John is working to establish an independently-funded research program at the Trudeau Institute that focuses on the adaptive response of mycobacteria to host immunity.
Nontuberculous Lung Disease (NTM) and Tuberculosis (TB) are lung diseases caused by the bacteria Mycobacterium avium and M. tuberculosis. The interplay between pathogenic bacteria and their host is characterized by a complex, dynamic escalation of responses in which both bacterium and host co-adapt. This co-adaptation results in chronic lung disease whose hallmark is an inflammatory or granulomatous lesion. These lesions serve to contain the infection, to isolate surrounding tissue from immune-mediated damage and to create a biochemically hostile environment that restricts the growth of the bacilli.
The goal of John’s research program is to identify the traits responsible for the capacity of M. avium and M. tuberculosis to survive and grow in the hostile environment found within these lesions. His research program approaches this problem from the perspective that the bacilli sense their environment using a variety of extra- and intracellular mechanisms and integrate these sensory inputs to induce specific patterns of gene expression. These changes in gene expression result in metabolic remodeling in order to modify, escape or evade the host response. We propose that bacterial adaptation to the host immune response is critical to its long-term persistence and intractability to chemotherapy.
By defining the adaptive response of mycobacteria to host immune stress John hopes to be able to drive the bacilli into a physiological phenotype that alters susceptibility to currently ineffective chemotherapeutic treatments. John's research will define the contribution of mycobacterial physiology to the chronic disease process. Most importantly, John’s research has the potential to identify new drug targets and result in improved patient outcomes.