Research Projects

Bacterial Therapeutics

RM RP 001: Immunotherapeutic targets of Francisella tularensis infections

Introduction: The work proposed in the application will demonstrate whether therapeutic vaccination augments standard chemotherapy against an acute bacterial infection and can prevent relapse. Such an approach would have broad implications to the treatment of infections by highly virulent bacterial pathogens.

  • Principal Investigator: John T. Belisle, Ph.D.
  • Institution: Colorado State University, Department of Microbiology, Immunology, and Pathology, Fort Collins, CO
  • Collaborators and Core Labs: Jeannine Petersen, Ph.D., Centers for Disease Control and Prevention, DVBID, Fort Collins, CO

RM RP 002: Combined Immuno-Antimicrobial Therapy for Burkholderia Infection

Introduction: In this proposal we will investigate combined immunotherapy and antimicrobial therapy for treatment of B. pseudomallei infection, with the overall goal of increasing the effectiveness and speed of treatment for both acute and chronic infections. These studies will identify antimicrobials that synergize with anti-bacterial cytokines for eliminating intracellular Burkholderia infection and assess the effectiveness of combined immuno-antimicrobial therapy in vivo, using mouse models of acute and chronic inhaled infection.

  • Principal Investigator: Steven W. Dow, DVM, Ph.D.
  • Institution: Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO
  • Collaborators and Core Labs:
    John T. Belisle, Ph.D., Colorado State University
    Herbert P. Schweizer, Ph.D., Colorado State University
    Animal Models Core, Colorado State University

RM RP 005: Burkholderia pseudomallei antimicrobial resistance mechanisms

Introduction: Overcoming Gram-negative antibiotic resistance will be the major challenge for drug discovery efforts over the next decade; but how can we control antibiotic resistance when we don’t understand it? What we learn about antimicrobial resistance with Bp will be directly applicable to similar problems faced with other non-enteric Gram negative pathogens.

  • Principal Investigator: Herbert P. Schweizer, Ph.D.
  • Institution: Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO
  • Collaborators and Core Labs: Genomics Proteomics Core, Colorado State University

RM RP 006: Development of Novel Broad Spectrum Chemotherapeutics Against Priority Pathogens

Introduction: This project is to develop novel and highly effective broad spectrum chemotherapeutics against F. tularensis, B. pseudomallei and Y. pestis infections. In addition, such novel broad spectrum inhibitors can be used against other hard to treat bacterial agents with significant health relevance, particularly Gram-positive pathogens, including MRSA and Gram-negative pathogens including B. cenocepacia, Acinetobacterbaumannii, and Pseudomonas aeruginosa.

  • Principal Investigator: Richard A. Slayden, Ph.D.
  • Institution: Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO
  • Co-Principal Investigator: Peter J. Tonge, Ph.D.
  • Institution: Stony Brook University, Department of Chemistry, Stony Brook, NY
  • Collaborators and Core Labs:
    Herbert P. Schweizer, Ph.D., Colorado State University
    Animal Models Core, Colorado State University
    Genomics Proteomics Core, Colorado State University

RM RP 008: Inhibitors of the Twin Arginine Translocase system in Burkholderia pseudomallei

Introduction: The development of new agents for the treatment of infections has significantly trailed behind the rapid expansion of resistant pathogens. This is also exacerbated by the failure to identify novel antimicrobial targets during the past two decades. Accordingly, we have identified a worthy target in the Select Agent Burkholderia pseudomallei, and we are identifying and characterizing specific inhibitors directed at this target to ultimately use as antimicrobial agents in the treatment B. pseudomallei infections (e.g. melioidosis).

