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Stephen Higgs, B.Sc., Ph.D., F.R.E.S.

Professor, Department of Pathology;
Member, WHO Collaborating Center for Tropical Diseases;
Member, Center for Biodefense & Emerging Infectious Diseases;
Member, Sealy Center for Vaccine Development;
Director, BSL-3 Insectary

University of Texas Medical Branch
301 University Blvd,
Galveston, TX 77555-0609

Office: (409) 747-2426
Fax: (409) 747-2437
Lab (409) 772-2511
sthiggs@utmb.edu

Professional Education

Honors

Professional Affiliations

Research Interests

Viruses that are transmitted by arthropods such as mosquitoes, sand flies, blackflies and ticks cause many diseases in both human and other animal hosts. Many of these diseases are emerging in new areas or resurging in areas from which they were previously eradicated. Many factors contribute to this expansion, for example reduced efforts in mosquito control and more rapid and widespread travel. The introduction of West Nile virus into the US demonstrates how a virus in a new area can quickly establish a life cycle involving locally abundant mosquitoes and vertebrates. Such an event demonstrates the importance of arthropod-borne viruses. Dengue viruses, for example, may infect over 100 million people annually, causing disease and economic losses throughout much of the tropics. Ironically, although these diseases have been studied for many years, many aspects of the diseases and the transmission cycles remain unknown.

My group’s research encompasses many aspects of mosquito-borne viruses, with my particular interests focusing on mosquito-virus-vertebrate interactions. Using wild type and genetically engineered chikungunya, Sindbis, o’nyong nyong, West Nile and yellow fever viruses we have been examining fundamental aspects of virus-vector interactions.

Some of our work has been directed towards the identification of molecular mechanisms that could be used to reduce the efficiency of pathogen transmission. This research is a critical component in the development of novel strategies to reduce the impact of vector-borne diseases. With colleagues at CSU during the 1990s, sequences were identified that prevented transmission of several viruses. A scorpion neurotoxin that might be used for biological control was evaluated and we pioneered the expression of green fluorescent protein in mosquitoes, that has since become a standard marker of mosquito transgenesis and may be used for identification and tracking of genetically engineered arthropods. We collaborate with colleagues at Notre Dame, and other universities with support from the Bill and Melinda Gates Foundation to evaluate the use of transgenic mosquitoes for the control of dengue.

A recent interest has developed from the realization that during biting, an arthropod secretes substances that not only influence pathogen transmission, but also determine the severity of the disease. In collaboration with Dr. Lynn Soong we have identified some of the molecules and mechanisms that are involved in this fascinating phenomenon.

In 2005 we demonstrated direct transmission of West Nile virus from infected to uninfected mosquitoes whilst feeding on an uninfected host. This discovery accelerates the transmission cycle and means that many more vertebrates may be involved in transmission than originally thought.

Our research on chikungunya virus (CHIKV) preceded the ongoing epidemic that has recently infected over 1.4M people. Our development of patented infectious clones of this CHIKV has placed us at the forefront of research on this virus. UTMB encourages collaborative research and we have distributed these research tools to other groups in an effort to better understand the epidemic.

Research facilities at UTMB are second to none, and are continuously being added to. New fully equipped BSL-3 insectaries were completed in 2007, we have core insectary facilities in the Galveston National Laboratory, which opened in 2008, and ultimately will have the capability for BSL-4 research. UTMB has assembled a unique team of faculty that is comprised of the finest researchers anywhere. The opportunity to work with this team has provided an extraordinary academic environment that I believe will allow us to make a difference in the field of arthropod-borne diseases. Recent graduates from my laboratory have been employed at CDC Puerto Rico, the Institute Pasteur, Paris and at UC Berkeley.

Selected Publications

ARTICLES IN PEER-REVIEWED JOURNALS:

