Research Expertise and Interest

TB, Mycobacterium tuberculosis, M. tuberculosis, genetics, proteomics, transcriptional profiling, host-pathogen interactions, host-directed therapy

Research Description

Tuberculosis has been a major global health concern for well over a century. Although many potential treatments have been vigorously pursued, conventional strategies have failed to eradicate TB infection and, in fact, the global threat has grown over the last couple decades. Professor Cox believes that failure results in part from the fact that such attempts have neglected to take into account the deeply integrated, symbiotic-like relationship between Mycobacterium tuberculosis and its host that has developed over 40,000 years of human/bacterial co-evolution. His research group aims to understand the key mechanisms that dictate the M. tuberculosis-human relationship with the goal of breaking these ties, targeting either host or pathogen factors to eliminate M. tuberculosis infection and, with that, to contribute to solving a steadily increasing threat in global health. In particular, while current vaccine strategies aimed at promoting specific immune responses (e.g. T-cells and cytokines) to various M. tuberculosis antigens have failed, they believe that promoting innate responses of host cell macrophages, the cell type where M. tuberculosis grows, represents an unconventional strategy to block bacterial infection.

Their perspective on M. tuberculosis infection has been shaped primarily from their results showing that macrophages have unexpected potential to intrinsically control bacterial viability and to shape specific immune responses. Conventional wisdom in the innate immunity field is that detection of pathogens is accomplished by cellular receptors that recognize unique molecular structures of microbes, giving rise to stereotypical transcriptional responses that promote inflammation. While certainly true, the work of his lab and that of others supports a more sophisticated view in which macrophages integrate information about the nature of engulfed pathogens in order to fashion unique responses. Using quantitative cell-mapping technologies including CRISPR genetics and mass spectrometry-based proteomics, his lab has found that macrophages can discriminate virulent from non-virulent M. tuberculosis at the earliest stages of infection. These changes play fundamental roles in shaping the innate responses to infection and can work to restrict bacterial growth in dramatic fashion. This avenue of research represents a vast area for new biological discovery and they seek to understand the function and mechanism of the pathways elicited, to identify pathogen strategies for averting these effects, and to harness this powerful anti-infection system for therapeutic purposes.