  • Principal Investigator: Michael L. Vasil, Ph.D.
  • Institution: University of Colorado Denver, Department of Microbiology, Aurora, CO
  • Collaborators and Core Labs:
    Herbert P. Schweizer, Ph.D., Colorado State University
    Product Development and Manufacturing Core, Colorado State University
    Genomics, Proteomics Core, Colorado State University

RM RP 009: Mechanisms of Burkholderia pseudomallei drug tolerance

Introduction: Melioidosis caused by Burkholderia bacteria kills a high percentage of infected people, making this microbe a highly coveted agent for bioterrorism. Treatment is hampered by natural and host-induced resistance of Burkholderia to antibiotics. It is imperative we find new antibacterials that eliminate the infection from infected individuals. Our investigations will identify and test drugs capable of curing infections with Burkholderia.

  • Principal Investigator: Andres Vazquez-Torres, DVM, Ph.D.
  • Institution: University of Colorado Denver, Department of Microbiology, Aurora, CO
  • Co-Principal Investigator: Martin I. Voskuil, Ph.D.
  • Institution: University of Colorado Denver, Department of Microbiology, Aurora, CO
  • Collaborators and Core Labs:
    Steven W. Dow, Ph.D., Colorado State University
    Animal Models Core, Colorado State University

Viral Therapeutics

RM RP 003: Development of a novel antiviral therapy targeting multiple alphaviruses

Introduction: Eastern and western equine encephalitis viruses (EEEV and WEEV) are listed as category B agents (NIAID) and EEEV as a select agent by HHS and USDA. These viruses have potential for causing severe emerging disease outbreaks and for development as bioweapons. Old World alphaviruses such as chikungunya are emerging into new regions. There are no human antiviral therapies for alphaviruses in case of a widespread outbreak of disease. There is a need to develop novel platforms and adjuvant technologies that will allow us to target multiple alphaviruses.

  • Principal Investigator: Kenneth E. Olson, Ph.D.
  • Institution: Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO
  • Co-Principal Investigator: Donald L. Jarvis, Ph.D.
  • Institution: University of Wyoming, Department of Molecular Biology, Laramie, WY
  • Co-Principal Investigator: Ann Powers, Ph.D.
  • Institution: Centers for Disease Control and Prevention, ADB, DVBID, Fort Collins, CO
  • Collaborators and Core Labs: Animal Models Core, Colorado State University

RM RP 010: Treatment of acute West Nile virus disease and neurological sequelae

Introduction: Many patients first visit physicians after West Nile virus has infected the brain or spinal cord. Antiviral or neuroprotective treatments, developed in this proposal, that are effective when administered during acute viral infection of neurons or during subsequent neurological sequelae will be important for solving this public health problem.

  • Principal Investigator: John D. Morrey, Ph.D.
  • Institution: Utah State University, Department of Animal, Dairy and Veterinary Sciences, Logan, UT
  • Collaborators and Core Labs:
    Yousuke Furuta, Ph.D., Toyama Chemical Company
    Syd Johnson, Ph.D., Macrogenics IncoRMRPorated
    Venkatraman Siddharthan, Ph.D., Utah State University
    Brian Gowen, Ph.D., Utah State University
    Jeffrey Hall, DVM, Ph.D., Utah State University

RM RP 011: T-705 pyrazine derivative treatment of highly pathogenic arenaviral infections

Introduction: This project focuses on the development of a new antiviral therapy based on T-705 for the often fatal diseases caused by the South American hemorrhagic fever arenaviruses. This research will also compliment the development of T-705 for the treatment of Lassa fever, caused by the Old World Lassa arenavirus.

  • Principal Investigator: Brian B. Gowen, Ph.D.
  • Institution: Utah State University, Department of Animal, Dairy and Veterinary Sciences, Logan, UT
  • Co-Principal Investigator: Jack H. Nunberg, Ph.D.
  • Institution: Montana Biotechnology Center, University of Montana, Missoula, MT
  • Collaborators and Core Labs:
    Yousuke Furuta, Ph.D., Toyama Chemical Company
    Jeffrey Hall, DVM, Ph.D., Utah State University
    Michael Holbrook, Ph.D., University of Texas Medical Branch
    Donald Smee, Ph.D., Utah State University

RM RP 013: Human monoclonal antibodies (huMAbs) for medically important arboviruses

Introduction: There are few vaccines and no antiviral therapeutics available for use in human infections with the emerging, medically important arboviruses Venezuelan equine encephalitis (VEEV), yellow fever (YFV) or dengue (DENV) viruses. This project will develop safe and effective human antibodies that can be used in preventing or curing human VEEV, YFV or DENV infections.

