I completed a joint MD/PhD degree program, focusing my clinical electives on infectious disease and immunology. Although I did not pursue a residency, my MD training has instructed the trajectory of my research program. I have a broad whole-body foundation of anatomy and physiology that allows me to be facile in moving into new research areas. For example: 1) a knowledge of clinical sepsis facilitated our studies of in vivo LPS shock; 2) a prior exposure to chronic granulomatous disease (CGD) inspired our move to study CGD pathogens; and 3) understanding liver histologic anatomy facilitated our study of liver infection. 

During my PhD research I discovered and characterized type III secretion (T3SS) effectors in Salmonella, giving me an understanding of microbial virulence factors and intracellular pathogens. In my post-doctoral research I discovered that the NLRC4 inflammasome detects T3SS activity by sensing flagellin or T3SS rod protein translocation, and published the first demonstration that pyroptosis was a bona fide in vivo defense mechanism to clear intracellular bacteria. In my independent lab at UNC, we discovered that caspase-11 is the cytosolic sensor for LPS, and the resulting pyroptosis defends against cytosol-invasive bacterial infection.

My lab, now at Duke, broadly studies regulated cell death as a defense against infection. We study a broad array of pathogens. We discovered ubiquitous environmental pathogens that are eliminated by pyroptosis so efficiently that they never cause symptomatic infection in immunocompetent hosts (Burkholderia thailandensis and Chromobacterium violaceum). In contrast, bona fide pathogens (e.g. Salmonella and Listeria) typically evolved to evade pyroptotic defenses, enabling them to cause disease in immunocompetent people. By comparing bona fide pathogens to environmental pathogens, we are elucidating the evolutionary importance of regulated cell death as an immunologic defense.

Most recently, we broadened our scope to include how other forms of cell death act in defense against infection. This led us to discover the unique function of caspase-7 that acts as a cell death facilitator during both apoptotic and pyroptotic cell death. We discovered that caspase-7 cleaves and activates acid sphingomyelinase in order to counteract perforin pores after NK and CTL attack, and to counteract gasdermin D pores after caspase-1 activation in intestinal epithelial cells.