There is a great need to develop novel malaria and dengue control strategies because of the failures of current eradication approaches and the logistical difficulties to implement them. One interesting aspect of these diseases is that the mosquito that transmits the pathogens can mount immune responses against the infection that will kill a large proportion of malaria parasites and inhibit the dengue virus. My group is pursuing research to understand how the mosquito’s immune system is capable of blocking pathogens and how we can use this knowledge to develop resistant mosquitoes. We have already made great advances towards this goal, through several independent but synergistically interacting projects, and identified several factors that are responsible for conferring resistance to the parasite and the virus in their respective vectors. We are currently generating genetically modified mosquitoes with an enhanced immune system to test whether this approach is viable for the development of control strategies. Our competitive advantage derives from a unique blend of core competencies in molecular entomology, innate immunity and functional genomics, as well as the access to state-of-the-art research infrastructure at the Johns Hopkins Malaria Research Institute. We are also engaged in other related projects that focus on: a. mosquito’s interaction with microbes in the environment that could influence the capacity to transmit human pathogens; b. the function of the mosquito’s biological clock, and how it could be used to inhibit their blood feeding behavior. The long-term goal of my research program is to broaden the basic knowledge of this field and provide new tools for the development of disease control strategies.

See also:

http://www.dimopoulosgroup.org/

http://malaria.jhsph.edu/people/faculty/george_dimopoulos/

Malaria, Anopheles gambiae, Plasmodium, Aedes aegypti, Dengue, innate immunity, transcriptomics

Souza-Neto JA, Sim S, and Dimopoulos G (2009) Evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc. Natl. Acad. Sci. USA. Accepted for publication.

Erickson SA, Xi Z, Mayhew GF, Ramirez JL, Aliota MT, Christensen BM, Dimopoulos G (2009) Mosquito Infection Responses to Developing Filarial Worms. PLoS Trop. Negl. Dis. Accepted for publication.

Sim S, Ramirez JL, and Dimopoulos G (2009) Molecular discrimination of mosquito vectors and their pathogens. Expert Review of Molecular Diagnostics. Accepted for publication.

Baton LA, Robertson A, Warr E, Strand MR, Dimopoulos G. (2009) Genome-wide transcriptomic profiling of Anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and Plasmodium berghei infection. BMC Genomics 10(1):257.

Dong Y., Manfredini F. and Dimopoulos G. (2009) Implication of the Mosquito Midgut Microbiota in the Defense Against Malaria Parasites. PLoS Pathogens, 5(5), e1000423.

Sessions OM, Barrows, NJ, Souza-Neto JA, Robinson TJ, Hershey CL, Rodgers MA, Ramirez JL, Dimopoulos G, Yang PL, Pearson JL, Garcia-Blanco MA (2009) Discovery of Dengue Virus Host Factors in Insects and Humans. Nature, 458(7241):1047-1050.

Dong Y. and Dimopoulos G. (2009) Anopheles fibrinogen-related proteins provide expanded pattern recognition capacity against bacteria and malaria parasites. J Biol Chem., Feb 4, EPUB ahead of print.

Garver L., Dong Y. and Dimopoulos G. (2009) Caspar control resistance to Plasmodium falciparum in diverse Anopheline species. PloS Pathogens, 5(3):e1000335.

Das S., and Dimopoulos G. (2008) Molecular analysis of photic inhibition of blood-feeding in Anopheles gambiae. BMC Physiology 16;8(1):23.

Ramirez JL., Garver L., and Dimopoulos G. (2008) Challenges and Approaches for Mosquito Targeted Malaria Control. Curr. Mol. Medicine. In press.

Abrantes A., Dimopoulos G., Grosso AR., do Rosário VE. and Silveira H. (2008) Chloroquine mediated modulation of Anopheles gambiae gene expression. PLoS ONE 2;3(7).

Xi Z., Ramirez JL., Dimopoulos G. (2008) The Aedes aegypti Toll pathway controls dengue virus infection. PLoS Pathogens 4(7).

Gomulski LM., Dimopoulos G., Xi Z., Soares MB., Bonaldo MF., Malacrida AR., Gasperi G. (2008) Gene discovery in an invasive tephritid model pest species, the Mediterranean fruit fly, Ceratitis capitata. BMC Genomics 2008, 9:248.

Baton L, Garver L, Xi Z and Dimopoulos G. (2008) Functional genomics studies on the innate immunity of disease vectors. Insect Science, 15:15-27.