  • Principal Investigator: Carol D. Blair, Ph.D.
  • Institution: Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO
  • Co-Principal Investigator: John T. Roehrig Ph.D.
  • Institution: Centers for Disease Control and Prevention, VBIDL, Fort Collins, CO
  • Collaborators and Core Labs:
    Larisa Poluektova, MD, Ph.D., University of Nebraska Medical Center
    Animal Models Core, Colorado State University
    Product Development and Manufacturing Core, Colorado State University

RM RP 014: A Novel Antiviral Approach Using the Cellular RNA Decay Machinery

Introduction: We have recently made the novel discovery that several viruses actively suppress the host cell RNA decay machinery to promote virus infection. We propose to test whether other viruses suppress this cellular defense machinery by a similar mechanism and develop novel antiviral drugs that reverse this suppression. These drugs could then be used to treat infections with multiple viruses of biodefense significance.

  • Principal Investigator: Jeffrey Wilusz, Ph.D.
  • Institution: Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO
  • Co-Principal Investigator: Joseph F. Krebs, Ph.D.
  • Institution: BIOO Scientific, Austin, Texas
  • Collaborators and Core Labs:
    Lance Ford, Ph.D., BIOO Scientific, Austin, Texas
    Genomics Proteomics Core, Colorado State University

RM RP 016: Development and Optimization of Novel Anti-Flavivirus Compounds

Introduction: Mosquito-borne hemorrhagic-fever resulting from flavivirus infection causes significant human morbidity and mortality throughout the world, yet there are currently no effective therapeutics to treat infected patients. The goal of this project is to utilize biochemical and rational drug design methodologies to identify and characterize broadly active antiviral compounds targeting the conserved flaviviral methyltransferase.

  • Principal Investigator: Brian J. Geiss, Ph.D.
  • Institution: Colorado State University, Department of Microbiology, Immunology and Pathology, Fort Collins, CO
  • Co-Principal Investigator: Susan M. Keenan, Ph.D.
  • Institution: University of Northern Colorado, School of Biological Sciences, Greeley, CO
  • Collaborators and Core Labs: Animal Models Core, Colorado State University

RM RP 018: Vascular Stabilization as a Broad Therapeutic Platform for Biodefense

Introduction: At present, there is an emphasis on developing different drugs for different pathogens. We will explore a strategy based on blunting the vascular response to cytokines that may provide a common platform for treating multiple pathogens.

  • Principal Investigator: Dean Li, MD, Ph.D.
  • Institution: University of Utah, Department of Molecular Medicine, Salt Lake City, UT
  • Collaborators and Core Labs: Animal Models Core, Colorado State University

RM RP 019: Arenavirus entry and its inhibition

Introduction: Arenaviruses are responsible for hemorrhagic fevers with high mortality. Effective therapies against Lassa fever, Argentine hemorrhagic fever and others are urgently needed to address ongoing public health and Category A biodefense concerns. The goal of this project is to develop potent and broadly active small-molecule inhibitors that prevent arenavirus envelope glycoprotein-mediated entry into the host cell. These compounds will be useful for the treatment of arenavirus infection and disease.

  • Principal Investigator: Jack H. Nunberg, Ph.D.
  • Institution: Montana Biotechnology Center, University of Montana, Missoula, MT
  • Co-Principal Investigator: John Gerdes, Ph.D.
  • Institution: University of Montana, Department of Biomedical/Pharmaceutical Sciences, Missoula, MT
  • Collaborators and Core Labs:
    Dennis Hruby, Ph.D., SIGA Technologies
    Sean Amberg, Ph.D., SIGA Technologies