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Research Focus

Mosquito-borne viruses like Zika, chikungunya, West Nile, St. Louis encephalitis and dengue virus are expanding to cause more human infections worldwide.

Unfortunately, no licensed human vaccines for these viruses are available.

Management of disease is therefore restricted to palliative care for infected people and minimizing exposure to mosquitoes.

Our research  focuses on several central themes with a common goal of reducing the burden of disease caused by arboviruses.

These include:

  • understanding  viral genetic factors that promote arbovirus outbreaks
  • predicting viral mutations that enhance arbovirus transmissibility by mosquitoes and disease in humans or animals
  • increasing safety of candidate live-attenuated vaccines
  • improving arbovirus surveillance in mosquitoes

Current Projects

Current Projects

Safer arbovirus vaccines

In a project funded by the National Institutes of Health NIAID, we are developing safer live attenuated vaccines for chikungunya and Venezuelan equine encephalitis viruses using virus variants that mutate less frequently and therefore develop fewer mutations that confer virulence.

Emerging and re-emerging viruses in California

We are genetically characterizing contemporary West Nile and St. Louis encephalitis virus circulating in mosquitoes in California and performing experimental studies to evaluate viral, host, and environmental factors that promoted the re-emergence of St. Louis encephalitis virus in California in 2015 and 2016 and the maintenance of epidemic West Nile virus each summer.

Non human primate model of Zika virus

Together with the California National Primate Research Center including Koen Van Rompay, we are generating a pregnant macaque model of human Zika virus disease. In addition to using the model to understand human ZIKV infection dynamics and disease with potential effects on fetal development and transfusion transmission, we are testing candidate vaccines and therapies.

  • We partnered with the Food and Drug Administration to investigate which tissues Zika virus targets in non-human primates to inform FDA policies on the risk of Zika virus transmission through infected tissue products.
  • Together with the Blood Systems Research Institute/University of California San Francisco, we are characterizing blood transfusion-transmission of Zika virus in macaques to establish minimal requirements for Zika virus blood or organ transfusion-transmission and to characterize pathogen reduction approaches to interrupt transfusion or organ transmission.
  • We are also developing a project to determine whether mutations in emerging Zika virus are responsible for fetal neurologic disease and death using the macaque model. Defining the viral determinants of clinical Zika virus outcome in macaques could be translated to candidate vaccines or therapies to protect mothers and their infants against the most severe forms of Zika virus disease.

Intrahost genetic diversity and arboviral disease

We are studying how genetically diverse viral populations of chikungunya virus generated by error-prone viral replication influence mosquito-borne virus transmission and disease.

Zika virus vector competence

With funding provided by Abt Associates and the Mosquito and Vector Control Association of California, we are evaluating the capacity of mosquitoes from California to transmit Zika virus. Results from this study will allow prediction of the potential for Zika virus establishment and range expansion in the state.

Enhanced arbovirus surveillance

Together with the Coachella Valley Mosquito and Vector Control District and Sandia National Laboratories, we are developing novel cost-effective approaches to detect arbovirus circulation in mosquitoes in California based on deposition of arbovirus RNA by wild mosquitoes during sugar feeding.

Team

Team

Lark L. Coffey Ph.D., the Principal Investigator, obtained her Ph.D. from the University of Texas Medical Branch. Before joining UC Davis in 2013, she worked at Institut Pasteur, Paris and the Blood Systems Research Institute at the University of California, San Francisco.

lcoffey@ucdavis.edu

Hongwei Liu M.S., Staff Research Associate, received her M.Sc in Genetics from China. She has been working in the field of molecular biology, virology, and immunology for the past 20 years. Her main current focus is to develop an effective live-attenuated vaccine against chikungunya virus infection.

hwlliu@ucdavis.edu

Anil Singapuri M.S., Staff Research Associate, has a Master’s degree from UC Davis in immunology and wrote his thesis on the use of degenerate peptides as vaccines to prevent antigenic escape common in HIV and SIV.  He is currently testing samples from rhesus macaques infected with Zika virus.  Anil is particularly interested Zika virus neurotropism and the potential for the virus to persist in some infected individuals.

