Grants and Contracts
The Host Response to Hepatitis C Virus
These studies will complement existing projects in the Gale laboratory that are focused on developing improved HCV culture systems and understanding the role of the viral proteins and host interferon stimulating genes in controlling HCV infection and pathogenesis.
Center for the Study of Innate Immunity to HCV Infection
This center is comprised of experts in the areas of HCV immunobiology, virology, and clinical care; studies are focused on innate immunity, hepatic immunology, and interferon anti-viral therapy to HCV infection. This research will broaden our understanding of the virus/host interactions of Hepatitis C virus (HCV) that regulate innate immunity, therapy, and the outcome of infection.
Center for the Study of Immune Mechanisms of Flavivirus Control
The goal of this research is to define the innate and adaptive immune parameters that control resistance to flavivirus infection. We will apply our findings to vaccine and therapeutic design to enhance immunity to WNV infection; and to extend to vaccine design against Dengue virus.
Innate Immune Control of West Nile Virus
The goal of this research is define the virus and host processes that control WNV infection and immunity, through understanding the dual role of RIG-I an dMDA5 in restricting WNV infection; identifying the PAMPS within the WNV RNA that are recognized by RIG-I and MDA 5; defining the IFN
RIG-I-Like Receptors and Novel Innate Immune Pathways for Adjuvant Discovery and Development
This program is focused on discovering and developing small molecule innate immune adjuvants that target either RIG-I-like receptors (RLRs) and pathways or novel innate immune factors and pathways, with the ultimate goal of enhancing immunity against RNA virus infection. By targeting RLRs and their pathways, our goal is to discover and develop adjuvants that override virus countermeasures of RLR signaling; thus serving to stimulate, restore, and enhance innate antiviral immunity against pathogenic RNA viruses. Importantly, these compounds are also likely to display antiviral properties that are independent of an immunogen or vaccination strategy.
Development of KIN-1148 as a Novel Innate Immune Adjuvant System for Emerging RNA Virus Vaccines
This program will develop and optimize KIN-1148, a novel small-molecule adjuvant that acts through the RIG-I pathway and IRF-3 transcription factor to stimulate innate immunity and protection following viral infection. The adjuvant will be developed for an FDA-approved avian inluenza virus vaccine as well as evaluation in flavivirus vaccine platforms, including West Nile virus, because of the small molecules broad immune-enhancing activity.
Agonists of the RIG-I Innate Immune Pathway
This program is further investigating and characterizing lead compound candidates for treatment of infections caused by RNA viruses such as hepatitis C virus (HCV), influenza virus (FLU), and West Nile Virus (WNV). These studies will reveal the molecular mechanism of action and scope of antiviral activity as well as define dose tolerability for further commercial development.
Innate Immune Antivirals for Biodefense
The goal of this project is to identify, characterize and develop effective antiviral immunotherapeutics that target novel innate immune signaling pathways to potentially enhance immunity to control infections caused by Category A, B and C agents. Specifically, our program is designed to advance the development of 2 lead candidate compounds as immunotherapeutics against West Nile virus, Dengue, Ebola, and Nipah viruses.
Systems Immunogenetics of Biodefense Pathogens in the Collaborative Cross
The primary objective of this Program is to use genetically diverse mouse models as discovery platforms to identify novel genes and expression networks that regulate immunity and/or promote protective or pathogenic immune outcomes following infection. Our long-term goal is to develop new, genetically defined mouse models to mechanistically dissect the role of specific polymorphic genes and sets of genes in differentially regulating targeted immune respopnses; including crosstalk between immune components and the development of protective or pathogenic immune responses following virus infection.
Regional Center of Excellence for Biodefense and Emerging Infectious Diseases
This Center brings together a consortium of investigators with extensive expertise and basic and translational research capacity. The information gathered by this Center will facilitate development of next-generation therapeutics, diagnostics, and vaccine against Category A-C Pathogens. The Gale lab is especially interested in defining and characterizing innate immune programs for the treatment of infection by West Nile virus.
Innate Immune Defense Against HCV and HIV: The Chimeric Mouse Model
This project aims to define the molecular processes, and identify novel therapeutic targets, within the virus/host interface that regulate the host response to HCV and control infection outcome in a chimerical mouse model in vivo system. The project is also focused on defining the innate immune correlated that regulate HIV infection in vitro and to develop a dual infection model in the chimeric mouse in vivo.