1. Higgs, S., Nowell, F. and Ibrahim, S.A.M.  The initiation and maintenance of a colony of coccidia-free wood mice (Apodemus sylvaticus). Lab. Animals. 22: 54-60; 1987. PMID: 2965281
2. Higgs, S. and Nowell, F.  Laboratory studies with clones of Eimeria hungaryensis, a parasite of the wood mouse Apodemus sylvaticus. Parasitology. 97:213-220; 1988. PMID: 3200603
3. Nowell, F. and Higgs, S.  Eimeria species infecting wood mice (genus Apodemus) and the transfer of two species to Mus musculus. Parasitology. 98: 329-336; 1989. PMID: 2528109
4. Gould, E.A., Buckley, A., Cane, P.A., Higgs, S. and Cammack, N.  Use of a monoclonal antibody specific for wild-type yellow fever virus to identify a wild-type antigenic variant in 17D vaccine pools.  J. Gen. Virol. 70:1889-1894; 1989. PMID: 2472467
5. Marriott, A.C., Ward, V.K., Higgs, S. and Nuttall, P.A. RNA probes detect nucleotide sequence homology between members of two different nairovirus subgroups. Virus Res. 16: 77-82; 1990. PMID: 2112292
6. Gould, E.A., Buckley, A., Higgs, S. & Gaidamovich, S.  Antigenicity of flaviviruses. Arch. Virol., Supplementum I: 137-152; 1990.
7. Buckley, A., Higgs, S. & Gould, E.A. Dugbe virus susceptibility to neutralization by monoclonal antibodies as a marker of virulence in mice. Arch. Virol., Supplementum I:197-205; 1990.
8. El-Ghorr, A.A., Marriott, A.C., Ward, V.K., Booth, T.F., Higgs, S., Gould, E.A., & Nuttall, P.A.  Characterization of Dugbe virus by biochemical and immunochemical procedures using monoclonal antibodies. Arch. Virol., Supplementum I: 169-179; 1990.
9. Higgs, S. & Nowell, F. A review of the species of Eimeria infecting hosts in the genus Apodemus. Syst. Parasitol. 20: 203-209; 1991.
10. Higgs, S. & Gould, E.A.  Differences in fusogenicity and mouse neurovirulence of Japanese encephalitis viruses. Arch. Virol. 119: 119-133; 1991. PMID: 1650549
11. Shiu, S.W., Morikawa, S., Buckley, A., Higgs, S., Karunakarannair, V., Blachere, C. & Gould, E.A. 17D yellow fever vaccine virus envelope protein expressed by recombinant baculovirus is antigenically indistinguishable from authentic viral protein. J. Gen. Virol. 72:1451-1454; 1991. PMID: 1710651
12. Jones, L.D., Hodgson, E., Williams, T., Higgs, S. & Nuttall, P.A. Saliva activated transmission (SAT) of Thogoto virus: relationship with vector potential of different haematophagous arthropods. Med. Vet. Entomol. 6: 261-265; 1992. PMID: 1330087
13. Jiang, W.R., Lowe, A., Higgs, S., Reid, H. and Gould, E.A.  Single amino acid codon changes detected in louping ill virus antibody-resistant mutants with reduced neurovirulence. J. Gen. Virol. 74: 931-935; 1993. PMID: 8388021
14. Higgs, S., Powers, A.M., and Olson, K.E.  Alphavirus expression systems: applications to mosquito vector studies. Parasitol. Today. 9: 444-452; 1993. PMID: 15463689
15. Olson, K., Higgs, S., Hahn, C.S., Rice, C.M., Carlson, J.O., & Beaty, B.J. Expression of chloramphenicol acetyltransferase in Aedes albopictus (C6/36) cells and Aedes triseriatus mosquitoes using double subgenomic recombinant Sindbis virus vectors. Insect Biochem. Mol. Biol. 24: 39-48; 1994. PMID: 8111422
16. Powers, A.M., Higgs, S., Olson, K.E., Carlson, J.O., & Beaty, B.J. Interference to La Crosse virus superinfection by an antisense RNA generated from an infectious Sindbis virus vector. Virus Res. 32: 57-67; 1994 PMID: 8030366
17. Carlson, J,. Olson, K., Higgs, S. and Beaty, B.  Molecular genetic manipulation of mosquito vectors. Ann. Rev. Entomol. 40: 359-88; 1995. PMID: 7810990
18. Higgs, S., Olson, K.E., Klimowski, L., Powers, A.M., Carlson, J.O., Possee, R.D. & Beaty, B.J. Mosquito sensitivity to a scorpion neurotoxin expressed using an infectious Sindbis virus vector. Insect Mol. Biol. 4: 97-103; 1995. PMID: 7551198
19. Rayms-Keller, A., Powers, A.M., Higgs, S., Olson, K.E., Kamrud, K.I., Carlson, J.O. & Beaty, B.J. Replication and expression of a recombinant Sindbis virus in mosquitoes. Insect Mol. Biol. 4: 245-251; 1995. PMID: 8825762
20. Kamrud, K.I., Powers, A.M., Higgs, S., Olson, K.E., Blair, C.D., Carlson, J.O. & Beaty, B.J.  The expression of chloramphenicol acetyl transferase in mosquitoes and mosquito cells using a packaged Sindbis replicon system. Exp. Parasitol. 81: 394-403; 1995. PMID: 7498436
21. Powers, A.M., Kamrud, K.I., Olson, K.E., Higgs, S., Carlson, J.O. & Beaty, B.J. Molecularly engineered resistance to California serogroup virus replication in mosquito cells and mosquitoes. PNAS. 93: 4187-4191; 1996. PMID: 8633038
22. Matsubara, T., Beeman, R.W., Besansky, N., Mukabayire, O., Higgs, S. James, A.A. & Burns, J.C. Pantropic retroviral vectors integrate and express in cells of the malaria mosquito, Anopheles gambiae. PNAS. 93: 6181-6185; 1996. PMID: 8650240
23. Gaines, P.J., Olson, K.E., Higgs, S., Powers, A.M., Beaty, B.J. & Blair, C.D.  Pathogen-derived resistance to dengue type 2 virus in mosquito cells by expression of the premembrane coding region of the viral genome. J. Virol.. 70: 2132–2137; 1996. PMID: 8642634