Warr, E., Das, S., Dong, Y., and Dimopoulos, G. (2008) The Gram-Negative Bacteria-Binding Protein gene family: Its role in the innate immune system of Anopheles gambiae and in anti-Plasmodium defense. Insect Mol. Biol., 17:39-51.

Garver, LS, Xi, Z and Dimopoulos, G. (2008) Immunoglobulin superfamily members play an important role in the mosquito immune system, Dev. & Comp. Immunol. 32:519-31.

Dimopoulos G. (2007) Building a better mosquito: identifying the genes enabling malaria and dengue fever resistance in A. gambiae and A. aegypti mosquitoes. J Vis Exp. (5):233.

Aguilar, R., Das, S., Dong, Y. and Dimopoulos, G. (2007) Continuous exposure to Plasmodium results in decreased susceptibility and transcriptomic divergence of the Anopheles gambiae immune system. BMC Genomics, 8:451.

Baton, L., Warr, E., Hoffman S. and Dimopoulos, G. (2007) Programmed cell death during malaria parasite infection of the vertebrate host and mosquito vector. In Programmed Cell Death in Protozoa, Edited by Martin P. Landes Bioscience, Springer.

Garver, L.S., Baton, L., and Dimopoulos, G. (2007) Mosquito Immunity to the Malaria Parasite. In Insect Immunology, Edited by Nancy Beckage. Elsevier.

Waterhouse, RM, Kriventseva, EV, Meister, S, Xi, Z, Alvarez, KV, Bartholomay, LC, Barillas-Mury, C, Bian, G, Blandin, S, Christensen, BM, Dong, Y, Jiang, H, Kanost, MR, Koutsos, AC, Levashina, EA, Li, J, Ligoxygakis, P, MacCallum, RM, Mayhew, GF, Mendes, A, Michel, K, Osta, MA, Paskewitz, S, Shin SW, Vlachou, D, Wang, L, Wei, W, Zheng, L, Zou, Z, Severson, DW, Raikhel, AS, Kafatos, FC, Dimopoulos, G, Zdobnov, EM, Christophides, GK (2007) Evolutionary dynamics of immune-related genes and pathways in disease vector mosquitoes. Science, 316:1738-1743.

Nene V, Wortman JR, Lawson D, Haas B, Kodira C, Tu ZJ, Loftus B, Xi Z, Megy K, Grabherr M, Ren Q, Zdobnov EM, Lobo NF, Campbell KS, Brown SE, Bonaldo MF, Zhu J, Sinkins SP, Hogenkamp DG, Amedo P, Arsenburger P, Atkinson PW, Bidwell S, Biedler J, Birney E, Bruggner RV, Costas J, Coy MR, Crabtree J, Crawford M, Debruyn B, Decaprio D, Eiglmeier K, Eisenstadt E, El-Dorry H, Gelbart WM, Gomes SL, Hammond M, Hannick LI, Hogan JR, Holmes MH, Jaffe D, Johnston SJ, Kennedy RC, Koo H, Kravitz S, Kriventseva EV, Kulp D, Labutti K, Lee E, Li S, Lovin DD, Mao C, Mauceli E, Menck CF, Miller JR, Montgomery P, Mori A, Nascimento AL, Naveira HF, Nusbaum C, O'leary SB, Orvis J, Pertea M, Quesneville H, Reidenbach KR, Rogers YH, Roth CW, Schneider JR, Schatz M, Shumway M, Stanke M, Stinson EO, Tubio JM, Vanzee JP, Verjovski-Almeida S, Werner D, White O, Wyder S, Zeng Q, Zhao Q, Zhao Y, Hill CA, Raikhel AS, Soares MB, Knudson DL, Lee NH, Galagan J, Salzberg SL, Paulsen IT, Dimopoulos G, Collins FH, Bruce B, Fraser-Liggett CM, Severson DW. (2007)Genome Sequence of Aedes aegypti, a Major Arbovirus Vector. Science, 316:1718-1723.

Warr, E., Aguilar, R., Dong, Y., Mahairaki V. and Dimopoulos, G. (2007) Spatial and sex-specific dissection of the Anopheles gambiae midgut transcriptome. BMC Genomics, 8:37.

Warr, E., Lambrechts, L., Bourgouin C., Koella, J., and Dimopoulos, G. (2006) Melanization of Sephadex Beads in Anopheles gambiae is controlled by anti-Plasmodium immune factors. Insect Biochemistry and Molecular Biology, 36:769-778

Baton, L., Dong, Y., Li, J. and Dimopoulos, G. (2006) Variation in mosquito immunity to Plasmodium. Proceedings of the 11th International Congress of Parasitology.

