My research program investigates new diagnostic tools, mechanism of drug action, pathogenesis of malaria disease and epidemiology of drug resistance for P. falciparum.

Malaria is a “stealer of dreams” for most of Africa, which bears the brunt of more than 80% morbidity and mortality from this protozoan disease. I treated my first malaria patient as an intern at Washington University in 1988 and have been focused on this pathogen since that time.

My main research interest in malaria, has been the molecular biology of metals and how the quinolines interfere with heme iron sequestration into heme crystals called hemozoin. The laboratory is also investigating the Plasmodium biology of copper and zinc. Present and developing work includes new uses for existing drugs with creation of a library of more than 1,800 FDA approved drugs for which we have screened for antimalarial cellular activity.

Two additional areas include the pathogenesis of cerebral malaria with a coincubation of P. falciparum with a human brain endothelial model in order to study effects on endothelium and the pathogenesis of mother to child transmission of HIV in the setting of placental malaria.

On the population level, the laboratory is investigating new malaria diagnostics based on detection of hemozoin in the blood by laser desorption mass spectrometry and also detection of malaria proteins and DNA in the urine. The population dynamics of acquisition of immunity followed by microsatellites in young children in malaria endemic areas is also being explored.

We are also creating maps of malaria to focus control efforts.

Molecular Microbiology and Immunology, Plasmodium, malaria, iron,copper, zinc transport, hemozoin, metal heme crystal, chemotherapy, drug discovery, diagnosis, placental malaria, cerebral malaria, FDA drug library

Class Citizenship Award (The Netter Series) for Community Service (1988)

MAP Readers Digest International Fellowship (1988, Mussoorie, India)

Burroughs Wellcome Leadership Award A.M.A. (1994)

National Foundation of Infectious Diseases (NFID) New Investigator Matching Award 1999

Burroughs Wellcome Career Award in the Biomedical Sciences 1997-2000

Pew Scholars Award in Biomedical Sciences 2000-2004

1) Sullivan Jr. DJ, Gluzman IY and Goldberg DE: Plasmodium hemozoin formation mediated by histidine-rich proteins. Science 271:219-222 (1996).

2) Sullivan Jr. DJ, Gluzman IY, Russell DG and Goldberg DE: On the molecular mechanism of chloroquine's antimalarial action. Proc. Natl. Acad. Sci. USA 93:11865-70 (1996).

3) Sullivan Jr. DJ, Ayala YM and Goldberg DE: An unexpected 5' untranslated intron in the P. falciparum genes for histidine-rich proteins II and III. Mol. Biochem. Parasit. 83:247-251 (1996).

4) Sullivan Jr. DJ, Matile H Ridley, RG and Goldberg DE: A common mechanism for blockade of

of heme polymerization by antimalarial quinolines. J. Biol. Chem. 273:31103-31107 (1998).

5) Coban C, Ishii KJ, Sullivan Jr. DJ, Kumar N: Purified malaria pigment (hemozoin) enhances dendritic cell maturation and modulates the isotype of antibodies induced by a DNA vaccine. Infect Immun. 70:3939-43 (2002).

6) Demirev PA, Feldman AB, Kongkasuriyachai D, Scholl P, Sullivan Jr. DJ, Kumar N: Detection of malaria parasites in blood by laser desorption mass spectrometry. Anal. Chem. 74:3262-6 (2002).

7) Sullivan Jr. DJ: Theories on malarial pigment formation and quinoline action Int. J. Parasit. 32:1645–1653 (2002).

8) Noland G, Briones N and Sullivan Jr. DJ: The Shape And Size Of Hemozoin Crystals Distinguishes Diverse Plasmodium Species Mol. Biochem. Parasitol. 130:91-99 (2003).

9) Chong C and Sullivan Jr. DJ: Inhibition of heme crystal growth by antimalarials and other compounds:

implications for drug discovery Biochem. Pharm. 66:2201-2212 (2003).

10) Iyer J, Shi L, Shankar A and Sullivan Jr. DJ: Zinc protoporphyrin IX binds heme crystals to inhibit the process of crystallization in Plasmodium falciparumMolecular Medicine 9:175-182 (2003).

11) Brahmbhatt H, Kigozi G, Wabwire-Mangen F, Serwadda D, Sewakambo N, Lutalo T, Wawer M, Abramowsky C, Sullivan Jr. DJ and Gray R: The effects of placental malaria on mother-to-child HIV transmission in Rakai, Uganda. AIDS17:2539-2541(2003).

12) Rasoloson D, Shi L, Chong CR, Kafsack BF, Sullivan Jr. DJ: Copper pathways in Plasmodium falciparum infected erythrocytes indicate an efflux role for the copper P-ATPase. Biochem. J. 381:803-811(2004).

13) Scholl PF, Kongkasuriyachai D, Demirev PA, Feldman AB, Lin JS, Sullivan Jr. DJ and Kumar N: Rapid detection of malaria infection in vivo by laser desorption mass spectrometry. Am. J. Trop. Med. Hyg. 71:546–551 (2004).

14) Jain SK, Persaud D, Perl TM, Pass MA, Murphy KM, Pisciotta JM, Scholl PF, Casella JF and Sullivan Jr. DJ: Nosocomial Malaria via Saline Flush: Back To Basics. Emerg Infect Dis. 11(7):1097-9(2005).

15) Scholl PF, Tripathi AK and Sullivan Jr.DJ: Bioavailable Iron And Heme Metabolism In Plasmodium falciparum Curent Topics in Microbiology and Immunology 295:293-324 (2005).