24. Olson, K.E., Higgs, S., Gaines, P.J., Powers, A.M., Davis, B.S., Kamrud, K.I., Carlson, J.O., Blair, C.D. & Beaty, B.J.  Genetically engineered resistance in mosquitoes to dengue virus transmission. Science. 272: 884-886; 1996. PMID: 8629025
25. Higgs, S., Traul, D., Davis, B.S., Kamrud, K.I., Wilcox, C. & Beaty, B.J. Green fluorescent protein expressed in living mosquitoes, without the requirement of transformation. BioTechniques. 21: 660-664; 1996. PMID: 8891217
26. Kamrud, K.I., Olson, K.E., Higgs, S., Powers, A.M., Carlson, J.O. & Beaty, B.J. Detection of chloramphenicol acetyltransferase in the saliva of Culex pipiens mosquitoes. Ins. Biochem. Mol. Biol. 27: 423-429. 1997. PMID: 9219368
27. Higgs, S., Rayner, J., Olson, K., Davis, B.S., Beaty, B.J. & Blair, C.D.  Engineered resistance in Aedes aegypti to a West African and a South American strain of yellow fever virus. Am. J. Trop. Med. Hyg. 58: 663-670; 1998. PMID: 9598458
28. Edwards, J.F., Higgs, S. & Beaty, B.J.  Mosquito feeding-induced potentiation of Cache Valley Virus (Bunyaviridae) in mice. J. Med. Entomol. 35: 261-265; 1998. PMID: 9615544
29. Jordan, T.V., Shike, H., Boulo, V., Cedeno, V., Fang, Q., Davis, B.S., Jacobs-Lorena, M., Higgs, S., Fryxell, K. & Burns, J.C.  Pantropic retroviral vectors mediate somatic cell transformation and expression of foreign genes in Dipteran insects. Insect Mol. Biol. 7: 215-222; 1998. PMID: 9662470
30. Seabaugh, R.C., Olson, K.E., Higgs, S., Carlson, J.O. & Beaty, B.J.  Development of a chimeric Sindbis virus with enhanced Per Os infection of Aedes aegypti. Virology. 243: 99-112; 1998.  PMID: 9527919
31. Kamrud, K.I., Olson, K.E., Higgs, S., Carlson, J.O. & Beaty, B.J.  Use of the Sindbis replicon system for expression of LaCrosse virus envelope proteins in mosquito cells. Arch. Virol. 143: 1365-1377; 1998. PMID: 9722880
32. Zeidner, N.S., Higgs, S., Happ, C.M., Beaty, B.J. & Miller, B.R. Mosquito feeding modulates Th1 and Th2 cytokines in flavivirus susceptible mice: an effect mimicked by injection of sialokinins, but not demonstrated in flavivirus resistant mice. Parasite Immunol. 21: 35-44; 1999. PMID: 10081770
33. Higgs, S., Oray,C.T., Myles, K. Olson, K.E.&  Beaty, B.J.  Infecting Larval Arthropods With a Chimeric Double Subgenomic Sindbis Virus Vector to Express Genes of Interest. BioTechniques. 27: 908-911; 1999.  PMID: 10572634
34. Lewis, D.L., DeCamillis, M.A., Brunetti, C.R., Halder, G., Kassner, V.A., Selegue, J.E., Higgs, S. & Carroll, S.N. Ectopic gene expression in developing butterflies, beetles and other arthropods using recombinant Sindbis virus. Current Biol. 22:1279–1287; 1999. PMID: 10574759
35. Johnson, B.W., Olson, K.E., Allen-Muira, T, Rayms-Keller, A., Carlson, J.O., Coates, C.J., Jasinskiene, N.J., James, A.A., Beaty, B.J. & Higgs, S.  Inhibition of luciferase expression in transgenic Aedes aegypti mosquitoes by Sindbis virus expression of antisense luciferase RNA. PNAS. 96: 13399–13403; 1999. PMID: 10557332
36. Graham, D.H., Holmes, J.L., Higgs, S., Beaty, B.J. & Black, W.C. IV.  Selection of refractory and permissive strains of Aedes triseriatus (Diptera: Culicidae) for transovarial transmission of La Crosse virus. J. Med. Entomol. 36: 671–678; 1999. PMID: 10593065
37. Olson, K.E., Myles, K., Seabaugh, R.C., Higgs, S., Carlson, J.O. & Beaty, B.J. Development of a Sindbis virus expression system that efficiently expresses green fluorescent protein in midguts of Aedes aegypti following per os infection. Insect Mol. Biol. 9: 57–65; 2000. PMID: 10672072
38. Wendell, M.D., Wilson, T.G., Higgs, S. & Black, W.C. IV.  Chemical and gamma-ray mutagenesis of the white gene in Aedes aegypti. Insect Mol. Biol. 9:119-125; 2000. PMID: 10762419
39. Higgs, S. & Nowell, F.  Population biology of Eimeria (Protozoa: Apicomplexa) in the wood mouse Apodemus sylvaticus: a capture/recapture study. Parasitology. 120: 355-363; 2000. PMID: 10811276
40. Limesand, K.H., Higgs, S., Pearson, L.D., & Beaty, B.J.  Potentiation of vesicular stomatitis New Jersey virus infection in mice by mosquito saliva. Parasite Immunol. 22: 461-467; 2000. PMID: 10972853
41. Shiao, S.H., Higgs, S., Adelman, Z., Christensen, B.M., Liu, S.H. & Chen, C.C. Effect of prophenoloxidase expression knockout on the melanization of filarial worms in the mosquito, Armigeres subalbatus. Insect Mol. Biol. 10:315-321. 2001. PMID: 11520354
42. Cheng, L.L., Bartholomay, L.C., Olson, K.E., Lowenberger, C., Viziol, J., Higgs, S., Beaty, B.J. & Christensen, B.M. Characterization of an endogenous gene expressed in Aedes aegypti using an orally infectious recombinant Sindbis virus. J. Insect Sci. (Online journal) 1.10. 14pp. 2001. PMID: 15455070
43. Peloquin, J.J., Miller, T.A. & Higgs, S. Pink Bollworm Larvae Infection with a Double Subgenomic Sindbis (dsSIN) Virus to Express Genes of Interest. J. Cotton Sci. 5:114-120. 2001.
