Department of Immunology

Michael Gale Jr., PhD

PROFESSOR, IMMUNOLOGY; ADJUNCT PROFESSOR, MICROBIOLOGY & GLOBAL HEALTH; MEMBER, FHCRC/UW CANCER CONSORTIUM; AFFILIATE INVESTIGATOR, CLINICAL RESEARCH DIV.& VIRUS AND INFECTIOUS DISEASE DIV., FHCRC; DIRECTOR, CENTER FOR INNATE IMMUNITY & IMMUNE DISEASE

Dr. Michael Gale, Jr. received his training at the University of Washington School of Public Health and Community Medicine. He served on the faculty of the University of Texas Southwestern Medical Center until joining the University of Washington in 2007.

CONTACT INFO

Department of Immunology
University of Washington
Office E383, Box 358059
750 Republican Street
Seattle WA 981909-4766
Phone: 206-543-8514
Fax: 206-616-4274

RESEARCH AREAS

Molecular Immunology
Innate Immunity

LAB MEMBERS

Current lab members.

LAB

Website for the Gale Laboratory

Center for Innate
Immunity and Immune
Disease (CIIID)

PUBMED

Michael Gale, Jr., Ph.D.

RESEARCH

Research in the Gale laboratory is focused on understanding innate immunity to virus infection, and the intracellular immune processes and virus-host interactions that govern viral replication and infection outcome. The laboratory is a component of the Hepatitis C virus Cooperative Research Centers supported by the NIH. Additionally, the Gale laboratory has research programs focused on understanding immune control of West Nile virus infection, HIV infection, and the immunomodulatory/antiviral actions of interferons and small molecule inhibitors of virus replication.

Virus infection of mammalian cells triggers an intracellular immune response, termed the “innate immune response” that functions to suppress replication and spread of the virus. During infection specific motifs within viral products are recognized as pathogen associated molecular patterns (PAMPs) by cellular factors called pathogen recognition receptors (PRRs). Studies in the Gale laboratory have defined the retinoic acid-inducible gene I (RIG-I) as the major PRR that triggers immunity against hepatitis C virus and a variety of pathogenic RNA viruses. Accumulating evidence now indicates that immunity against RNA viruses is largely triggered through the PRR actions of RIG-I and/or a related protein called MDA5. RIG-I and MDA5 are cytosolic RNA helicase and are expressed at a low levels in most cells. During virus infection RIG-I or MDA5 bind to RNA PAMP motifs of viral genome or viral RNA replication products generated by specific viruses. RIG-I binding of viral RNA triggers its downstream signaling to induce the activation of latent transcription factors and the eventual production of alpha/beta interferons and expression of interferon-stimulated genes. These processes induce the innate immune response that serves to limit virus replication and spread. Many viruses direct actions of immune evasion through regulation of innate immune signaling and function. Our studies have linked the course of virus infection to regulation of innate immune processes, and have identified novel interactions as therapeutic targets for the intervention of infection.

