The interface between inorganic chemistry and immunology represents a rich and open area for investigation, as infectious pathogens and human hosts alike share a common need for metals like copper, iron, and zinc for their survival, growth, and development. Because these essential nutrients cannot be synthesized but must be acquired and stored, unraveling the molecular details of this metal tug-of-war between invading microbial pathogens and potential hosts represents a significant scientific challenge. We are interested in understanding, at the molecular level, how dynamic changes in metal homeostasis pathways of the host and pathogen influence the innate immune response, pathogenicity, and/or virulence. Molecular imaging provides an attractive approach for studying such host-pathogen interactions in real time.

Global Metal Homeostasis in Host-Pathogen Systems. During cycles of infection and pathogenicity/virulence, the host and invading pathogen compete for available metal nutrients in their local environments. We are developing new ways to image or manipulate the inorganic chemistry used by the innate immune response to counteract the tactics of the invading pathogen as it seeks adhere, survive, and/or spread. In particular, we are interested in the contribution of labile, exchangeable forms of the essential transition metals copper, iron, and zinc to these interactions. Fluorescent, luminescent, and MRI probes for metal imaging, as well as new chelators and caged compounds for metal pool manipulation, are being developed to study microbial and immune cells together or in isolation.