Professor; Vice Chair, Faculty Development
Infectious Diseases; Oncology
I care for hospitalized patients and outpatients at Roswell Park Cancer Institute (RPCI), where I am head of Infectious Diseases. My area of clinical expertise relates to infections in patients with cancer and stem cell transplant recipients, and I have served on several national panels that establish guidelines for preventing, diagnosing, and managing infections in these patients. I also have a specific interest in patients with primary phagocytic disorders (e.g., chronic granulomatous disease).
RPCI is the site of my clinical teaching. I also teach medical students in lecture settings and in small group sessions in their first and second years, including courses in lung pathophysiology and microbiology-immunology. We intermittently have students in our lab and participate in a grant designed to encourage medical students to become physician-scientists.
I mentor residents in their clinical training and in research. I also teach fellows in all aspects of their training and mentor those who perform their research projects in my lab.
I have an active, nationally funded translational research program. The major focus of our lab is studying NADPH oxidase as a critical regulator of inflammation and host defense. NADPH oxidase is an emergency host defense pathway that is rapidly activated in response to certain microbial products, and converts molecular oxygen to superoxide anion and downstream reactive oxidant intermediates (ROIs). Chronic granulomatous disease is an inherited disorder of the NADPH oxidase characterized by severe bacterial and fungal infections (e.g., invasive aspergillosis) and by excessive inflammation. In addition to its critical host defense role, our lab, in collaboration with colleagues, found that NADPH oxidase also functions to restrain inflammation by modulating redox-sensitive innate immune pathways. NADPH oxidase also affects T-cell responses, including the balance between Tn17 and regulatory T-cells. We have an NIH grant to further elucidate mechanisms by which NADPH oxidase regulates inflammation.
We believe that our work has broad relevance to human diseases associated with inflammation, such as inflammation-induced injury and tumor immunology. Indeed, several of the pathways that NADPH oxidase regulates are important in tumorigenesis and the tumor microenvironment (e.g., NF-kB, Nrf2, IL-17, Tregs), and are potential therapeutic targets. In collaboration with colleagues, we are examining how NADPH oxidase influences tumor immunity.