PUBLICATIONS

  1. Wilkins, C., Woodward, J., Lau, D.T., Barnes, A., Joyce, M., McFarlane, N., McKeating, J.A., Tyrrell, D.L., Gale, M. Jr. (2013) IFITM1 is a tight junction protein that inhibits hepatitis C virus entry. Hepatology. 57:461-469. PMID: 22996292 PMCID: PMC3566288
  2. Wollish, A.C., Ferris, M.T., Blevins, L.K., Loo, Y-M., Gale, M. Jr. Heise, M.T. (2013) An attenuating mutation in a neurovirulent Sindbis virus strain interacts with the IPS-1 signaling pathway in vivo. Virology. 435:269-280. PMID: 23084425. PMCID: PMC3534923
  3. Lau, D.T., Negash, A., Chen, J., Crochet, N., Sinha, M., Zhang, Y., Guedj, J., Holder, S., Saito, T., Lemon, S.M., Luxon, B.A., Perelson, A.S., Gale, M. Jr. (2013) Innate immune tolerance and the role of kupffer cells in differential responses to interferon therapy among patients with HCV genotype 1 infection. Gastroenterology. 144:402-413. PMID: 23123437
  4. Mateo, R., Nagamine, C.M., Spagnolo, J., Mendez, E., Rahe, M., Gale, M. Jr., Yuan, J., Kirkegaard, K. (2013) Inhibition of cellular autophagy deranges dengue virion maturation. J Virol. 87:1312-1321. PMID: 23175363. PMCID: PMC3554187
  5. Ramos, H.J., Lanteri, M.C., Blahnik, G., Negash, A., Suthar, M.S., Brassil, M.M., Sodhi, K., Treuting, P.M., Busch, M.O., Norris, P.J., Gale, M. Jr. (2013) IL-1b signaling promotes CNS-intrinsic immune control of West Nile virus infection. PLoS Pathog. 8(11):e1003039. PMID: 23209411 PMCID: PMC3510243
  6. Lazear, H.M., Lancaster, A., Wilkins, C., Suthar, M.S., Huang, A., Vick, S.C., Clepper, L., Thackray, L., Brassil, M.M., Virgin, H.W., Nikolich-Zugich, J., Moses, A.V., Gale, M. Jr., Früh, K., Diamond, M.S. (2013) IRF-3, IRF-5, and IRF-7 Coordinately Regulate the Type I IFN Response in Myeloid Dendritic Cells Downstream of MAVS Signaling. PLoS Pathog. 9:e1003118. PMCID: PMC3536698
  7. Ma, D.Y., Suthar, M.S., Kasahara, S., Gale, M. Jr., Clark, E.A. (2013) CD22 is required for protection against West Nile Virus infection. J Virol. 87:3361-3375. PMCID: PMC3592166
  8. Kumar, M., Roe, K., Orillo, B., Muruve, D.A., Nerurkar, V.R., Gale, M. Jr., Verma, S. (2013) Inflammasome adaptor protein apoptosis-associated speck-like protein containing CARD (ASC) is critical for the immune response and survival in West Nile virus encephalitis. J Virol. 87:3655-3667 PMCID: PMC3624239
  9. Suthar, M.S., Diamond, M.S., Gale, M. Jr. (2013) West Nile virus infection and immunity. Nat Rev Microbiol. 11:115-128. PMID: 23321534
  10. Wilkins, C., Gale, M. Jr. (2013) Sterol-izing Innate Immunity. Immunity. 38:3-5. PMID: 23352217
  11. Ermler, M.E., Yerukhim, E., Schriewer, J., Schattgen, S., Traylor, Z., Wespiser, A.R., Caffrey, D.R., Chen, Z.J., King, C.H., Gale, M. Jr., Colonna, M., Fitzgerald, K.A., Buller, R.M., Hise, A.G. (2013) RNA helicase signaling is critical for type I interferon production and protection against Rift Valley Fever virus during mucosal challenge. J Virol.87:4846-4860. PMCID: PMC3624317
  12. Cho, H., Proll, S.C., Szretter, K.J., Katze, M.G., Gale, M. Jr., Diamond, M.S. (2013) Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses. Nat Med 19:458-464. PMCID:3618596
  13. 13.   Suthar, M.S., Brassil, M.M., Blahnik, G., McMillan, A., Ramos, H.J., Proll, S.C., Belisle, S.E., Katze, M.G., Gale, M. Jr. (2013) A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes. PLoS Pathog. 9:e1003168. PMCID:3567171
  14. Negash, A.A., Ramos, H.J., Crochet, N., Lau, D.T., Doehle, B., Papic, N., Delker, D.A., Bertoletti, A., Hagedorn, C.H., Gale, M. Jr. (2013) IL-1β Production through the NLRP2 Inflammasome by Hepatic Macrophages Links Hepatitis C Virus Infection with Liver Inflammation and Disease. PLoS PAthog. 9:e1003330. PMCID: PMC3635973
  15. Stone, A.E., Giugliano, S., Schnell, G., Cheng, L., Leahy, K.F., Golden-Mason, L., Gale, M. Jr., Rosen, H.R. (2013) Hepatitis C Virus Pathogen Associated Molecular Pattern (PAMP) Triggers Production of Lambda-Interferons by Human Plasmacytoid Dendritic Cells. PLoS Pathog. 9:e1003316. PMCID: PMC3630164
  16. Li, J., Ding, S.C., Cho, H., Chung, B.C., Gale, M. Jr., Chanda, S.K., Diamond, M.S. (2013) A short hairpin RNA screen of interferon-stimulated genes identifies a novel negative regulator of the cellular antiviral response. MBio. 4(3):1-11. PMCID: PMC3684836
  17. Horner, S.M., Gale, M. Jr. (2013) Regulation of hepatic innate immunity by hepatitis C virus. Nat Med. 19(7):879-888. PMID: 23836238
  18. Lazear, H.M., Pinto, A.K., Ramos, H.J., Vick, S.C., Shrestha, B., Suthar, M.S., Gale, M. Jr., Diamond, M.S. (2013) The pattern recognition receptor MDA5 modulates CD8+ T cell-dependent clearance of West Nile virus from the central nervous system. J Virol. IN PRESS PMID: 23966390
  19. Errett, J.S., Suthar, M.S., McMillan, A., Diamond, M.S., Gale, M. Jr. (2013) The essential, non-redundant roles of RIG-I and MDA5 in detecting and controlling West Nile virus infection. J Virol. IN PRESS. PMID: 23966395