Current Research and Scholarly Interests
Granulomas are organized aggregates of immune cells which form in response to particulate matter that the body cannot readily clear. Granulomas evolved as protective responses to destroy or sequester harmful particles but become pathological in numerous medically important infectious and non-infectious inflammatory diseases, such as tuberculosis (TB), schistosomiasis, sarcoidosis, Crohn’s disease, and foreign body reactions which constitute serious complications of medical implants, necessitating their removal.
In tuberculosis (TB), the granuloma exerts both host-beneficial and -detrimental functions which shape disease severity and outcomes. Mycobacterium tuberculosis, the causative agent of human TB, has evolved mechanisms to manipulate the granulomatous response for its advantage. My lab seeks to understand how host-mycobacterium interactions shape TB pathogenesis. We study the virulence mechanisms that mycobacteria utilize to adapt to or manipulate the granuloma as well as the immune mechanisms that mediate host defense versus immunopathology.
Zebrafish infected with Mycobacterium marinum, a natural fish pathogen closely related to M. tuberculosis, develop TB-like disease characterized by the formation of necrotic granulomas like those found in humans with severe TB. We have identified another small freshwater fish species that is naturally resistant to M. marinum and forms granulomas that seldom become necrotic. We exploit the unique genetic and imaging capabilities of these complementary fish models and integrate this work with studies of human TB. We believe that by investigating the cues governing TB granuloma form and function, our studies will specifically illuminate TB pathogenesis, uncover new concepts in immunobiology, and may produce medically relevant insights for a wide range of inflammatory diseases.