Anthony A. James

picture of Anthony A. James

Donald Bren Professor, Microbiology & Molecular Genetics
School of Medicine
Donald Bren Professor, Molecular Biology and Biochemistry
School of Biological Sciences

PH.D., University of California, Irvine

Phone: (949) 824-5930
Fax: (949) 824-2814

University of California, Irvine
Dept. Molec. Biol. Biochem.
McGaugh Hall 3205
Mail Code: 3900
Irvine, CA 92697
Research Interests
Molecular biology of insect vectors of disease, genetics of vector competence, malaria, dengue fever.
Academic Distinctions
Fellow of the Royal Entomological Society, 1992; Burroughs-Wellcome Award in Molecular Parasitology, 1994; Fellow of the American Association for the Advancement of Science,1994; Burroughs-Wellcome Fund New Initiatives in Malaria Research Award,2000; Foreign Fellowship,Japan Society for the Promotion of Science, 2003; Distinguished Alumnus, School of Biological Sciences, University of California, Irvine, 2004; Member National Academy of Sciences USA, 2006; Distinguished Professor, 2007; Recipient of a MERIT Award, National Institutes of Health 2007; Co-recipient of the Premio de Investgación Médica Dr. Jorge Rosenkranz, 2008; UCI Medal, 2009; Recipient of the Entomological Society of America (ESA); 2009 Nan-Yao Su Award for Innovation and Creativity in Entomology; Fellow of the Entomological Society of America, 2011;Fellow of the American Society of Tropical Medicine and Hygiene, 2012; Recipient of the Athalie Clarke Achievement Award for Outstanding Research, University of California, Irvine, School of Medicine 2013; Rosetta B. Barton Lecturer, University of Oklahoma 2013.
Research Abstract
Mosquitoes are arguably the most dangerous animals in the world. Annual human mortality from malaria transmitted by just one species, Anopheles gambiae, exceeds two million, while Aedes aegypti transmits viral diseases such as dengue and yellow fever. While these diseases occur principally in tropical zones, emerging pathogens such as Chikungunya and West Nile viruses may represent future medical and public health threats in more temperate regions. The goal of our laboratory is to develop novel, genetics-based control methods for blocking transmission of human pathogens by mosquitoes. The hypothesis driving our efforts is that the introduction into a population of mosquitoes of a gene that confers resistance to a pathogen should lead to a decrease in transmission of that pathogen. Implicit in this hypothesis is the assumption that less transmission will result in less disease and death. To test this hypothesis, a gene or allele that interferes with pathogen development or propagation must be discovered or developed, and subsequently spread through a mosquito population. Following implementation of this strategy, there should be measurable decreases in incidence and prevalence of the targeted disease.

Research in three areas needs to be done to test the hypothesis. First, we must develop mosquitoes that are resistant to pathogens. Second, we must develop procedures for moving genes developed in the laboratory into wild mosquito populations. Finally, we must have sufficient information about the target mosquito population so that we can model and predict how the gene will behave in the population. This is important for both the introduction of the gene and establishing parameters by which the success of the introduction will be measured.

In parallel lines of research, we are evaluating the genetic control hypothesis using mosquitoes that have been engineered to be resistant to the pathogens that cause malaria or dengue fever. Our research group has focused first on the laboratory component of this strategy and we identified three research goals that must be met in order to make pathogen-resistant mosquitoes. The first goal was to identify as a target of intervention a tissue in which specific interactions occur between the pathogens and host mosquitoes. Our approach has been to isolate and characterize genes expressed specifically in that tissue, and use the control DNA sequences of these genes to express a coding region that will confer resistance to the pathogens. Our second goal was to develop transgenesis technology that would allow the introduction into the genome of mosquitoes a gene or genes capable of interfering with pathogen development. Our final goal was to develop a hybrid gene that interferes with pathogen development when expressed in the mosquito. This will be the gene that is spread through a target population and is expected to affect pathogen transmission. Our laboratory has had much success with these goals using avian malaria as a model. We are working now with the most lethal human malaria parasite, Plasmodium falciparum. Most recently, we have partnered with a network of laboratory and field scientists and modellers to develop genetic control approaches for preventing the transmission of dengue viruses.

