The HTRL is a platform for basic research on the molecular mechanisms of infectious diseases, and translational research applying basic findings to the development of products such as diagnostics, therapeutics and vaccines.
The current research projects at the HTRL include:
Plague is historically one of the deadliest human infectious diseases. It is endemic in the western US and is a frequent pathogen of prairie dogs. Plague is caused by Yersinia pestis, a gram – negative bacillus. It is transmitted by fleas and can infect humans. Currently there is a need for an effective vaccine. Researchers at the HTRL are developing a novel recombinant plague vaccine based on the LcrV protein, a component of the Y. pestis type III secretion system.
Anthrax is a deadly bacterial infection caused by Bacillus anthracis, a spore-forming, gram-positive bacillus. Anthrax spores are extremely resistant to heat, desiccation and other forms of disinfection. Spores can also be easily dispersed in the environment. HTRL researchers are taking several approaches to developing therapeutics that target assembly of the B. anthracis capsule and an effective anthrax vaccine based on an engineered form of a secreted anthrax toxin.
Methicillin resistant Staphylococcus aureus is now the most common infection that requires hospitalization in the US. This gram – positive coccus is easy to grow and manipulate genetically. Researchers at HTRL are developing novel therapeutics based on research that identified several new virulence determinants. In addition, a recombinant vaccine, developed at HTRL, based on Protein A, a major S. aureus virulence determinant is close to entering into clinical trials.
Rickettsia species cause Rocky Mountain spotted fever and typhus, both infectious diseases that are transmitted to people by ticks. R. conori is the agent of Mediterranean spotted fever. The genus Rickettsiae was named in honor of Howard T. Ricketts in honor of his contributions in establishing R. rickettsia as the agent of Rocky Mountain Spotted Fever. All Rickettsia species are obligate intracellular pathogens. HTRL researchers are developing specific Rickettsia surface proteins as vaccine candidates.
Brucellosis is both a disease of cattle and humans. It is caused by Brucella abortus, a gram – negative bacillus. Brucellae are highly communicable and resistant to environmental stresses such as heat, oxidation and acid. Researchers at HTRL are studying the molecular mechanisms of resistance to environmental stresses and its relationship to virulence to develop better therapeutics.
Coxiella burnetii causes Q (query) fever, an endemic disease of sheep, cows and people. Although Q fever is rarely fatal, C. burnetii was successfully weaponized and the minimum dose to produce disease in people is 1 organism. Coxiella is also environmentally robust and resistant to heat drying and acid, in fact it grows best at pH 4. HTRL researchers are using C. burnetii to search for human genes that are required to support infection by Coxiella and target those functions with drugs to make the human cells resistant to infection.
The highly pathogenic avian H5N1 influenza viruses, currently endemic in domestic poultry in three different continents, have been a looming threat for the past 15 years. They have the potential to cause a human influenza pandemic, as most of us do not carry antibodies against it. Researchers at the HTRL are developing vaccines that can offer protection against all circulating H5N1 strains.