singapuri@ucdavis.edu

Danilo Lemos, DVM, UC Davis Ph.D student, obtained his veterinary degree from the Universidade Federal de Campina Grande in Brazil. Danilo is interested in viruses in general. His dissertation is focused on understanding the viral molecular determinants of fetal disease caused by Zika virus rhesus macaques.

dlemos@ucdavis.edu

Jay Nicholson, Ph.D., post-doctoral fellow, obtained his Ph.D. at the University of Queensland, Australia.  He then served as a Laboratory Manager focused on medical entomology and public health related to arbovirus surveillance in Western Australia. Jay is investigating the vector competence of North American mosquitoes for Zika virus.

jnicholson@ucdavis.edu

Brad Main, Ph.D., post-doctoral fellow, has a background in arthropod genomics and transcriptomics. He is passionate about understanding adaptation and speciation and the genetic basis of  insecticide resistance, host preference, and vector competence in mosquitoes. Brad is exploring whether and why distinct genetic populations of Aedes aegypti vary in their ability to become infected by and transmit Zika virus.

bmain@ucdavis.edu

Kasen Riemersma, DVM, UC Davis Ph.D student,  became interested in vector-borne diseases and the complex host-pathogen-environment interactions in veterinary school at the University of Wisconsin. His work with tick-borne Heartland virus at CDC cemented his enthusiasm. His dissertation focuses on how intra-host chikungunya virus diversity affects disease and transmission. His  research interests include arbovirus evolution and emergence, host-virus interactions, and vaccine development.

kkriemersma@ucdavis.edu

Christopher Weiss, Ph.D., Postdoctoral Scholar, received his Ph.D. from the University of Pittsburgh where he studied the molecular basis of alphavirus restriction by an interferon-inducible exonuclease. Chris is interested in rational vaccine design against emerging pathogens and is currently evaluating high-fidelity viral polymerase mutations as a means of improving the safety and efficacy of the live attenuated chikungunya virus vaccine.
 
cmweiss@ucdavis.edu

Cody Steiner B.S. obtained his bachelor’s degree in in Microbiology, Immunology, and Molecular Genetics from UCLA and is currently a UC Davis Ph.D. student in the Epidemiology Graduate Group. He is improving arbovirus surveillance in California by applying molecular diagnostics to novel field surveillance methods and using the results to inform disease models.

cdsteiner@ucdavis.edu

Kelly Symmes, BS., is a third year DVM student at UC Davis interested in zoonoses and public health research. She intends to pursue doctoral work in virology after she obtains her DVM in 2018. Kelly is sequencing West Nile and St. Louis encephalitis virus in California and performing phylogenetic analyses to infer genetic relatedness and origins of circulating viruses.

kpsymmes@ucdavis.edu

Jackson Stuart is a fourth year undergraduate Global Disease Biology major and African History minor at UC Davis focusing on how cultural, historical, and socioeconomic backgrounds of regions influence disease prevalence and interventions. His research focuses on understanding which viral mutations affect chikungunya and Zika virus disease.

jbstuart@ucdavis.edu

Radhika Iyer is a junior undergraduate majoring in Microbiology and minoring in Global Disease Biology at UC Davis. Radhika is interested in pursuing graduate school in virology or infectious disease in the future. She currently works as an Undergraduate Research Assistant and helps with the Zika virus projects.

raiyer@ucdavis.edu

Past Team Members

Kaitlin Xa was a fourth year undergraduate Biochemistry and Molecular Biology major at UC Davis. She is interested in food microbial safety and hopes to enter a food science graduate program in the future. Kaitlin was a student lab assistant in helping with lab maintenance and assistant to our team.

kpxa@ucdavis.edu

Publications

Publications

Complete List in Google Scholar.

