A major focus of research in my laboratory is the development of a human malaria transmission-blocking vaccine. This form of immunity (largely mediated by antibodies) interferes with the development of sexual stages (male and female gametocytes) in the mosquitoes and can significantly reduce malaria transmission. Several antigens have been identified as targets for the development of such a vaccine. Currently we are evaluating these antigens in the form of naked DNA based vaccines for Plasmodium falciparum and Plasmodium vivax (major human parasites). Immune responses elicited in mice are nearly 100% effective and a modified prime – boost strategy in nonhuman primates has also revealed nearly complete transmission blocking immunity. Further studies are attempting to improve immonogenicity of DNA vaccines by modification of the plasmid backbone by insertion of CpG motifs, optimizing genes for optimum expression in mammalian cells, and delivery by in vivo electroporation.

In another project we have employed targeted gene disruption to investigate molecular mechanisms involved in the differentiation and development of sexual stages, crucial for malaria transmission. These gene knockout approaches have identified proteins such as Pfg27 and Pfs16 important in the biology of sexual stages. Current studies are now using microarray technology to investigate transcriptional differences in the wild type and knock out parasites. In a collaborative project we have also solved the X-ray crystal structure of Pfg27 to begin to gain further insights into their function in the parasites. Other projects initiated in the laboratory are beginning to develop high throughput approaches to exploit the gametocyte proteome database for identification of novel targets for transmission reduction. Recombinant and proteomic approaches applied to investigate interactions between parasite and the salivary glands of the mosquito vector have identified a putative novel parasite receptor termed SAGLIN.

Molecular characterization of genetic recombination machinery in the parasite and investigation of DNA damage response pathway represents other new areas of investigation initiated recently in the laboratory.

In other collaborative projects we are looking at interactions between malaria-helminths, malaria-TB, malaria-HIV, and detection of malaria by mass spectrometry.

Molecular Microbiology and Immunology, malaria transmission-blocking vaccine, DNA vaccine, Recombination, Targeted gene disruption, Coinfections involving malaria parasites and other pathogens (helminths, HIV, TB).

2000, AMTRA of JHU-BSPH

2002, Invention of the Year Award, JHU-APL

2002, R.W. Hart Prize in Research, JHU-APL

2003, McGhee Memorial Lecture of the American Society of Parasitology

2005, Ranbaxy Science Foundation Medical Science Award

2007, Elected Fellow AAAS

Lobo, C.A., Dhar, R. and Kumar, N. Immunization of mice with DNA-based Pfs25 elicits potent malaria transmission blocking antibodies. Infect. Immunity 67: 1688-1693 (1999).

Lobo, C.A.. Fujioka, H., Aikawa, M. and Kumar, N. Disruption of the Pfg27 locus in Plasmodium falciparum by homologous recombination leads to the loss of the sexual phenotype. Molecular CELL 3: 793-798, (1999).

Brennan, J. G.D., Kent, M., Dhar, R., Fujioka, H. and Kumar, Nirbhay. Anopheles gambiae salivary gland proteins as putative targets for blocking transmission of malaria parasites. Proc. Natl. acad. Sci. 97, 13859-13864 (2000).

Bhattacharyya, M., Hong, Z., Kongkasuriyachai, D. and Kumar Nirbhay. Plasmodium falciparum protein phosphatase Type 1 functionally complements a glc7 mutant in Saccharomyces cerevisea. Int. J. Parasitol. 32: 739-747 (2002).

Demirev, P.A., Feldman, A.B., Kongkasuriyachai, P. Scholl, D. Sullivan, and Kumar, N. Detection of malaria parasites in blood by laser desorption mass spectrometry. Anal. Chem. 74: 3262-3268 (2002).

Kumar, Nirbhay. Guest Editor for a Thematic issue “Malaria: progress, problems and plans in the genomic era”, Int. J. Parasitology 32, 1537-1538 (2002).

Kongkasuriyachai, D. and Kumar, Nirbhay. Functional characterization of sexual stage specific proteins in Plasmodium falciparum. Int. J. Parasitology 32, 1559- 1566 (2002).

Singh S.K., Sati, S.P., Kongkasuriyachai, D, Kumar, Nirbhay and Sharma, A. Expression, purification, crystallization and preliminary X-ray analysis of the sexual stage-specific protein Pfg27 from Plasmodium falciparum. Acta Crstallographica, D58, 1869-1870, (2002).