44. Bennett, K.E., Olson, K.E., Munoz, M.L., Fernandez-Sala, I., Farfan, J.A., Higgs, S., Black, W.C. & Beaty, B.J. Variation in vector competence for dengue 2 virus among 24 populations of Aedes aegypti from Mexico and the United States. Am. J. Trop. Med. Hyg. 67: 85-92. 2002. PMID: 12363070
45. Vanlandingham, D.L., Davis, B.S., Lvov, D., Higgs, S., Calisher, C.H., Black, W.C. & Beaty, B.J. Molecular characterization of California serogroup viruses isolated in Russia. Am J. Trop. Med. Hyg. 67: 306 – 309. 2002 PMID: 12408673
46. Beasley, D.W.C., Davis, T.C., Guzman, H., Vanlandingham, D.L., Travassos da Rosa, A.P.A., Parsons, R.E., Higgs, S., Tesh, R.B. & Barrett, A.D.T. Limited evolution of West Nile virus during its southwesterly spread in the United States. Virol.  309: 190-195. 2003 PMID: 12758166
47. Limesand, K.H., Higgs, S., Pearson, L.D. & Beaty, B.J. The effect of mosquito salivary gland treatment on vesicular stomatitis New Jersey virus replication and interferon α/β expression in vitro. J. Med. Entomol. 40: 199-205, 2003. PMID: 12693849
48. Tüzün, E., Scott, B.G., Goluszko, E., Higgs, S. & Christadoss, P. Genetic evidence for involvement of classical complement pathway in induction of experimental autoimmune myasthenia gravis. J. Immunol. 171: 3847-1854, 2003. PMID: 14500686
49. Benedict, M.Q., Tabachnick, W.J. & Higgs, S. Arthropod containment guidelines. Vector-Borne and Zoonotic Diseases. 3: 61–98. 2003
50. Attardo, G., Higgs, S., Klingler, K.A., Vanlandingham, D.L. & Raikhel. A.S. RNAi-mediated knockdown of a GATA factor reveals a molecular mechanism of anautogeny in the yellow fever mosquito, Aedes aegypti. PNAS. 100: 13374-13379. 2003. PMID: 14595016 PMCID: PMC263821
51. Diamond, M.S., Sitati, E.M., Friend, L.D., Higgs, S., Shrestha, B. & Engle, M. A critical role for induced IgM in the protection against West Nile virus infection. J. Exp. Med. 12: 1-11. 2003. PMID: 14662909
52. Higgs, S., Snow, K. & Gould, E.A. The potential for West Nile virus to establish outside of its natural range: a consideration of potential mosquito vectors in the United Kingdom. Trans. Roy. Soc. Trop. Med. Hyg. 98: 82-87. 2004. PMID: 14964806
53. Tüzün, E., Scott, B.G. Yang, H., Wu, B., Goluszko, E., Guigneaux, M., Higgs, S., & Christadoss, P. Circulating Immune Complexes Augment Severity of Antibody Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice1 J. Immunology 172: 5743 – 5752, 2004 PMID: 15100321
54. Lillibridge, K.M., Parsons, R., Randle, Y., Travassos da Rosa, E., Guzman, H., Siirin, M., Wuithiranyagool, T., Hailey, C., Beasley, D.W., Higgs, S., Pascual, R., Meyer, T., Barrett, A.D.T. & Tesh, R.B. The 2002 introduction of West Nile virus into Harris County, Texas, an area historically endemic for St. Louis encephalitis. Am. J. Trop. Med. Hyg. 70: 676-681. 2004 PMID: 15211013
55. Vanlandingham, D.L., Schneider, B.S., Klingler, K., Fair, J., Beasley, D., Huang, J,M Hamilton, P., & Higgs, S. Real-time RT-PCR quantification of West Nile virus transmitted by Culex pipiens quinquefasciatus. Am. J. Trop. Med. Hyg. 71: 120-123. 2004 PMID: 15238700
56. Girard, Y.A., Klingler, K.A. & Higgs, S. West Nile virus dissemination and tissue tropisms in orally-infected Culex pipiens quinquefasciatus. Vector-borne & Zoonotic Diseases. 4: 109-122. 2004 PMID: 15228811
57. Wanasen, N., Nussenzveig, R.H., Champagne, D.E., Soong, L. & Higgs, S. Differential modulation of murine host immune response by salivary gland extracts from the mosquitoes Aedes aegypti and Culex quinquefasciatus Med. Vet. Entomol. 2004. 18: 191-199. 2004 PMID: 15189245
58. Mutebi, J-P, Gianella, A., Travassos, A., Tesh, R.B., Barrett, A.D.T. & Higgs, S. Infectivity of yellow fever virus for Bolivian Aedes aegypti mosquitoes. Emerg. Infect. Dis. 10: 1657-1660. 2004 PMID: 15498171
59. Siirin, M., Sargent, C., Langer, R.C., Parsons, R., Vanlandingham, D.L., Higgs, S., &  Tesh, R.B. Comparative Sensitivity of a Wicking Antigen Assay, Reverse Transcriptase-PCR and Direct Culture in Vero Cells for Detection of West Nile Virus in Dead Birds. Vector-borne Zoonotic Dis. 4: 204-209. 2004 PMID: 15631064
60. Tesh, R.B.Parsons, R. Randle, Y., Sargent, C.,Siirin, M., Wuithiranyagool, T., Guzman, H., Higgs, S., Vanlandingham, D.L., Bala, A.A., Haas, K., & Zerinque, B. Evidence of Year-Round West Nile Virus Activity in the Gulf Coast Region of Texas and Louisiana. Emerg. Infect. Dis. 10: 1649-1652. 2004 PMID: 15498169
61. Granwehr, B.P., Lillibridge, K.M., Higgs, S., Mason, P.W., Aronson, J.F., Campbell, G.A., & Barrett, A.D.T. West Nile Virus: Where are we now? Lancet Infect. Dis. 4: 547 -556. 2004 PMID: 15336221
62. Scholle, F., Girard, Y.A., Zhao, Q., Higgs, S., & Mason, P.W. trans-packaged West Nile virus-like particles: infectious properties in vitro and in orally infected mosquito hosts. J. Virol. 78: 11605-11614. 2004 PMID: 15479801 PMCID: PMC523254
