Islet Biology / Immunology
Descriptor of Research
My laboratory investigates the molecular details of Mycobacterium tuberculosis pathogenesis. Diabetes mellitus (DM) is the most problematic comorbidity for tuberculosis (TB) patients, where DM patients are at three-times the risk of developing active TB as non-DM patients infected with M. tuberculosis and at double the risk of death and poor TB-treatment outcomes5. Globally, an estimated 15% of patients with active TB have DM6. To better protect DM patients from TB, we need to understand how alterations in their immune function favors developing active TB disease. Recently, a systems biology comparison of T2DM patients, TB patients, comorbid patients, and healthy individuals was performed to search for a causative link in DM/TB comorbidity. Bayesian Network modeling of a large panel of clinical parameters found neutrophilic inflammation as a central feature of DM/TB corresponding with a high degree of transcriptomic alterations in comorbid patients. Dysfunctional neutrophils have been implicated in DM vascular complications (i.e. retinopathy, nephropathy) and impaired wound healing, but it is unclear how they contribute to disease outcomes in M. tuberculosis-infected DM patients. My laboratory has recently demonstrated that neutrophils directly impact the outcomes of M. tuberculosis infections, and we are currently applying our studies to understand how neutrophil function is altered during DM and how this impacts immune responses to M. tuberculosis.