Kashamuka, M., Nzila , N., Mussey, L., Lubaki. N., Quinn , T.C., Bollinger, R. and Kumar, Nirbhay. Analysis of anti-malaria immune response during human immunodeficiency virus infection in adults in Kinshasa, Democratic Republic of Congo. Am. J. Trop. Med. Hyg. 68, 376-378 (2002).

Bhattacharyya, M. and Kumar Nirbhay. Identification and molecular characterization of DNA damaging agent induced expression of Plasmodium falciparum recombination protein PfRad51. Int. J. Parasitol. 33, 1385-1392 (2003).

Sharma, A., Sharma, I. Kongkasuriyachai, D. and Kumar, Nirbhay. Structure of a gametocyte protein essential for sexual development in Plasmodium falciparum Nature (Str. Biol.), 10, 197-203 (2003)

Coban, Cevayir and Kumar Nirbhay. Malaria DNA Vaccines. Current Trends in Immunology. 19-31 (Invited review, 2003).

Haddad, D and Kumar Nirbhay. The expanding universe of “Omes”: approaches to malaria drugs and vaccine design. Recent Research Developments in Immunology. Recent Res. Develop. Infection & Immunity, 1: 419-432 (Invited review, 2003).

Kongkasuriyachai, D., B-Andrews, L., Stowers A., Collins, W.E., Sullivan, J., Tsuboi, T. and Kumar, Nirbhay. Potent immunogenicity of DNA vaccines encoding Plasmodium vivax transmission blocking vaccine candidates Pvs25 and Pvs28-evaluation of homologous and heterologous prime-boost strategy. Vaccine 22; 3205-3213 (2004).

Kongkasuriyachai, D, Fujioka, H. and Kumar, N. Functional analysis of Plasmodium falciparum parasitophorous vacuole membrane protein (Pfs16) during gametocytogenesis and gametogenesis by targeted gene disruption. Mol. Biochem. Parasitol.133; 275-285 (2004).

Sehgal, A., Kumar, N., Carruthers, V., and Sharma S. Surface expression of ribosomal protein P0 on Toxoplasma gondii tachyzoites. Int. J. Parasitol. 33: 1589-94 (2003).

Coban, Cavayir, Phillip, M., Keister, D., and Kumar, Nirbhay. Induction of Plasmodium falciparum transmission blocking antibodies in nonhuman primates by DNA vaccines-evaluation of various prime-boost strategies. Infection and immunity 72: 253-259 (2004).

Coban, Cevayir, Ishii, Ken, Stowers A, Keister, D, Klinman, D and Kumar, N. Effect of CpG oligonucleotides on the immunogenicity of Pfs25, a Plasmodium falciparum transmission blocking vaccine antigen. Inf. Immunity 72: 584-588 (2004).

Bhattachrayya, M.K., Norris, D and Kumar, N. Molecular players of homologous recombination in protozoan parasites: implications for generating antigenic variation. Infection, Genetics and Evolution 9(2):91-98 (2004).

Scott, C, Kumar, N., Bishai, W and Manabe, Y. Plasmodium infection impairs containment of bacterial growth in the murine model of Mycobacterium tuberculosis infection. Am. J. Trop. Med. Hyg. 70: 144-148 (2004).

Scholl, P., Kongkasuriyachai, Plamen, D., Sullivan, D., Lin, J., Feldman, A and Kumar, Nirbhay. Validation of mass spectrometry detection of malaria-infected erythrocytes in vivo using a Plasmodium yoelii infection model in mice. Am. J. Trop. Med. Hyg. 71: 546-51( 2004).

Bhattacharyya, M. K., Bhattacharyya, S., Jayabalasingham, B. and Kumar, N. Characterization of kinetics of DNA-strand exchange and ATP hydrolysis activities of Plasmodium falciparum recombinase PfRad51, Mol. Biochem. Parasitol. 139: 33-39, (2005).

Coban, C., Ishii, K.J., Kawaii, T., Hemmi, H., Sato, S., Uematsu, S., Yamamoto, M., Takeuchi, O., Itagaki, S., Kumar, N., Horii, T., Akira, S. Toll-like receptor 9-mediated innate immune activation by malaria pigment hemozoin. J. Exp. Med. 201: 19-25 (2005).

Noland, G., Graczyk, T., Fried, B., Fitzgerald, E., Kumar, N. Exacerbation of Plasmodium yoelii malaria in Echinostoma caproni infected mice and abatement through anthelmintic treatment. J. Parasitol. 91: 944-948 (2005).