63. Infanger, L-C., Rocheleau,T.A., Bartholomay, L.C.,  Johnson, J.K., Fuchs, J., Higgs, S., Chen, C-C., &  Christensen, B.M. The role of phenylalanine hydroxylase in melanotic encapsulation of filarial worms in two species of mosquito. IBMB 34: 1329-1338. 2004. PMID: 15544946
64. Tamang, D., Tseng, S.M., Huang, C.Y., Tsao, I.Y., Chou, S.Z., Higgs, S., Christensen, B.M., & Chen, C.C. The use of a double subgenomic Sindbis virus expression system to study mosquito gene function: effects of antisense nucleotide number and duration of viral infection on gene silencing efficiency. Ins. Mol. Biol. 13: 595-602. 2004 PMID: 15606808
65. Brault, A.C., Foy, B.D., Myles, K.M., Kelly, C.L.H., Higgs, S., Weaver, S.C., Olson, K.E., Miller, B.R., Powers, A.M. Infection patterns of O’nyong nyong virus in the malaria-transmitting mosquito, Anopheles gambiae. Insect. Mol. Biol. 13: 625-635. 2004 PMID: 15606811
66. Schneider, BS, L Soong, NS Zeidner, Higgs, S.. Aedes aegypti Salivary Gland Extracts Modulate Anti-Viral and TH1/TH2 Cytokine Responses to Sindbis Virus Infection. Vir. Immunol. 17: 565-573. 2004. PMID: 15671753
67. Sbrana, E., Tonry, J.H., Xiao, S-Y., Travassos da Rosa, A.P.A., Higgs, S. and  Tesh, R.B. Oral transmission of West Nile virus in a hamster model. Am. J. Trop. Med. Hyg. 72: 325-329. 2005. PMID: 15772330
68. Girard, Y.A., Popov, V., Wen, J., Ham, V. and Higgs, S. Ultrastructural study of West Nile virus pathogenesis in Culex pipiens quinquefasciatus (Diptera: Culicidae). J. Med. Entomol. 42: 429-444. 2005 PMID: 15962797
69. McElroy, K.L., Tsetsarkin, K.A., Vanlandingham, D.L. & Higgs, S. Characterization of yellow fever virus-mosquito interactions using an infectious clone of the wild-type Asibi virus. J. Gen. Virol.  86: 1747-1751. 2005. PMID: 15914853
70. Bryant, J.E., Vasconcelos, P.F.C., Rijnbrand, R.C.A., Mutebi, J.P., Higgs, S. & Barrett, A.D.T. Size heterogeneity in the 3’ noncoding region of south American isolates of yellow fever virus. J. Virol. 79: 3807-3821. 2005. PMID: 15731274
71. Vanlandingham, D.L., Hong, C., Tsetsarkin, K., McElroy, K.L., Powers, A.M., Lehane, M. & Higgs, S. Differential infectivities of o’nyong-nyong and chikungunya viruses in Anopheles gambiae and Aedes aegypti mosquitoes. Am. J. Trop. Med. Hyg. 72: 616-621. 2005 PMID: 15891138
72. Higgs, S., Schneider, B.S., Vanlandingham, D.L., Klingler, K. & Gould, E.A. Non-viremic transmission of West Nile virus. PNAS 102: 8871-8874. 2005. PMID: 15951417 PMCID: PMC1157059
73. Vanlandingham, D.L., Tsetsarkin, T., Hong, C., Klingler, K., Lehane, M.J. and Higgs, S. Development and characterization of a double subgenomic chikungunya virus infectious clone to express heterologous genes in Aedes aegypti mosquitoes. Ins. Biochem. Mol. Biol. 35: 1162-1170. 2005. PMID: 16102421
74. Beasley, D.W.C., Whiteman, M.C., Zhang, S., Huang, C-Y.H.,Schneider, B.S.,Smith, D.R.,  Gromowski, G.D.,  Higgs, S., Kinney, R.M. and ADT Barrett. Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains. J. Virol. 79: 8339-8347. 2005. PMID: 15956579
75. Sim, C., Hong, Y.S., Vanlandingham, D.L., Christophides, G.K., Kafatos, F.C., Higgs, S. & Collins, F.H. Modulation of Anopheles gambiae gene expression in response to o’nyong nyong virus infection. Ins. Mol. Biol. 14: 475-481. 2005. PMID: 16164603
76. Eappen, G.A., Pinto, S.B., Ghosh, A., Vanlandingham, D.L., Budd, A., Higgs, S., Kafatos, F.C., Jacobs-Lorena, M. & Michel, K. An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites. PNAS. 102: 16327-16332. 2005. PMID: 16260729 PMCID: PMC1283470
77. Alto, B.W., Lounibos, L.P., Higgs, S. & Juliano, S.A. Larval competition differentially affects arbovirus infection and dissemination in mosquitoes Aedes albopictus and Aedes aegypti. Ecology. 86: 3279-3288. 2005. PMID: 19096729  PMCID: PMC2605070     
78. Schneider, B.S., Soong, Girard, Y.A., Campbell, G., Mason, P. and Higgs, S.  Potentiation of West Nile Encephalitis by mosquito feeding.  Viral Immunology. 19: 74-82. 2006. PMID: 16553552
79. Higgs, S. A novel method of West Nile virus transmission. Contagion. 3: 95-97.
80. Vanlandingham, D.L., Tsetsarkin, K., Klingler, K.A., Hong, C., McElroy, K.L., Lehane, M.J., Higgs, S. Determinants of vector specificity of o’nyong nyong and chikungunya viruses in Anopheles and Aedes mosquitoes. Am. J. Trop. Med. Hyg. 74: 663-669. 2006 PMID: 16607002
81. Wicker, J.A., Whiteman, M.C., Beasley, D.W., Davis, C.T., Zhang, S., Schneider, B.S., Higgs, S., Kinney, R.M. & Barrett, A.D. A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice. Virology. 349: 245-53. 2006. PMID: 16624366
82. Gould, E.A., Higgs, S., Buckley, A. & Gritsun, T. The risk of arbovirus emergence in the UK. Emerg. Infect. Dis. 12: 549-555. 2006. PMID: 16704800
83. McElroy, K.L., Tsetsarkin, K., Vanlandingham, D.L. and Higgs, S.  Role of the Yellow Fever Virus Structural Protein Genes in Viral Dissemination from the Aedes aegypti Mosquito Midgut J.Gen.Virol. 87: 2993-3001 2006 PMID: 16963758
