Tuberculosis Research Unit at University of Washington

Primary Investigator: Thomas Hawn, Jeffery Cox (University of California, Berkeley)

Hurdles for controlling tuberculosis (TB) include developing a highly efficacious vaccine, preventing transmission and infection in endemic areas, and discovering drug treatment regimens that work rapidly and kill dormant bacilli within macrophages. After exposure to Mtb, outcomes vary widely including resistance, asymptomatic latent infection, active pulmonary disease, and disseminated infections including TB meningitis (TBM). This heterogeneity complicates clinical treatment decisions with regards to choosing the number of drugs and duration of treatment. This broad clinical spectrum may also provide an understanding of the biological mechanisms that control TB pathogenesis. A major source of heterogeneity is a combination of genetic variation in both humans and Mtb that are evolving under constant selective pressure. The objective of this team of researchers is to use genetic, genomic, proteomic, and bioinformatic strategies to discover host and pathogen variants of genes and gene products that are associated with TB clinical outcomes and to determine how these variants interact to regulate molecular, cellular, and in vivo functions. Researchers will study two cohorts in Vietnam and Uganda that capture the full spectrum of resistance to traditional latent TB infection (LTBI), LTBI, pulmonary TB disease, and disseminated disease in the form of TBM. The multidisciplinary program will examine an overall hypothesis that variants of Mtb and host genes dictate heterogeneous clinical outcomes and encode factors that interact with and alter innate immune cells.

For more information about the TBRU’s projects, please see the following summaries in RePORTER:

Host pathogen variation & TB pathogenesis (U19AI162583)

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