Rocky Mountain Regional Center of Excellence

Current Research Projects

• Role of Innate Immunity in Pulmonary Burkholderia Infection
  Burkholderia mallei and others in the genus have significant potential for use as bioweapons, yet little is known about the pathogenesis of pneumonic Burkholderia infection. For example, the key effector cells or cytokines regulating innate »»
  
• Isoprenoid Biosynthesis: a target for drugs against category A-C pathogens
  The NIAID biodefense research agendas for category A-C agents have identified a need for a broader, more robust arsenal of anti-infective agents. This is important when considered in the light of recent research in genomics and immunology, which has greatly eased the task of genetic manipulation of pathogens.»»
  
• Immunoproteome of F. tularensis
  Francisella tularensis is a gram-negative facultative intracellular pathogen that causes lethal disease in humans, and is a potential biowarfare agent. Surprisingly little is known about the overall protein physiology of this bacterium, and only a handful of potential vaccine candidates are identified at the molecular level.»»
  
• Burkholderia spp: Novel Therapeutic Approaches
  Burkholderia pseudomallei (BP) is a prime candidate for use in biowarfare and bioterrorism because it can be easily obtained (from the environment in endemic areas), propagated and prepared (robust organism rapidly growing on simple media), easily dispersed with high infectivity (aerosolization and contamination of water), and causes a rapidly developing, severe disease (melioidosis) with high mortality, even when properly diagnosed. »»
  
• Fur-regulated genes and siderophore-dependent iron uptake in Burkholderia
  The role of iron in gene regulation and its acquisition is crucial to bacterial pathogenesis. Nevertheless, the mechanisms governing iron regulation and acquisition in the Class B Select Agents Burkholderia pseudomallei and mallei are not well understood.»»
  
• Oxidative and Nitrosative stress in Burkholderia
  During the course of infection, intracellular pathogens adapt to host-mediated stress conditions, including, the antibacterial actions of phagocytic cells. Mechanisms by which pathogens avoid these antibacterial agents are central to their survival. »»
  
• O2-dependent host defense in resistance to Burkholderia
  A variety of pathogenic microorganisms, including the Class B select agent Burkholderia, have devised strategies to withstand the challenges of the intracellular environment of professional phagocytes. Recent information has reveled that Burkholderia expresses a type III secretion system encoded in the bsa gene cluster that is essential to the intracellular survival of this pathogenic bacteria. »»
  
• Biochip Diagnostic Tool for BT Induced Diseases
  Precision Photonics Corporation proposes to develop a Biochip diagnostic system that can simultaneously test for a broad range of markers for human infectious diseases. The system consists of a multi-pathogen sensor that can rapidly detect up to 20 targets at once to diagnose infectious diseases of those presenting with symptoms consistent with a bioterror attack.»»
  
• Alphaviral Determinants of Infection in Mice
  Eastern, Venezuelan, and Western equine encephalitis (EEE, VEE, WEE) viruses (Alphavirus; Togaviridae) are mosquito-borne viruses causing severe encephalitis in humans and horses. All three viruses are listed as category B agents by both NIAID and CDC and as potential bioterrorism/biowarfare (BT/BW) agents. »»
  
• Biology of Vector and Aerosol Transmission of Bunyaviridae
  Arthropod-borne and Rodent-borne viruses in the family Bunyaviridaes represent a serious threat to both human and animal health. Most recently emerged viruses are from this family and many Bunyaviridae have significant potential as bioterrorism (BT) agents. »»
  
• Human Monoclonal Antibodies (Mabs) for VEE virus
  Using proprietary methodologies, Alexion Antibody Technologies (AAT), has produced phage display libraries expressing human antibody fragments (Fab) directed against Venezuelan equine encephalomyelitis virus (VEEV) from immunized military personnel. »»
  
• Treatment and Disease Markers for Alpha and Flaviviruses
  Our strategy has been to identify therapies, hopefully FDA-approved drugs or investigational new drugs ( IND). that might be used in off-label applications to treat viral encephalitis after the virus has infected the brain. »»
  
• Human Genes Shaping the Response to Bioterrorism Agents
  Emerging pathogens have a unique potential to be weaponized as bioterrorism agents because most humans have no immunity to such infections. The human response to these pathogens varies from aborted infection to overwhelming disease and death.»»
  
• Development of SERS Assays for West Nile Virus
  The purpose of this Rocky Mountain RCE research project is the development of rapid assays for the presence of West Nile Virus (WNV) and St. Louis Encephalitis (SLE). These two viruses are clinically similar at early stages and may be mistaken for one another by many diagnostic tests.»»
  
• Gene expression and manipulation in Coxiella burnetii
  Coxiella burnetii is the etiologic agent of Q fever, a potential bioweapon and select agent, and one of the most infectious pathogens known. However, there are few reports concerning this obligate intracellular agent's molecular pathogenesis or developmental cycle, and lack of a system for site-directed genetic manipulation has severely hampered research progress. »»
  
• Enhancement of innate immunity to Coxiella pneumonia
  The urgency in identifying countermeasures against biologic threats cannot be overstated. Biological weapons are real threats today and new vaccines and other countermeasures were needed “yesterday” to help protect the public and soldiers in high-risk areas, such as Iraq. Vaccines offer the “best” countermeasure, but few exist for many of the well-known threats.»»
  
• Immunopathogenesis of Coxiella pneumonia
  Because Coxiella burnetii is such a difficult organism to work with, there is little known about the immunopathogenesis of Q fever pneumonia. From the little work that has been done in this area and from what is known about immune responses to other intracellular bacteria, we hypothesize that a T1-like T cell response, with the production of IFN-γ, clears established Coxiella infection from the lung and, in addition, that a local immunoglobulin response in the lung can help the host to resist the initiation of infection after aerosol exposure to the pathogen.»»
  
• DNA Vaccine for Q fever
  Q fever is an understudied infectious disease caused by Coxiella burnetti. Q-Vax, formalin-inactivated whole bacteria, is currently the only human vaccine approved for Q fever. Attempts have been made to determine the protective epitopes, but such studies have not advanced into an efficacious subunit vaccine. »»