84. Higgs, S., Vanlandingham, D.L., Klingler, K.A., McElroy, K.L., McGee, C.E., Harrington, L., Lang, J., Monath, T.P. and Guirakhoo, F. Growth characteristics of ChimeriVax-DEN vaccine viruses in Aedes aegypti and Aedes albopictus from Thailand. Am. J. Trop. Med. Hyg. 75: 1158-1164 2006. PMID: 17124001
85. Tsetsarkin, T., Higgs, S., McGee, C.E., de Lamballerie, X., Charrel, R.N. & Vanlandingham, D.L. Infectious Clones of Chikungunya Virus (La Réunion Isolate) for Vector Competence Studies Vector-Borne and Zoonotic Diseases 6: 325-337 2006. PMID: 17187566
86. McElroy, K.L., Tsetsarkin, K., Vanlandingham, D.L. and Higgs, S. Manipulation of the yellow fever   virus non-structural genes 2A and 4B and the 3'non-coding region to evaluate genetic determinants    of viral dissemination from the Aedes aegypti midgut. Am. J. Trop. Med. Hyg. 75, 1158-1164. 2006. PMID: 17172386
87. Tüzün, E., Saini, S.S., Yang, H., Alagappan, D., Higgs, S., & Christadoss, P. Genetic evidence for the involvement of Fcgamma receptor III in experimental autoimmune myasthenia gravis pathogenesis.J Neuroimmunol. 2006 174: 157-67. Epub 2006 Mar 9. PMID: 16527362
88. Girard, Y., Schneider, B.S., McGee, C., Wen, J., Han, V., Popov, V., Mason, P., Higgs, S. Salivary gland morphology and virus transmission during long-term cytopathological West Nile virus infection in Culex mosquitoes. Am. J. Trop. Med. Hyg. 76: 118-128. 2007. PMID: 17255239
89. 88. McGee, C.E., Schneider, B.S., Girard, Y.A., Vanlandingham, D.L., & Higgs, S. Nonviremic transmission of West Nile virus: evaluation of the effects of space, time and mosquito species. Am.J. Trop. Med. Hyg. 76: 424-430. 2007. PMID: 17360862
90. Sim C, Hong YSH, Tsetsarkin K, Vanlandingham DL, Higgs S, Collins FH: Anopheles gambiae Hsc70-4 impedes o’nyong-nyong virus replication. BMC Genomics 8: 231-243 2007. PMID: 17625007 PMCID: PMC1963456
91. Vanlandingham, D.L., McGee, C.E., Klingler, K.A., Vessey, N., Fredregill, C. & Higgs, S. Relative susceptibilities of South Texas mosquitoes to West Nile virus. Am. J. Trop. Med. Hyg. 77: 925-928 2007. PMID: 1798435
92. Schneider, B.S., McGee, C.E., Jordan, J.M., Stevenson, H.L., Soong, L. & Higgs, S. Prior exposure to uninfected mosquitoes enhances mortality in naturally-transmitted West Nile virus infection. PLoS ONE 2(11): e1171. doi:10.1371/journal.pone.0001171. PMID: 18000543
93. Yang,H., Wu,B., Tüzün,E., Saini,S.S., Li,J., Allman, W., Higgs, S., Xiao,T.L. & Christadoss, P., A new mouse model of autoimmune ocular myasthenia gravis. Investigative Ophthalmology and Visual Sciences 48: 5101-5111 2007. PMID: 17962462
94. Tsetsarkin, K.A., Vanlandingham, D.L., McGee., C.E. & Higgs, S. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS PATHOGENS 3(12): e201. doi:10.1371/journal.ppat.0030201 2007. PMID: 18069894 PMCID: PMC2134949
95. McGee, C.E.,Tsetsarkin, K., Vanlandingham, D.L., McElroy, K.L., Lang, J., Guy, B., Decelle, T. & Higgs, S. Substitution of wild-type yellow fever Asibi sequences for homologous 17D vaccine sequences in ChimeriVaxTM-Dengue 4 does not enhance infection of Aedes aegypti mosquitoes. Journal of Infectious Diseases 197: 686-692. 2008. PMID: 18266608 PMCID: PMC2597369
96. McGee, C.E., Lewis, M.G., St. Claire, M., Wagner, W., Lang, J., Guy, B., Tsetsarkin, K., Higgs, S. & Decelle, T. Recombinant ChimeriVaxTM dengue 4 with virulent yellow fever Asibi backbone sequences is dramatically attenuated in non-human primates. Journal of Infectious Diseases 197: 693-697. 2008. PMID: 18266603
97. De-Lamballerie, X., Leroy, E., Charrel, R.N., Tsetsarkin, K., Higgs, S. & Gould, E.A. Chikungunya Virus Adapts to Tiger Mosquito via Evolutionary Convergence: a Sign of Things to Come? Virology Journal 2008, 5:33doi:10.1186/1743-422X-5-33. 2008. PMID: 18304328 PMCID: PMC2266737
98. Schneider, B.S. and Higgs, S. The enhancement of arbovirus transmission and disease by mosquito saliva is associated with modulation of the host immune response. Trans. Roy. Soc. Trop. Med. Hyg. 102: 400-408. 2008. PMID: 18342898 PMCID: PMC2561286
99. Benedict, M., D’Abbs, P., Dobson, S., Gottlieb, M., Harrington, L., Higgs, S., James, A., James, S., Knols, B., Lavery, J., O’Neill, S., Scott, T., Takken, W. & Toure Y. Guidance for Contained Field Trials of Vector Mosquitoes Engineered to Contain a Gene Drive System: Recommendations of a Scientific Working Group. Vector- Borne and Zoonotic Diseases 8: 127-166. 2008. PMID: 18452399
100. McElroy, K.L., Girard, Y.A., McGee., C.E., Tsetsarkin, K.A., Vanlandingham, D.L. & Higgs, S. Characterization of the Antigen Distribution and Tissue Tropisms of Three Phenotypically Distinct Yellow Fever Virus Variants in Orally Infected Aedes aegypti Mosquitoes. Vector-Borne and Zoonotic Diseases 8: 675-87. 2008. PMID: 18494601
101. May, F.J., Li, L., Zhang, S., Guzman, H., Beasley, D.W.C., Tesh, R.B., Higgs, S., Raj, P., Bueno Jr, R., Randle, Y., Chandler, C. & Barrett, A.D.T. Genetic variation of St Louis encephalitis virus. J. Gen Virology 89: 1901-1910. 2008. PMID: 18632961
