Michael Gale, Jr. , PhD
Professor, Immunology
Adjunct Professor, Microbiology:
and Global Health
Affiliate Investigator, Clinical Research Division
Fred Hutchinson Cancer Research Center

Department of Immunology
University of Washington
Office H 466 HSC, Box 357650
1959 NE Pacific Street
Seattle, WA 98195-7650
Tel: 206.543-8514
Fax: 206.543-1013
Email: mgale@u.washington.edu

Gale Lab Contacts
Gale Lab Website

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.

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.

Research Centers and Associated Programs:
Center for the Study of Immune Mechanisms of Flavivirus Control
Hepatitis C Cooperative Research Center
Pacific Northwest Regional Center of Excellence
Innate Immune Adjuvant Discovery
Hepatitis C virus (HCV)
West Nile virus (WNV)
Human Immunodeficiency virus (HIV)

Hepatitis C virus. Hepatitis C virus mediates chronic infection in 2% of the world population, and is a major etiology of liver disease; infection is treated through injection of alpha interferon. Our studies are currently focused on defining the processes by which hepatitis C virus suppresses innate immunity and interferon actions to persist in the infected cell.

West Nile virus. West Nile virus has emerged across the Western hemisphere and North America. Our studies utilize in vitro systems and transgenic mouse models to determine the West Nile virus/host interactions that modulate innate immunity and the outcome of infection.

Human Immunodeficiency virus (HIV). AIDS is a global public health problem directly linked to immune regulation and immune cell depletion by HIV. Our studies are centered on defining the processes of innate immune governance in T cells and their control by HIV.

Innate immune signaling and the actions of alpha/beta interferons. The Gale laboratory is engaged in ongoing studies to define the molecular mechanisms of innate immune signaling actions of RIG-I, MDA5, and other PRR pathways that regulate immunity against RNA virus infection. These studies include a specific focus to define viral PAMPs and their signaling factors of immune stimulation, determine the interferon-stimulate genes and their actions in innate immune programs that control infection, and identifying virus/host processes whose actions can be targeted through novel therapeutic strategies to enhance immunity to infection.

Students training in the Gale Lab: John Errett, Amina Negash, Olivia Perwitasari (MCB), Arjun Rustagi (MSTP)

Selected publications:
Luke et al. (2010) Coexpressed RIG-I Agonist Enhances Humoral Immune Response to Influenza DNA Vaccine. J. Virol. IN PRESS. PMID: 21106745

Daffis et al. (2010) 2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature. 18:452-456. PMID: 21085181

Malathi et al. (2010) RNase L releases a small RNA from HCV RNA that refolds into a potent PAMP. RNA. 16:2108-2119. PMID: 20833746

Suthar et al. (2010) IPS-1 is essential for the control of West nile virus infection and immunity. PLoS Pathogens. 6:e1000757. PMID: 20140199

Yuan et al. (2010) Evolution of hepatitis C virus NS5A region in breakthrough patients during pegylated interferon and ribavirin therapy*. J Viral Hepat. 17:208-216. PMID: 19656286.

Wilkins et al. (2010) Recognition of viruses by cytoplasmic sensors. Curr Opin Immunol. 22:41-47. PMID: 20061127.

Owen et al. (2009) Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor. Virology. 394:99-108. PMID: 19751943.

Doehle et al. (2009) HIV-1 mediates global disruption of innate antiviral signaling and immune defenses within infected cells. J Virol. 83:10395-10405. PMID: 19706707.

Jain et al. (2009) Pegylated Interferon and Ribavirin Promote Early Evolution of Nonstructural 5A Protein in Individuals with Hepatitis C Who Demonstrate a Response to Treatment. J Infect Dis. 200:866-876. PMID: 19673650.

Lau et al. (2008) Interferon regulatory factor-3 activation, hepatic interferon-stimulated gene expression, and immune cell infiltration in hepatitis C virus patients.. Hepatology. 47:799-809. PMID: 18203148.

Erickson et al. (2008) Antiviral potency analysis and functional comparison of consensus interferon, interferon-alpha2a and pegylated interferon-alpha2b against hepatitis C virus infection. Antivir Ther. 2008;13:851-862. PMID: 19043919.

Saito et al (2008) Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature. 454:523-527. PMID: 18548002.

Loo et al. (2008) Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol. 82:335-345. PMID: 17977974.

Malathi et al. (2007) Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448: 816-819. PMID: 17653195.