Kalume, De, Okulate, M, Zhong, J, Suresh, S, Kumar, N, Pandey, A. A proteomic analysis of salivary glands of female Anopheles gambiae mosquito. Proteomics. 5: (2005).

Kalume, DE, Suraj P, Zhong, Okulate M, Surendranath, V, Kumar, N, Pandey, A. Genome annotation using mass spectrometry-derived data. BMC Genomics 6: (2005).

Coban, C, Ishii, KJ, Gursel, M, Klinman, D and Kumar, N. Effect of plasmid backbone modification by different human CpG motifs on the immunogenicity of DNA vaccine vectors. J. Leuck. Biol. 78: 647-655 (2005).

Nyunt M, Pisciotta, J, Feldman, AF, 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. Trop. Med. Hyg. 73: 485-490 (2005).

Gaikwad, G, Richa Ashma, Nirbhay Kumar, Rajni Trivedi, V K Kashyap. 2005. Host microsatellite alleles in malaria predisposition? Malaria Journal 4:50 (2005).

Page, KP, Jedlicka, AE, Fakheri, B, Noland, GS, Kesavan, AK, Scott, AL, Kumar, N, Manabe, Y. Mycobaterium-induced potentiation of type 1 immune responses and protection against malaria are host specific. Infection & Immunity. 73: 8369-80 (2005).

Haddad, D, Maciel, J and Kumar, N. Infection with Plasmodium berghei boosts antibody responses primed by a DNA vaccine encoding gametocyte antigen Pbs48/45. Infection & Immunity. 74:2043-51 (2006)

Amy Cernetich, A., Garver, L.S., Jedlicka, A.E., Klein, P.W., Kumar, Nirbhay, Scott, A.L. and Sabra L. Klein, S.L. Sex differences in response to blood-stage malaria infection: involvement of gonadal steroids and IFN?. Infection & Immunity 74: 3190-3203 (2006).

Mlambo, G. and Kumar Nirbhay. A modified Plasmodium falciparum growth inhibition assay (GIA) to assess activity of plasma from malaria endemic areas. Exp. Parasitology. 115:211-214(2007).

Mlambo, G., Mutambu, S.L., Mdoluza, T, Soko, W., Mbedzi, J., Chivenga, J., Lanar, D. E., Singh, S., Carucci, D., Germpeli, A., Kumar, Nirbhay. Antibody responses to Plasmodium falciparum vaccine candidate antigens in three areas distinct with respect to altitude. Acta Tropica 10: 70-78 (2006).

Promeneur, D.,., Liu, Y., Maciel, J., Agre, P. and Kumar, Nirbhay. Evidence for a role of the Plasmodium berghei aquaglyceroporin (pbAQP) in the intrerythrocytic development of the malaria parasite. Proc. Natl. Acad. Sci. USA 104: 2211-2216 (2007).

Okulate, M., Kalume, D.E., Kristiansen, T., Bhattacharyy, M.K., Pandey, A. and Kumar Nirbhay. Identification and molecular characterization of a novel protein SAGLIN recognized by monoclonal antibodies affecting infectivity of Plasmodium sporozoite infectivity of salivary glands in An. gambiae. Insect Mol. Biol. 16 (6), 711-722 (2007).

Mlambo, G., Sullivan, D., Mutambu, S.L., Soko, W., Mbedzi, J., Chivenga, J., Germpeli, A., Kumar, Nirbhay. Analysis of genetic polymorphism in select vaccine candidate antigens and microsatellite loci in Plasmodium falciparum from endemic areas at varying altitudes. Acta Tropica 102: 201-205 (2007).

Noland, GS, Graczyk, TK, Fried, B and Kumar, N. Enhanced malaria parasite transmission from helminth co-infected mice. Am. J. Trop. Med. Hyg. 76:1051-56 (2007).

Mlambo, G., Sullivan, D., Mutambu, S.L., Soko, W., Mbedzi, J., Chivenga, J., Germpeli, A., Kumar, Nirbhay. High prevalence of molecular markers for resistance to chloroquine and sulfadoxine / pyrimethamine in P. falciparum from Zimbabwe. Parasitol. Res. DOI 10.1007/S00436-007-05-97-5 (2007)

Urban, JF, Steenhard, N, S-Aguilar, GI, Dawson, HD, Iweala, OI, Nagler, CR, Noland, GS, Kumar, N, Anthony, RM, S-Donohue, T, Weinstock, J, Gause, WC. Infection with parasitic nematodes confounds vaccination efficacy. Veterinary Parasitology. 148: 14-20 (2007, Invited Review).