Mair G., Braks J.A.M., Garver L., Wiegant J.K.A.G., Hall Dirks, R.W., Khan S.M., Dimopoulos, G., Janse C.J., Waters A.P. (2006) Regulation of sexual development of Plasmodium by translational repression. Science, 313(5787):667-669.

Dong Y., Taylor H.E., and Dimopoulos, G. (2006) AgDscam, a hyper variable immunoglobulin domain containing receptor of the Anopheles gambiae innate immune system. PLoS Biology 4: e229.

Dong Y., Aguilar R., Xi Z., Warr E., Mongin E., and Dimopoulos, G. (2006) Anopheles gambiae immune responses to human and rodent Plasmodium parasite species. PLoS Pathogens 6: 1-13.

Heard NA, Holmes CC, Stephens DA, Hand DJ and Dimopoulos G (2005) Bayesian Co-clustering of Anopheles Gene Expression Time Series: A Study of Immune Defense Response To Multiple Experimental Challenges. Proc Natl Acad Sci U S A 102:16939-16944.

Aguilar R, Dong Y, Warr E and Dimopoulos, G. (2005) Anopheles infection responses: laboratory models versus field malaria transmission systems. Acta Tropica 95(3):285-291.

Xu, XJ., Dong, Y., Abraham, EG., Kocan, A., Srinivasan, P., Sinden, RE., Ribeiro, JMC., Jacobs-Lorena, M., Kafatos FC., and Dimopoulos, G. (2005) Transcriptome analysis of Anopheles stephensi-Plasmodium berghei interactions. Mol Biochem Parasitol. 142:76-87.

Both, M., Eckert, SE., Csukai, M., Dimopoulos, G., Spanu PD. (2005) Transcript profiles of Blumeria graminis development during infection reveal a cluster of genes that are potential virulence determinants. Molecular Plant-Microbe Interactions. 18(2):125-133.

Aguilar, R., Jedlicka, AE. Mintz,M., Mahairaki, V., Scott AL. and Dimopoulos, G. (2005) Global gene expression analysis of Anopheles gambiae responses to microbial challenge. Insect Biochem Mol Biol. ;35:709-719.

Abraham EG., Islam S., Srinivasan P., Ghosh AK., Valenzuela JG., Ribeiro LMC., Kafatos FC., Dimopoulos, G. and Jacobs-Lorena M. (2004) Analysis of the Plasmodium and Anopheles transcriptional repertoire during ookinete development and midgut invasion. J Biol Chem. 279: 5573-5580.

Srinivasan P., Abraham EG., Ghosh AK., Valenzuela J., Ribeiro JMC., Dimopoulos, G., Kafatos FC., Adams JH., Fujioka J and Jacobs-Lorena M. (2004) Analysis of The Plasmodium and ANOPHELES transcriptomes during oocyst differentiation. J Biol Chem. 279: 5581-5587.

Wu MH, Dimopoulos G, Mantalaris A, Varley J. (2003) The effect of hyperosmotic pressure on the antibody production and gene expression of GS-NS0 cell line. Biotechnol Appl Biochem. Nov 13.

Kumar S., Christophides GK., Cantera R., Charles B., Soon HY., Meister P., Dimopoulos, G., Kafatos FC., Barillas-Mury C. (2003) The role of Reactive Oxygen Species (ROS) on Plasmodium melanotic encapsulation in Anophele gambiae. Proc. Natl. Acad. Sci. USA. 100: 14139- 14144.

Dessens, JT., Sidén-Kiamos, I., Jmendoza, J., Mahairaki, V., Khater, E., Vlachou, D., Xu, JX., Kafatos, FC., Louis, C., Dimopoulos, G. and Sinden, RE. (2003) SOAP, a novel malaria ookinete protein involved in mosquito midgut invasion and oocyst development. Mol Microbiol. 49:319-329.

Dimopoulos, G. (2003) Insect immunity and its implication in mosquito-malaria interactions. Microreview Cell Microbiol.5: 3-14.

Christophides GK, Zdobnov E, Barillas-Mury C, Birney E, Blandin S, Blass C, Brey PT, Collins FH, Danielli A, Dimopoulos G, et al., (2002) Immunity-related genes and gene families in Anopheles gambiae. Science 298:159-165.

Zdobnov EM, von Mering C, Letunic I, Torrents D, Suyama M, Copley RR, Christophides GK, Thomasova D, Holt RA, Subramanian GM, Mueller HM, Dimopoulos G, etal., (2002) Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster. Science 298: 149-159.