Recently we started experiments that investigate the second major research area, the movement of laboratory-developed, pathogen-resistance genes into wild populations of mosquitoes. In collaboration with Valentino Gantz and Ethan Bier (University of California, San Diego), we developed a highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi. This specific system results in progeny of males and females derived from transgenic males exhibiting a high frequency of germ-line gene conversion consistent with homology-directed repair (HDR). This system copies an ~17-kb construct from its site of insertion to its homologous chromosome in a faithful, site-specific manner. Dual anti-Plasmodium falciparum effector genes, a marker gene, and the autonomous gene-drive components are introgressed into ~99.5% of the progeny following outcrosses of transgenic lines to wild-type mosquitoes. The effector genes remain transcriptionally inducible upon blood feeding. Strains based on this technology could sustain control and elimination as part of the malaria eradication agenda.
Zhang, Z., Niu, B., Ji, D., Li, M., Li, K., James, A.A., Tan, A. and Huang, Y. (2018) Silkworm genetic sexing through W chromosome-linked, targeted gene integration. Proc. Natl. Acad. Sci. USA Aug 13. pii: 201810945. doi: 10.1073/pnas.1810945115. [Epub ahead of print] PMID:30104361.
Bottino-Rojas, V., Talyuli, O.A.C., Carrara, L., Martins, A.J., James, A.A., Oliveira, P.L. and Paiva-Silva, G.O. (2018) The redox-sensing gene Nrf2 affects intestinal homeostasis, insecticide resistance and Zika virus susceptibility in the mosquito Aedes aegypti. J Biol Chem. doi: 10.1074/jbc.RA117.001589. PMID:29685890.
Li, Z., You, L., Yan, D., James, A.A., Huang, Y. and Tan, A. (2018) Bombyx mori histone methyltransferase BmAsh2 is essential for silkworm piRNA-mediated sex determination. PLoS Genet. Feb 23;14(2):e1007245. doi: 10.1371/journal.pgen.1007245. [Epub ahead of print] PMID:29474354.
Yen, P.S., James, A.A., Chen, C.H. and Failloux, A.B. (2018) Synthetic miRNAs induce dual arboviral-resistance phenotypes in the vector mosquito, Aedes aegypti. Communications Biol. 1, 11. doi:10.1038/s42003-017-0011-5
Carballar-Lejarazú, R. and James, A.A. (2018) Population modification of Anopheline species to control malaria transmission. Pathog Glob Health. Feb 1:1-12. doi: 10.1080/20477724.2018.1427192. [Epub ahead of print] PMID:29385893.
Macias, V.M., Jimenez, A.J., Burini-Kojin, B., Pledger, D., Jasinskiene, N., Phong, C.H., Chu, K., Fazekas, A., Martin, K., Marinotti, O. and James, A.A. (2017) nanos-driven expression of piggyBac transposase induces mobilization of a synthetic autonomous transposon in the malaria vector mosquito, Anopheles stephensi. Insect Biochem. Molec. Biol. 87: 81-89. PMID:28676355.
Gonzalez-Lopez, L., Arrevillaga Boni, G., Carballar-Lejarazu, R., Cortes Martinez, L., Cazares-Raga, F.E., Rodriguez, M.H., James, A.A., and de la Cruz Hernandez-Hernandez, F. (2017) Lys48 ubiquitination during the intraerythrocytic cycle of the rodent malaria parasite, Plasmodium chabaudi. PloS ONE 12(6):e0176533. PMID:28604779
Chen, S., Hou, C., Bi, H., Wang, Y., Xu, J., Li, M., James, A.A., Huang, Y. and Tan, A. (2017) Transgenic CRISPR/Cas9-mediated viral gene targeting for antiviral therapy of Bombyx mori nucleopolyhedrovirus (BmNPV). J Virol. 91(8). PMID: 28122981.