102. Kato, N., Mueller, C.R., Fuchs, J.F., McElroy, K., Wessely, V., Higgs, S. & Christensen, B.M. Biological characterization of the type I peritrophic matrix in Aedes aegypti: effect of peritrophic matrix thickness on pathogen development, protein digestion and fecundity. Vector- Borne and Zoonotic Diseases 8: 701-12. 2008. PMID: 18627241
103. Guy ,B., Guirakhoo, F., Watson, M., Higgs, S., & Monath, T.P. Safety of flavivirus chimeric vaccines: answer to Ishikawa et al. [Vaccine 26 (22) (2008) 2772-2781]. Vaccine. 2008 Aug 5;26(33):4107-8. Epub 2008 Jun 9. PMID: 18573573
104. Vanlandingham, D.L., McGee, C.E., Klingler, K., Galbraith, S. A., Barrett, A.D.T., Higgs, S. Comparison of oral infectious dose of West Nile virus isolates representing three distinct genotypes in Culex pipiens quinquefasciatus. Trop Med Hyg. 79: 951-954. 2008. PMID 19052310 PMCID: PMC2699256
105. Gould, E.A. & Higgs, S. Impact of climate change and other factors on emerging arbovirus diseases. Trans R. Soc. Trop. Med. Hyg. 103: 109-121 2009. PMID: 18799177
106. McGee, C.E., Shustov, A.V., Tsetsarkin, K., Frolov, I.V., Mason, P.W., Vanlandingham, D.L & Higgs, S. Infection, Dissemination, and Transmission of a West Nile virus Green Fluorescent Protein Infectious Clone by Culex pipiens quinquefasciatus Mosquitoes. Vector- Borne and Zoonotic Diseases. 10: 267-274. 2010. PMID: 19619041
107. Nawtaisong, P., Keith, J., Fraser, T., Balaraman, V., Kolokoltsov, A., Davey ,R.A., Higgs, S., Mohammed, A., Yupha, R., Komalamisra, N. & Fraser, M.J. Effective suppression of Dengue Fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome. Virology Journal 2009, 6: 73 (4 June 2009) PMID: 19497123
108. Tsetsarkin, K., McGee, C., Volk, S., Vanlandingham, D., Weaver, S. & Higgs, S. Epistatic roles of E2 glycoprotein mutations in adaptation of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes. PloS.ONE 4(8): e6835. doi:10.1371/journal.pone.0006835 PMID: 19718263 PMCID: PMC2729410
109. Solignat, M., Gay B., Higgs, S., Briant, L. & Devaux, C. Replication cycle of Chikungunya: a reemerging arbovirus. Virology 393: 183-197. 2009. PMID: 19732931 PMCID: PMC2915564
110. Guy, B., Guirakhoo, F., Barban, V., Higgs, S., Monath, T.P. & Lang, J. Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses. Vaccine. 28: 632-49. 2010.  PMID: 17124001
111. Schilte, C., Couderc, T., Chretien, F., Sourisseau, M., Gangneux, N., Guivel-Benhassine, F., Kraxner, A., Tschopp, J., Higgs, S., Michault, A., Arenzana-Seisdedos, F., Colonna, M., Peduto, L., Schwartz, O., Lecuit, M. & Albert, A.L.  Type I IFN controls chikungunya virus via its action on non-hematopoietic cells. J. Exp. Medicine. 207: 429-442. 2010. PMID: 20123960
112. Akahara, W., Yang, Z., Andersen, H., Sun, S., Yoder, J.D., Kong, W.-P., Lewis, M., Higgs, S., Rossmann, M.G., Rao, S., et al. 2010. A VLP vaccine for epidemic chikungunya virus protects non-human primates against infection. Nature Medicine. 16: 334-8 2010. PMID: 20111039 http://www.nature.com/nm/journal/vaop/ncurrent/pdf/nm.2105.pdf
113. Higgs, S. & Ziegler, S. Chikungunya: A Non-human Primate Model to Evaluate the Basis of Human Disease Symptoms. J. Clinical Invest. 120: 657-660. PMID: 20179348
114. Girard, YA., Mayhew, G.F., Fuchs, J.F., Schneider, B.S., Li, H., Rocheleau, R.A., Christensen, B.M., Higgs, S. & Bartholomay, L.C. Transcriptome changes in Culex quinquefasciatus salivary glands during West Nile virus infection  J. Med Entomol. 47:421-435. 2010. PMID: 20496590
115. Skalsky, R.L., Vanlandingham, D.L., Scholle, F., Higgs S. & Cullen, B.R. Identification of microRNAs expressed in two mosquito vectors, Aedes albopictus and Culex quinquefasciatus. BMC Genomics. Feb 18;11(1):119. [Epub ahead of print] 2010 PMID: 20167119 PMCID: PMC2834634
116. Volk, S.M., Chen, R., Tsetsarkin, K.A., Adams, A.P., Garcia, T.I., Sall, A.A.,  Nasar, F., Schuh, A.J., Holmes, E.C., Higgs, S, A., Maharaj, P.D., Brault.C. & Weaver, S.C. Genome scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and varying evolutionary rates. J. Virol. 84: 6497-504. 2010 PMID: 20410280
117. Gardner, J., Anraku, I., Le, T.T., Larcher, T., Major, L., Roques, P., Schroder, W.A., Higgs, S. & Suhrbier, A. Chikungunya virus arthritis in adult wild-type mice. J. Virol. 84: 8021-32. PMID: 20519386
118. Bernard, E., Solignat, M., Gay, B., Chazal, N., Higgs, S., Devaux, C & Briant, L. Endocytosis of chikungunya virus into mammalian cells: a role of clathrin and early endosomal compartments. PloSOne 5: e11479 (July 2010). PMID: 20628602 PMCID: PMC Journal” – In Process
119. Schneider, B.S., Soong, L., Coffey, L.A., Stevenson, H.L. & Higgs, S. Aedes aegypti Saliva Alters Leukocyte Recruitment and Cytokine Signaling by Antigen-Presenting Cells during West Nile Virus Infection. PloSONE 5: e11704 (July 2010). PMID: 20661470 PMCID:PMC Journal In Process

