R. The effects of placental malaria on mother-to-child HIV transmission in Rakai, Uganda. AIDS 17:2539-2541, 2003. Abstract Chong C, Sullivan D. Inhibition of heme crystal growth by antimalarials and other compounds: implications for drug discovery. Biochem Pharm 66:2201-2212, 2003. Abstract Iyer J, Shi L, Shankar A, Sullivan D. Zinc protoporphyrin IX binds heme crystals to inhibit the process of crystallization in Plasmodium falciparum. Mol Med 9:175-182, 2003. Abstract Noland G, Briones N, Sullivan D. The shape and size of hemozoin crystals distinguishes diverse Plasmodium species. Mol Biochem Parasitol 130:91-99, 2003. Abstract Akompong T, Kadekoppala M, Harrison T, Oksman A, Goldberg DE, Fujioka H, Samuel BU, Sullivan D, Haldar K. Trans-expression of a Plasmodium falciparum histidine-rich protein II (HRPII) reveals sorting of soluble proteins in the periphery of the host erythrocyte and disrupts transport to the malarial food vacuole. J Biol Chem 277:28923-28933, 2002. Article Coban C, Ishii KJ, Sullivan DJ, Kumar N. Purified malaria pigment (hemozoin) enhances dendritic cell maturation and modulates the isotype of antibodies induced by a DNA vaccine. Inf Immun 70:3939-3943, 2002. Article Demirev PA, Feldman AB, Kongkasuriyachai D, Scholl P, Sullivan D Jr, Kumar N. Detection of malaria parasites in blood by laser desorption mass spectrometry. Anal Chem 15;74:3262-3266, 2002. Abstract Sullivan D. Theories on malarial pigment formation and quinoline action. Int J Parasitol 32:1645-1653, 2002. Abstract Chen MM, Shi L, Sullivan DJ. Haemoproteus and Schistosoma synthesize heme polymers similar to Plasmodium hemozoin and beta-hematin. Mol Biochem Parasitol 113:1-8, 2001. Abstract Hayward RE, Sullivan DJ, Day KP. Plasmodium falciparum: Histidine-rich protein II is expressed during gametocyte development. Exp Parasit 96:139-146, 2001. Abstract | ||||||||||||||||