Coffey LL, Pesavento PA, Keesler RI, Singapuri A, Watanabe J, Watanabe R, Yee J, Bliss-Moreau E, Cruzen C, Christe KL, Reader JR, von Morgenland W, Gibbons AM, Allen AM, Linnen J, Gao K, Delwart E, Simmons G, Stone M, Lanteri M, Bakkour S, Busch MP, Morrison J, Van Rompay KKA. 2017. Zika virus tissue and blood compartmentalization in acute infection of rhesus macaques. PLoS One. 12(1): e0171148. doi:10.1371/journal.pone.0171148. Link

Stone M, Lantern, MC, Bakkour S, Deng X, Galel SA, Linnen JM, Munoz-Jordan JL, Lanciotti RS, Rios M, Gallian P, Musso D, Levi, JE, Sabino EC, Coffey LL, Busch MP. 2017. Analytical Performance of Donor NAT Screening and Diagnostic Real-Time PCR Assays for Detection of Zika Virus RNA. Transfusion. (57): 734–747. Link.

White, GS, Symmes K, Sun P, Fang Y, Garcia S, Steiner C, Smith K, Reisen WK, Coffey LL. 2016. Reemergence of St. Louis Encephalitis Virus, California, 2015. Emerging Infectious Diseases 22(12):2815-2188. Link.

Ball, CL, Light, Y, Koh, C-Y; Wheeler, S, Coffey, LL; Meagher, R. 2016. Quenching of Unincorporated Amplification Signal Reporters (QUASR) in RT-LAMP Enables Bright, Single-Step, Closed-Tube, and Multiplexed Detection of RNA Viruses. Analytical Chemistry. DOI: 10.1021/acs.analchem.5b04054. Link.

Wheeler SS, Ball CS, Langevin SA Fang Y, Coffey LL, Meagher R. Surveillance for Western Equine Encephalitis, St. Louis Encephalitis, and West Nile Viruses using Reverse Transcription Loop-mediated Isothermal Amplification. 2016. PLoS One, 11(1): e0147962. doi:10.1371/journal.pone.0147962. Link.

Stapleford KA, Coffey LL, Lay S, Duong V, Isakov O, Blanc H, Borderia A, Beaucourt S, Haliloğlu T, Schmitt C, Bonne I, Tal NB, Shomron N, Failloux AB, Buchy P, Vignuzzi M. 2014. Emergence and Transmission of Arbovirus Evolutionary Intermediates with Epidemic Potential. Cell, Host & Microbe, 15:706-716. Link.

Coffey LL, Page BL, Greninger AL, Herring BL, Russell RC, Doggett SL, Haniotis J, Wang C, Deng X, Delwart EL. 2014. Enhanced Arbovirus Surveillance with Deep Sequencing: Identification of Novel Rhabdoviruses and Bunyaviruses in Australian Mosquitoes. Virology Journal, 448:146-158. Link. 

Naccache SN, Greninger AL, Lee D, Coffey LL, Phan T, Rein-Weston A, Aronsohn A, Hackett J Jr, Delwart EL, Chiu CY. 2013.The Perils of Pathogen Discovery: Origin of a Novel Parvovirus-Like Hybrid Genome Traced to Nucleic Acid Extraction Spin Columns. Journal of Virology. 87(22):11966-77. Link.

Berthet N, Paulous S, Coffey LL, Frenkiel MP Moltini I, Tran C, Matheus S, Ottone C, Ungeheuer M-N, Renaudat C, Caro V, Dussart P, Gessain A, Desprès P. 2012. Resequencing Microarray Method for Molecular Diagnosis of Human Arboviral Diseases. Journal of Clinical Virology, 56(3):238-43. Link.

Coffey LL, Beeharry Y, Borderia AV, Blanc H, Vignuzzi M. 2011. Arbovirus High Fidelity Variant Loses Fitness in Mosquitoes and Mice. Proceedings of the National Academy of Sciences, 108(38):16038-43. Link.

Beaucourt S, Borderia AV, Coffey LL, Gnadig NF, Sanz-Ramos M, Beeharry Y, Vignuzzi M. 2011. Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency. Journal of Visualized Experiments, Jun 16;(52) pii:2953. doi:10.3791/2953. Link.