Yangjian Liu, Dominique Promeneur, Aleksandra Rojek, Nirbhay Kumar, Jørgen Frøkiær, Søren Nielsen, Landon S. King, Peter Agre, and Jennifer M. Carbrey. Aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence. Proc. Natl. Acad. Sci. 104: 12560-64 (2007).

Kumar, Nirbhay. A vaccine to prevent transmission of human malaria: a long way to travel on a dusty and often bumpy road. Current Science. 92: 1535-1543 (Invited review for special section on Malaria, 2007).

Mlambo, G, Vasquez, Y, LeBlanc, E, Sullivan, D, Kumar, Nirbhay. An RT-PCR based detection of Plasmodium falciparum gametocytes using blood collected on filter papers. Am. J. Trop. Med. Hyg. 78: 114-116 (2008).

LeBlanc, R, Vasquez, Y, Hannaman, D and Kumar, Nirbhay. Markedly enhanced immunogenicity of a Pfs25 DNA based malaria transmission blocking vaccine by in vivo electroporation. Vaccine, 26: 185-192 (2008).

Midzi N, Sangweme D, Zinyowera S, Mapingure MP, Brouwer KC, Munatsi A, Mutapi F, Mudzore J, Kumar N , Woelk G, Mduluza T. The burden of polyparasitism among primary school children living in rural and commercial farming areas of Zimbabwe. Trans. R. Soc. Trop. Med. Hyg. Trans.Roy.Soc.Trop.Med.Hyg. 102: 1039-1045(2008).

Midzi N, Sangweme D, Zinyowera S, Mapingure MP, Brouwer KC, Kumar N , Mutapi F,Woelk G, Mduluza T. Efficacy and side effects of praziquantel treatment against Schistosoma haematobium infection among primary school children in Zimbabwe. Trans. Roy. Soc. Trop. Med. Hyg. 102:759-766 (2008).

Noland, G. S., Joseph F. Urban, Jr., Bernard Fried, Nirbhay Kumar. Counter-regulatoryanti-parasite cytokine responses during concurrent Plasmodium yoelii and intestinal helminth infections in mice. Experimental Parasitology 119: 272-278 (2008).

Mlambo, G, Maciel, J and Kumar, Nirbhay. Development of a mouse model to evaluate malaria transmission blocking vaccines using a transgenic Plasmodium berghei expressing target antigen Pfs25. Infection & Immunity, 76: 2018-2024 (2008).

Ellekvist, E.,, Jorge Maciel, Godfree Mlambo, Christina H. Ricke, Hanne Colding, Dan A. Klaerke, and Nirbhay Kumar. Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption. Proc. Natl. Acad. Sci. 105: 6398-6402 (2008).

Mahajan, B, Selvapandiyan, A, Gerald, NJ, Majam, V, Zheng, H, Tiwari, J, Fujioka, H, Moch, JK, Kumar, N, Nakhashi, HL, Kumar, S. Centrins, cell cycle regulation proteins in human malaria parasite Plasmodium falciparum. J. Biol. Chem. 283: 31871-83 (2008).

Mlambo, G. and Kumar, Nirbhay. Transgenic rodent Plasmodium berghei: tools for assessment of functional immunogenicity and optimization of human malaria vaccines. Eukaryotic CELL. 7: 1875-1879 (2008).

Ghosh AK, Devenport M, Jethwaney D, Kalume DE, Pandey A, Anderson VE, Sultan AA, Kumar Nirbhay and Jacobs-Lorena M. Malaria parasite invasion of the mosquito salivary gland requires interaction between the Plasmodium TRAP and the Anopheles saglin proteins. PLoS Pathogens, 5(1)e1000265 (2009).

Nyunt MM, Hendrix, CW, Bakhshi, RP, Kumar, Nirbhay, Shapiro, TA. Phase I/II evaluation of the prophylactic antimalarial activity of pafuramidine in healthy volunteers challenged with Plasmodium falciparum sporozoites. Am. J. Trop. Med. Hyg. 80: 528-535 (2009).

Sangweme, D, Shiff, C and Kumar, Nirbhay. Plasmodium yoelii: adverse outcome of non-lethal P. yoelii malaria during co-infection with Schistosoma mansoni in BALB/c mouse model. Experimental Parasitology: (2009, in press).

Chowdhury, RD., Angov, E, Kariuki, T, and Kumar, Nirbhay. A Potent Malaria Transmission Blocking Vaccine Based on Codon Harmonized Full Length Pfs48/45 Expressed in E. coli. Plos ONE: (in press, 2009).