Xu, J., Zhan, S., Chen, S., Zeng, B., Li, Z., James, A.A., Tan, A. and Huang, Y. (2016) Sexually dimorphic traits in the silkworm, Bombyx mori, are regulated by doublesex. Insect Biochem Mol Biol. 80:42-51. PMID: 27867075.
Peng, Z., Caihe, L., Beckett, A.N., Guan, Q., James, A.A. and Simons, F.E. (2016) rAed a 4: A new 67-kDa Aedes aegypti mosquito salivary allergen for the diagnosis of mosquito allergy. Int Arch Allergy Immunol. 170: 206-210. PMID: 27603527.
Liu, H., Liu, T., Xie, L., Wang, X., Deng, Y., Chen, C.H., James, A.A. and Chen, X. G. (2016) Functional analysis of Orco and odorant receptors in odor recognition in Aedes albopictus. Parasit Vectors 9: 363. PMID: 27350348.
Huang, Y., Chen, Y., Zeng, B., Wang, Y., James, A.A., Gurr, G.M., Yang, G., Lin, X., Huang, Y. and You, M. (2016) CRISPR/Cas9 mediated knockout of the abdominal-A homeotic gene in the global pest, diamondback moth (Plutella xylostella). Insect Biochem Mol Biol. 75: 98-106.PMID: 27318252.
Carballar-Lejarazú, R., Brennock, P. and James AA. (2016) Suppressor of hairy-wing, modifier of mdg4 and centrosomal protein of 190 gene orthologues of the gypsy insulator complex in the malaria mosquito, Anopheles stephensi. Insect Mol Biol. 25: 460-469.PMID: 2711089.
Kojin, B., Costa-da-Silva, A., Maciel, C., Henriques, D., Carvalho, D., Martin, K., Marinotti, O., James, A., Bonaldo, M. and Capurro, M. (2016) Endogenously-expressed NH2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands. Malaria J. 15:153 PMID: 26964736
Gantz, V. M., Jasinskiene, N., Tatarenkova, O., Fazekas, A., Macias, V. M., Bier, E. and James, A. A. (2015) Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito, Anopheles stephensi. Proc.Natl. Acad. Sci. USA 112(49):E6736-43: PMID:26598698.
Chen, X.G., Jiang, X., Gu, J., Xu, M., Wu, Y., Deng, Y., Zhang, C., Bonizzon,i M., Dermauw, W., Vontas, J., Armbruster, P., Huang, X., Yang, Y., Zhang, H., He, W., Peng, H., Liu, Y., Wu, K., Chen, J., Lirakis, M., Topalis, P., Van Leeuwen, T., Hal,l A.B., Jiang, X., Thorpe, C., Mueller, R.L., Sun, C., Waterhouse, R.M., Yan, G., Tu, Z.J., Fang, X. and James AA. (2015) Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution. Proc Natl Acad Sci U S A. 112(44):E5907-15. PMID:26483478
Brown, D.M., Alphey, L.S., McKemey, A., Beech, C., and James, A.A. (2014) Criteria for identifying and evaluating candidate sites for open-field trials of genetically-engineered mosquitoes. Vector Borne Zoo. Dis., 14, 291-299. PMID: 24689963
Franz, A.W.E., Sanchez-Vargas, I., Raban, R.R., Black, W.C., James, A.A. and Olson, K.E. (2014) Fitness impact and stability of a transgene conferring resistance to dengue-2 virus following introgression into a genetically-diverse Aedes aegypti strain. PLoS NTD 8 (5): e2833. PMID: 24810399
Chagas, A.C., Ramirez, J.L., Jasinskiene, N., James, A.A. Ribeiro, J.M.C., Marinotti, O. and Calvo, E. (2014) The collagen-binding protein, Aegyptin, regulates probing time and blood feeding success in the dengue vector mosquito, Aedes aegypti. Proc. Natl. Acad. Sci. USA 111 6946-6951. PMID: 24778255
Marinotti, O., Ngo, T., Burini-Kojin, B., Chou, S., Nguyen, B., Juhn, J., Carballar-Lejarazú, Marinotti, P., Jiang, X, Walter, M., Tu, Z., Gershon, P.D. and James, A.A. (2014) Integrated proteomic and transcriptomic analysis of the Aedes aegypti eggshell. BMC Developmental Biology 14 (1) 15. PMID: 24707823