Dimopoulos, G., Christophides GK., Meister S., Schultz J., White KP., Barillas-Mury C.and Kafatos FC. (2002) Genome expression analysis of Anopheles gambiae: Responses to injury, bacterial challenge and malaria infection. Proc. Natl. Acad. Sci. USA. 99:8814-8819.

Zhang, D., Dimopoulos, G., Wolf, A., Minana, B., Kafatos, F.C. and Winzerling, J. (2002) Cloning and molecular characterization of two mosquito iron regulatory protein 1 genes. Insect Biochem Mol Biol. 32, 579-589.

Dimopoulos, G., Kafatos F.C., Waters A.P., Sinden R.E. (2002) Malaria Parasites and the Anopheles Mosquito. in Chemical Immunology Vol. 80 „Malaria Immunology“ 2nd ,pp. 27-49.

Viziol, J., Bulet, P., Hoffmann, J.A., Kafatos, F.C., Müller, H-M and Dimopoulos, G. (2001) Gambicin: a novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae. Proc Natl Acad Sci U S A 98:12630-12635.

Dimopoulos, G., Müller, H-M, Levashina, E.A. and F.C. Kafatos (2001) Innate immune defense against malaria infection in the mosquito. Curr. Opin. Immunol. 13, 79-88.

Dimopoulos, G., Casavant, L., Chang, S., Scheetz, T., Roberts, C., Donohue, M., Schultz, J., Benes, V., Bork, P., Ansorge, W., Soares, B. and Kafatos, F. C. (2000) Anopheles gambie pilot gene discovery project: Identification of novel mosquito innate immunity genes from ESTs generated from immune competent cell lines. Proc. Natl. Acad. Sci. USA 97, 6619-6624.

Dessens, J.T., Beetsma, A.L., Dimopoulos, G., Wengelnik, K., Crisanti, A., Kafatos, F.C. and Sinden, R.E. (1999). CTPR is essential for mosquito infection by malaria ookinetes. EMBO J. 18, 6221-6227.

Müller, H.-M., Dimopoulos, G., Blass, C. and Kafatos, F.C. (1999) A hemocyte-like cell line established from the malaria vector Anopheles gambiae expresses six prophenoloxidase genes. J. Biol. Chem., 274, 11727-11735.

Arcà, B., Lombardo, F., de Lara Capurro Guimarães, M., della Torre, A., Dimopoulos, G., James. A. A. and Coluzzi, M. (1999) Trapping cDNAs encoding secreted proteins from the salivary glands of the malaria vector Anopheles gambiae. Proc. Natl. Acad. Sci. USA 96, 1516-1521.

Shen, Z., Dimopoulos, G., Kafatos, F.C. and Jacobs-Lorena, M. (1999) A cell surface mucin specifically expressed in the midgut of the malaria mosquito Anopheles gambiae. Proc. Natl. Acad. Sci. USA, 96, 6510-5615.

Dimopoulos, G., Seeley, D., Wolf A. and Kafatos, F. C. (1998) Malaria infection of the mosquito Anopheles gambiae activates immune responsive genes during critical transition stages of the parasite life cycle. EMBO J. 17, 6115-6123.

Richman, A., Dimopoulos, G., Seeley, D. and Kafatos, F. C. (1997) Plasmodium activates the innate immune response of Anopheles gambiae mosquitoes. EMBO J. 16, 6114-6119.

Dimopoulos, G., Richman, A., Müller, H.-M. and Kafatos, F. C. (1997) Molecular immune responses of the mosquito Anopheles gambiae to bacteria and malaria parasites. Proc. Natl. Acad. Sci. USA, 94, 11508-11513.

Dimopoulos, G., Richman, A., della Torre, A., Kafatos, F. C., and Louis, C. (1996) Identifiation and characterization of differentially expressed cDNAs of the vector mosquito, Anopheles gambiae. Proc. Natl. Acad. Sci USA, 93, 13066-13071.

Dimopoulos, G., della Torre, A., Kumar, V., Kafatos, F. C., and Louis, C. (1996) Integrated Genetic Map of Anopheles gambiae: use of RAPD Polymorphisms for Genetic, Cytogenetic and STS landmarks. Genetics, 143, 953-960.

Favia, G., Dimopoulos, G., della Torre, A., Toure', Y. T., Coluzzi, M., and Louis, C. (1994) Polymorphisms detected by random PCR distinguish between different chromosomal forms of Anopheles gambiae. Proc. Natl. Acad. Sci. USA 91, 10315-10319.

Favia G, Dimopoulos G, Louis C. (1994) Analysis of the Anopheles gambiae genome using RAPD markers. Insect Mol Biol. 3: 149-157.