BOOK CHAPTERS

1. Woodring, J., Higgs, S. & Beaty, B.J.  Natural cycles of vector-borne pathogens. In Biology of Disease Vectors (Marquardt, W.C. & Beaty, B.J. editors). University Press of Colorado, pp 51-72. 1996.
2. Higgs, S. & Beaty, B.J.  Rearing and containment of arthropod vectors. In Biology of Disease Vectors (Marquardt, W.C. & Beaty, B.J. editors). University Press of Colorado, pp 595-605. 1996.
3. Higgs, S., Olson, K.E., Kamrud, K.I., Powers, A.M. & Beaty, B.J.  Viral expression systems and viral infections in insects. In The Molecular Biology of Disease Vectors: A Methods Manual. (Crampton, J.M., Beard, C.B. & Louis, C. editors). Chapman and Hall, UK, pp 457-483. 1997.
4. Carlson, J. O., Afanasiev, B. N., Higgs, S., Matsubara, T. and Burns, J.C.  Viral transducing vectors for mosquitoes. In The Molecular Biology of Disease Vectors: A Methods Manual. (Crampton, J.M., Beard, C.B. & Louis, C. editors). Chapman and Hall, UK, pp 444-458. 1997.
5. Olson, K.E., Beaty, B.J. and Higgs, S. Sindbis virus expression systems for the manipulation of insect vectors. In: The Insect Viruses (L.K. Miller and L.A. Ball, editors). Plenum Publishing Corp, New York. pp 371-404. 1998.
6. Higgs, S. & Lewis, D.L. The green fluorescent protein marker for transgenic insects. In Insect Transgenesis: Methods and Applications. Handler, A.M. & James, A.A. (editors). CRC Press, Boca Raton, Florida. pp 93-108. 2000.
7. Duthu, D.B., Higgs, S., Beets, R.L. & McGlade, T.J. Design issues for insectaries. In Anthology of Biosafety. IV. Issues in Public Health (Richmond, J.Y. editor). Pp 227-244. 2001.
8. Higgs, S., Benedict, M.Q. & Tabachnick, W.J. Arthropod Containment guidelines. In Anthology of Biosafety. VI. Arthropod Borne Diseases. (Richmond, J.Y. editor). Pp 73-84. 2003.
9. Higgs, S., How do mosquito vectors live with their viruses? In: Microbe-Vector Interactions in Vector-Borne Diseases. Gillespie, S.H., Smith, G.L. & Osbourn, A. editors.). Cambridge University Press. pp 103-137. 2004.
10. Higgs, S. & Beaty, B.J. Natural cycles of vector-borne pathogens. Chapter 14 in The Biology of Disease Vectors (Marquardt, W.C., Kondratieff, B., Moore, C.G., Freier, J., Hagedorn, H.H., Black, W. III., James, A.A., Hemingway, J. & Higgs, S. editors). Elsevier Academic Press. pp 167-185. 2004.
11. Higgs, S. The containment of arthropod vectors. Chapter 48 in The Biology of Disease Vectors (Marquardt, W.C., Kondratieff, B., Moore, C.G., Freier, J., Hagedorn, H.H., Black, W. III., James, A.A., Hemingway, J. & Higgs, S. editors). Elsevier Academic Press. 699-704. 2004.
12. Higgs S. Care, maintenance, and experimental infection of mosquitoes.  Chapter 53 in The Biology of Disease Vectors (Marquardt, W.C., Kondratieff, B., Moore. C.G., Freier, J., Hagedorn, H.H., Black, W. III., James, A.A., Hemingway, J. & Higgs, S. editors). Elsevier Academic Press. 733-739. 2004.
13. Barrett, A.D.T. & Higgs, S. Yellow fever: a disease that has yet to be conquered. Annual Review of Entomology. 52: 209-229. 2007. PMID: 16913829
14. Higgs, S. Influences of arthropod vectors on encephalitic arboviruses In: Neurotropic Viral Infections. Cambridge University Press. Pp 362-381. 2008.
15. Higgs, S. Yellow fever. In: Diseases and Disorders (Hildyard, A. & Goddard, J. eds). Marshall Cavendish, Tarrytown, New York. Vol 3. Pp. 899890. 2008.

NIH Biosketch