SITE MENU

FACULTY MENU

picture of Anthony A. James
 Anthony A. James

University of California

Dept. Molec. Biol. Biochem.
McGaugh Hall 3205
Mail Code: 3900
Irvine, CA 92697

PHONE: (949) 824-5930
FAX: (949) 824-2814

E-MAIL: aajames@uci.edu

 

Anthony A. James
Distinguished Professor, Microbiology & Molecular Genetics
School of Medicine
Distinguished Professor, Molecular Biology and Biochemistry
School of Biological Sciences

PH.D., University of California, Irvine

Research Interests
Molecular biology of insect vectors of disease, genetics of vector competence, malaria, dengue fever.

Faculty/lab web:
http://www.microbiology.uci.edu/
Faculty/lab web:
http://mbb.bio.uci.edu/home.html
 
Graduate Programs:
Immunology and Pathogenesis Biotechnology
 
Professional Society 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
 
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 have started experiments that will investigate the second major research area, the movement of laboratory-developed, pathogen-resistance genes into wild populations of mosquitoes. We have planned a number of experiments that will test the mobility of genes in caged populations of mosquitoes. These experiments should give us an indication of what will be needed to drive introduced genes in a safe and effective manner through target populations. This work is being explored firts with the vectors of dengue viruses. The laboratory also has researched malaria parasite development in the mosquito. Our efforts have identified genes whose products may be therapeutic or vaccine targets.


Other Experience
Updated: Last Updated: 06/03/2014

  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.

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.

FACULTY