Coffey LL, Vignuzzi M. 2011. Host Alternation of Chikungunya Virus Increases Fitness While Restricting Population Diversity and Adaptability to Novel Selective Pressures. Journal of Virology, 85(2):1025-35. Link.

Schneider BS, Soong L, Coffey LL, Stevenson HL, McGee CE, Higgs S. 2010. Aedes aegypti Saliva Alters Leukocyte Recruitment and Cytokine Signaling by Antigen-Presenting Cells during West Nile Virus Infection. PLOS One, July 22;5(7):e11704. Link.

Coffey LL, Vasilakis N, Brault AC, Powers AM, Tripet F, Weaver SC. 2008. Arbovirus Evolution in vivo is Constrained by Host Alternation. Proceedings of the National Academy of Sciences, 105(19):6970- 6975. Link.

Carrara AC, Coffey LL, Aguilar PV, Moncayo AC, Travassos da Rosa A, Nunes MRT, Tesh RB,Weaver SC. 2007. Venezuelan Equine Encephalitis Virus Infection of Cotton Rats. Emerging Infectious Diseases, 13(8):1158-1165. Link.

Ozden S, Huerre M, Riviere J-P, Coffey LL, Afonso PV, Mouly V, Monredon J, Roger J-C, Amrani M, Yvin J-L, Jaffar M-C, Frenkiel M-P, Sourisseau M, Schwartz O, Butler-Browne G, Desprès P, Gessain A, Ceccaldi P-E. 2007. Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection. PLOS One, Jun 13;2(6):e527. Link.

Coffey LL, Crawford C, Miller R, Dee J, Freier J, Weaver SC. 2006. Serologic Evidence of Widespread Everglades Virus Infection of Dogs in Florida. Emerging Infectious Diseases, 12(12):1873-1879. Link.

Smith DR, Aguilar PV, Coffey LL, Gromowski G, Wang E, Weaver SC. 2006. Estimate of the Amount of Venezuelan Equine Encephalitis Virus Transmitted by Mosquitoes in vivo and the Effect of Transmission Mode on Pathogenesis. Emerging Infectious Diseases, 12(8):1190-1196. Link. 

Navarro JC, Medina G, Vasquez C, Coffey LL, Wang E, Suárez A , Biord H, Salas M, Weaver SC. 2005. Postepizootic Persistence of Venezuelan Equine Encephalitis Virus, Venezuela. Emerging Infectious Diseases, 11(12):1907-1915. Link.

Diallo M, Sall A, Moncayo A, Ba Y, Fernandez Z, Ortiz D, Coffey LL, Mathiot, C, Tesh, RB, Weaver SC. 2005. Potential Role of Sylvatic and Domestic African Mosquito Species in Dengue Emergence. American Journal of Tropical Medicine and Hygiene, 73(2):445-449. Link.

Coffey LL, Weaver SC. 2005. Susceptibility of Ochlerotatus taeniorhynchus and Culex nigripalpus for Everglades Virus. American Journal of Tropical Medicine and Hygiene, 73(1):11-16.

Wang E, Paessler S, Aguilar PV, Smith DR, Coffey LL, Kang W, Pfeffer M, Olson J, Blair PJ, Guevara C, Estrada-Franco J, Weaver SC. 2005. A Novel, Rapid Assay for Detection and Differentiation of Serotype-Specific Antibodies to Venezuelan Equine Encephalitis Complex Alphaviruses. American Journal of Tropical Medicine and Hygiene, 72(6):805-810.

Coffey LL, Carrara AS, Paessler S, Haynie ML, Bradley R, Tesh RB, Weaver SC. 2004. Experimental Everglades Virus Infection of Cotton Rats (Sigmodon hispidus). Emerging Infectious Diseases, 10(12):2182-2188.

Moncayo AC, Fernandez Z, Ortiz D, Diallo M, Sall A, Hartman S, Davis CT, Coffey L, Mathiot CC, Tesh RB, Weaver SC. 2004. Dengue Emergence and Adaptation to Peridomestic Mosquitoes. Emerging Infectious Diseases, 10(10):1790-1797.