Ramsey, J.M., Bond, J.G., Macotela, M.E., Facchinelli, L., Valerio, L. Brown, D.M., Scott, T.W. and James, A.A. (2014) A regulatory structure for working with genetically-modified mosquitoes: Lessons from Mexico. PLoS Negl Trop Dis 8(3): e2623. doi:10.1371/journal.pntd.0002623
Li, J., Wang, X., Zhang, G., Githure, J.I., Yan, G. and James, A.A. (2013) Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae. Proc. Natl. Acad. Sci. USA 110, 20675-20680.
Bonizzoni, M., Gasperi, G., Chen, X. and James, A.A. (2013) The invasive mosquito species Aedes albopictus: current knowledge and future perspectives. Trends Parasitol. 29: 460-468. PMID: 23916878.
DeGennaro, M., McBride, C.S., Seeholzer, L., Nakagawa, T., Dennis, E.J., Goldman, C., Jasinskiene, N., James, A.A. and Vosshall, L.B. (2013) orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET. Nature 2013 May 29. doi: 10.1038/nature12206. [Epub ahead of print]
Marinotti, O, Jasinskiene, N., Fazekas, A., Scaife, S., Fu, G., Mattingly, S.T., Chow, K, Brown, D.M. and James, A.A. (2013) Development of a population suppression strain of the human malaria vector mosquito, Anopheles stephensi. Malaria Journal 26, 142.
Carballar-Lejarazú, R., Jasinskiene, N. and James, A.A. (2013) Exogenous gypsy insulator sequences modulate transgene expression in the malaria vector mosquito, Anopheles stephensi. PNAS, 110, 7176-7181.
Facchinelli, L., Valerio, L., Ramsey, J.M., Gould, F., Walsh, R.K., Bond, G., Robert, M.A., Lloyd, A.L., James, A.A., Alphey, L. and Scott, T.W. (2013) Field cage studies and progressive evaluation of genetically-engineered mosquitoes. PLoS Negl Trop Dis 7(1): e2001. doi:10.1371/journal.pntd.0002001
Bonizzoni, M., Dunn , W. A., Campbell, C.L., Olson, K.E., Marinotti, O. and James, A.A. (2012) Complex modulation of the Aedes aegypti transcriptome in response to dengue virus infection. PLoS ONE 7(11): e50512. doi:10.1371/journal.pone.0050512
Isaacs, A.T., Jasinskiene, N., Tretiakov, M., Thiery, I., Zettor, Agnes, Bourgouin, C. and James, A.A. (2012) Transgenic Anopheles stephensi co-expressing single-chain antibodies resist Plasmodium falciparum development. Proc. Natl. Acad. Sci. USA, 109, E1922-E1930. PMID:22689959. PNAS PLUS , 109, 11070-11071.
Bonizzoni, M., Dunn, W.A., Campbell, C.L. Olson, K.E., Marinotti, O. and James, A.A. (2012) Strain variation in the transcriptome of the dengue fever vector, Aedes aegypti. Genes, Genomes and Genetics 2, 103-114. PMID:22384387.
Ecology. Mosquito trials.
James S, Simmons CP, James AA.
Science. 2011 Nov 11;334(6057):771-2. No abstract available.
Safety of genetically modified mosquitoes.
Benedict MQ, James AA, Collins FH.
JAMA. 2011 May 25;305(20):2069-70; author reply 2070. No abstract available.
Engineered resistance to Plasmodium falciparum development in transgenic Anopheles stephensi.
Isaacs AT, Li F, Jasinskiene N, Chen X, Nirmala X, Marinotti O, Vinetz JM, James AA.
PLoS Pathog. 2011 Apr;7(4):e1002017. Epub 2011 Apr 21.
Peng, Z., Xu, W.W., Sham, Y., Lam, H., Sun, D., Li, C., Rasic, N.F., Guan, Q., James, A.A. and Simons, F.E.R. (2015) Mosquito salivary allergen Aed a 3: cloning, comprehensive molecular analysis, and clinical evaluation. Allergy Nov 26. doi: 10.1111/all.12812. [Epub ahead of print] PMID: 26608594.
Bonizzoni, M., Gasperi, G., Chen, X. and James, A.A. (2013) The invasive mosquito species Aedes albopictus: current knowledge and future perspectives. Trends Parasitol. 29: 460-468. PMID: 23916878.