16) Nyunt M, Pisciotta J, Feldman AB, Thuma P, Scholl PF, Demirev PA, Lin JS, Shi L, Kumar N and Sullivan Jr. DJ: Detection Of Plasmodium Falciparum In Pregnancy By Laser Desorption Mass Spectrometry Am J. Trop Med. Hyg. Sep;73(3):485-490 (2005).

17) Tripathi AK, Sullivan Jr.DJ, Stins MF: Plasmodium falciparum-infected erythrocytes increase intercellular adhesion molecule 1 expression on brain endothelium through NF-kappaB. Infect Immun. 74(6):3262-70 (2006).

18) Chong CR, Qian DZ, Pan F, Wei Y, Pili R, Sullivan DJ Jr, Liu JO. Identification of type 1 inosine monophosphate dehydrogenase as an antiangiogenic drug target. J Med Chem. 49(9):2677-80 (2006).

19) Hiremath GS, Sullivan Jr. DJ, Tripathi AK, Black RE: Sazawal S.Effect of Plasmodium falciparum parasitemia on erythrocyte zinc protoporphyrin.Clin Chem. 52(4):778-9 (2006).

20) Chong CR, Chen X, Shi L, Liu JO, Sullivan Jr. DJ: A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol. 2(8):415-6 (2006)

21) Chen X, Chong CR, Shi L, Yoshimoto T, Sullivan Jr. DJ, Liu JO: Inhibitors of Plasmodium falciparum methionine aminopeptidase 1b possess antimalarial activity Proc Natl Acad Sci U S A. 103:14548-53(2006)

22) Tripathi AK, Sullivan Jr. DJ, Stins MF: Plasmodium falciparum Infected Erythrocytes Decrease Integrity of Human Blood Brain Barrier Endothelial Cell Monolayers. J Infectious Diseases 2007 Apr 1 195:942-50

23) Mharakurwa S, Simoloka C, Thuma PE, Shiff CJ, Sullivan Jr. DJ: PCR detection of Plasmodium falciparum in human urine and saliva samples. Malar J. 8;5:103(2006)

24) Pisciotta JM, Coppens I, Tripathi AK, Scholl PF, Shuman J, Bajad S, Shulaev V, Sullivan Jr.DJ: The role of neutral lipid nanospheres in Plasmodium falciparum heme crystallization. Biochem J.402(1):197-204 (2007)

25) Chong CR, Xu J, Lu J, Bhat S, Sullivan Jr. DJ, Liu JO: Inhibition of angiogenesis by the antifungal drug itraconazole. ACS Chem Biol. 2(4):263-70 (2007)

26) Chong CR and Sullivan Jr. DJ: New uses for old drugs Nature 448:645-646 (2007)

27) Szklarczyk A, Stins M, Milward EA, Ryu H, Fitzsimmons C, Sullivan DJ Jr, Conant K. Glial activation and matrix metalloproteinase release in cerebral malaria. J Neurovirol. 13:2-10 (2007) Review.

28) Mlambo G, Sullivan DJ Jr, Mutambu SL, Soko W, Mbedzi J, Chivenga J, Gemperli A, Kumar N. High prevalence of molecular markers for resistance to chloroquine and pyrimethamine in Plasmodium

falciparum from Zimbabwe. Parasitol Res. 101:1147-51 (2007)

29) Mlambo G, Sullivan DJ Jr, Mutambu SL, Soko W, Mbedzi J, Chivenga J, Jaenisch T, Gemperli A, Kumar N. Analysis of genetic polymorphism in select vaccine candidate antigens and microsatellite loci in Plasmodium falciparum from endemic areas at varying altitudes. Acta Trop.102:201-5 (2007).

30) Howard CT, McKakpo US, Quakyi IA, Bosompem KM, Addison EA, Sun K, Sullivan DJ Jr, Semba RD.

Relationship of hepcidin with parasitemia and anemia among patients with uncomplicated Plasmodium

falciparum malaria in Ghana. Am J Trop Med Hyg. 77:623-6 (2007)

31) Mlambo G, Vasquez Y, LeBlanc R, Sullivan DJ Jr,, Kumar N. A filter paper method for the detection of

Plasmodium falciparum gametocytes by reverse transcription polymerase chain reaction. Am J Trop Med Hyg. Jan;78(1):114-6(2008).

32) Brahmbhatt H, Sullivan DJ Jr, Kigozi G, Askin F, Wabwire-Mangenm F, Serwadda D, Sewankambo N, Wawer M, Gray R. Association of HIV and malaria with mother-to-child transmission, birth outcomes, and child mortality. J Acquir Immune Defic Syndr. 47:472-6(2008).

33) Kifude CM, Rajasekariah HG, Sullivan DJ Jr, Stewart VA, Angov E, Martin SK, Diggs CL, Waitumbi JN. Enzyme-linked immunosorbent assay for detection of Plasmodium falciparum histidine-rich protein 2 in blood, plasma, and serum. Clin Vaccine Immunol. 15:1012-8.(2008)

34) Pisciotta JM, Sullivan DJ Jr,. Hemozoin: oil versus water. Parasitol Int. 2008 57:89-96. Review.

35) Srivastava K, Cockburn IA, Swaim A, Thompson LE, Tripathi A, Fletcher CA, Shirk EM, Sun H, Kowalska MA, Fox-Talbot K, Sullivan DJ Jr,, Zavala F, Morrell CN. Platelet factor 4 mediates inflammation in experimental cerebral malaria. Cell Host Microbe. Aug 14;4(2):179-87(2008)

36) Downey AS, Chong CR, Graczyk TK, Sullivan Jr. DJ Efficacy of pyrvinium pamoate against Cryptosporidium parvum infection in vitro and in a neonatal mouse model. Antimicrob Agents Chemother. 52:3106-12(2008)