Beasley DW, Holbrook MR, Travassos Da Rosa AP, Coffey L, Carrara AS, Phillippi-Falkenstein K, Bohm RP Jr, Ratterree MS, Lillibridge KM, Ludwig GV, Estrada-Franco J, Weaver SC, Tesh RB, Shope RE, Barrett AD. 2004. Use of a Recombinant Envelope Protein Subunit Antigen for Specific Serological Diagnosis of West Nile Virus Infection. Journal of Clinical Microbiology, 42(6):2759-65.

Aguilar PV, Greene IP, Coffey LL, Medina G, Moncayo AC, Anishchenko M, Ludwig GV, Turell MJ, O’Guinn ML, Lee J, Tesh RB, Watts DM, Russell KL, Hice C, Yanoviak S, Morrison AC, Klein TA, Dohm DJ, Guzman H, Travassos da Rosa AP, Guevara C, Kochel T, Olson J, Cabezas C, Weaver SC. 2004. Endemic Venezuelan Equine Encephalitis in Northern Peru. Emerging Infectious Diseases, 10(5):880-8.

Estrada-Franco JG, Navarro-Lopez R, Beasley DW, Coffey L, Carrara AS, Travassos da Rosa A, Clements T, Wang E, Ludwig G, Cortes AC, Ramirez PP, Tesh RB, Barrett AC, Weaver SC. 2003. West Nile Virus in Mexico: Evidence of Widespread Circulation since July 2002. Emerging Infectious Diseases, 9(12):1604-7.

Travassos da Rosa A, Mather T, Takeda T, Whitehouse C, Shope R, Popov V, Guzman H, Coffey L, Araujo T, Tesh RB. 2002. Two New Rhabdoviruses (Rhabdoviridae) Isolated from Birds during Surveillance for Arboviral Encephalitis, Northeastern United States. Emerging Infectious Diseases, 8(6):614-618.

Media

Media

2017

CDC Supports UC Researchers in Fighting Vector-Borne Diseases, University of California, Davis Press Release (Aug 10). View this Article.

Introducing the new Pacific Southwest Regional Center of Excellence in Vector-Borne Diseases. Website

What I Wished I Knew When Starting As a Professor: An Interview with Robert Abramovitch, Lark Coffey, Thomas Kehl-Fie, and Rita Tamayo (July), Cell Press. View this Article. 

2016
Curwin T: How a mosquito bite led to paralysis — and turned this teacher’s life upside down, News Article in Print and Online (Nov 23), LA TimesView this Article

 
Mattson S: Risk of microcephaly discussion after two Zika related microcephaly cases in California, (Aug 5), Bay Area News Group Mercury News.

Koerth-Baker, M: Five Enduring Questions About Zika, News Article, (Aug 3), Five Thirty Eight. View this Article.

Quiros G: How mosquitoes use six needles to suck your blood, Video, KQED Science, (Jun 7). View  Video

 

Mechanic M: Should Americans Be Panicking About Zika?, News Article (May 31), Mother JonesView this Article

 

Dayton J: How to protect yourself from the Zika virus while trying to get pregnant, (May 25, updated Nov 8), Priya Ring BlogView this Article

Staff: Zika virus: emergence, spread, and how to protect yourself from disease, Newspaper Article (Mar 3), Davis High School Newspaper.

Siddiqui F: The talk on Zika, Newspaper Article (Feb 23), The California Aggie NewspaperView this Article

 

Stahler A: RNA viruses and fidelity modulation, Radio Interview (Feb 11), KVMR-FM, Nevada City, CA.

Bailey P: UC Davis Experts on Zika Virus, UC Davis New & Information (Jan 29). View this Article

KCRA News: UCD researchers say Zika cases possible in California, News and Website (Jan 27), KCRAView this Article 

2014
American Society of Tropical Medicine and Hygiene: American Society of Tropical Medicine and Hygiene Member Q & A, American Society of Tropical Medicine and Hygiene Blog.  View this Article