Wise de Valdez, M.R., Nimmo, D., Betz, J., Gong, H-F., James, A.A., Alphey, L. and Black IV, W.C. (2011) Genetic elimination of dengue vector mosquitoes. Proc. Natl. Acad. Sci. USA, 108, 4772-4775. PMID:21383140
Bonizzoni, M., Dunn, W.A., Campbell, C.L., Olson, K.E., Dimon, M.T., Marinotti O. and James, A.A. (2011) RNA-seq analyses of blood-induced changes in gene expression in the mosquito vector species, Aedes aegypti. BMC Genomics 12, 82. PMID: 21276245: PMCID: PMC3042412
Mathur, G., Sanchez-Vargas, I., Alvarez, D., Olson, K.E., Marinotti, O. and James, A.A. (2010) Transgene-mediated suppression of dengue viruses in the salivary glands of the yellow fever mosquito, Aedes aegypti. Insect Mol Biol. 19, 753-763. PMID: 20738425 PMCID: PMC2976824
Dissanayake, S.N., Ribeiro, J.M.C., Wang, M-H., Dunn, W.A., Yan, G., James, A.A. and Marinotti, O. (2010) aeGEPUCI: a database of gene expression in the dengue vector mosquito, Aedes aegypti. BMC Research Notes 3, 248. PMID: 20920356 PMCID: PMC2958886
Lavery, J.V., Tinadana, P.O, Scott, T.W., Harrington, L.C., Ramsey, J. M., Ytuarte-Nuñez, C. and James, A.A. (2010) Towards a framework for community engagement in global health research. Trends in Parasitology 26, 279-283. PMID: 20299285
Fu, G., Lees, R., Aw, D., Jin, L., Gray, P., Berendonk, T.U, White-Cooper, H., Scaife, S., Phuc, H.K., Marinotti, O., Jasinskiene, N., Nimmo, D., James, A.A. and Alphey, L. (2010) Female-specific flightless phenotype for mosquito control. Proc. Natl. Acad. Sci. USA 107, 4550-4554
Beaty, B.J., Prager, D.J., James, A.A., Jacobs-Lorena, M., Miller, L.H., Law, J.H., Collins, F.C. and Kafatos, F.C. (2009) From Tucson to Genomics and Transgenics: The Vector Biology Network and the Emergence of Modern Vector Biology. PLoS Negl Trop Dis 3, e343. doi:10.1371/journal.pntd.0000343
Adelman, Z.N., Jasinskiene, N., Onal, S., Juhn, J., Ashikyan, A., Salampessy, M., MacCauley and James, A.A. (2007) nanos gene control DNA mediates developmentally-regulated transposition in the yellow fever mosquito, Aedes aegypti. Proc. Natl. Acad. Sci. USA 104, 9970-9975
Jasinskiene, N., Coleman, J., Ashikyan, A., Salampessy, M., Marinotti, O. and James, A.A. (2007) Genetic control of malaria parasite transmission: threshold levels for infection in an avian model system. Am. J. Trop. Med. Hygiene 76, 1072-1078.
Franz, A.W.E., Sanchez-Vargas, I., Adelman, Z N., Blair, C.D., Beaty, B.J., James, A.A. and Olson, K.E. (2006) Engineering RNA interference-based resistance to dengue virus type-2 in genetically-modified Aedes aegypti. Proc. Natl. Acad. Sci USA 103, 4198-4203.
Marinotti, O., Calvo, E., Nguyen, Q.K., Dissanayake, S., Ribeiro, J.M.C. and James, A.A. (2006) Genome-wide analysis of gene expression in adult Anopheles gambiae. Insect Molec. Biol. 15, 1-12.
James, A.A. (2005) Gene drive systems in mosquitoes: rules of the road. Trends in Parasitology 21, 64-67.
Xavier, N. and James, A.A. (2003) Engineering Plasmodium-refractory phenotypes in mosquitoes. Trends in Parasitology 19, 384-387.
Professional Societies

American Society of Tropical Medicine and Hygiene

American Association for the Advancement of Science
American Committee on Vector Entomology

Royal Entomological Society
Entomological Society of America
Genetics Society of America
Society of Vector Ecology
Graduate Programs
Immunology and Pathogenesis


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