Heads of Laboratories
Howard C. Hang, Ph.D.
Richard E. Salomon Family Associate Professor
Laboratory of Chemical Biology and Microbial Pathogenesis
Microbial pathogens have evolved sophisticated virulence mechanisms to subvert host defenses and cause disease. Dr. Hang is interested in developing chemical tools to understand how microbes evade host immune responses and identifying chemical inhibitors targeted at virulence pathways to combat microbial infections.
Microbial pathogens have evolved sophisticated virulence mechanisms to subvert host defenses and cause disease. Dr. Hang’s laboratory is interested in understanding how microbes evade host immune responses and in developing chemical inhibitors targeted at virulence pathways to combat microbial infections.
As host membranes provide a key physical barrier for infection, bacterial pathogens and viruses often utilize complex mechanisms to remodel cellular membranes to enter host cells and cause disease. Understanding host-pathogen interactions at the membrane interface may therefore provide new opportunities to prevent infections. To dissect the mechanisms by which microbial pathogens manipulate host membranes, the Hang laboratory has developed specific lipid chemical reporters and bioorthogonal labeling methods to robustly visualize and identify novel lipid-modified and membrane-associated proteins that are crucial for host resistance to infection. In particular, chemical proteomics and functional studies from the Hang laboratory have revealed that protein lipidation mechanisms (S-palmitoylation and S-prenylation) can control the membrane targeting and activity of several proteins involved in host immunity, including interferon-stimulated effectors such as IFITM3 and innate immunity receptors. These studies suggest that protein lipidation mechanisms can regulate the strength and specificity of host immune responses and highlight lipid modifications and metabolism as potential cellular pathways for pathogen interference during infection. To further understand the mechanistic and functional roles of these lipid-modified immune effectors and receptors in host immunity and infection, the Hang laboratory is currently performing in vitro reconstitution studies of these immune proteins and evaluating their activity in cellular and animal models of infection. In addition to lipid chemical reporters, the Hang laboratory has also developed chemical reporters for other protein modifications (acetylation, AMPylation and ADP-ribosylation) to explore their functional roles in host defense and microbial pathogenesis.
To limit infections from microbial pathogens, the Hang laboratory is interested in developing chemical inhibitors of key microbial virulence pathways and characterizing their mechanisms of action. Notably, the injection of bacterial protein effectors into host cells through type III secretion systems is essential for the virulence of many gram-negative bacterial pathogens, which make these secretion systems prime targets for the development of anti-virulence inhibitors. To identify potent small-molecule inhibitors of this crucial bacterial virulence pathway, the Hang laboratory has developed a high throughput assay for type III protein secretion and discovered specific small molecules from medicinal plants and synthetic libraries that can antagonize them and inhibit bacterial infection. These inhibitors are not broadly bactericidal and provide new lead compounds for selectively targeting bacterial pathogens responsible for disease without perturbing the beneficial host microbiota.
Dr. Hang received his undergraduate degree in chemistry from the University of California, Santa Cruz, in 1998 and his Ph.D. in chemistry from the University of California, Berkeley, in 2003. He was a Damon Runyon Cancer Research Foundation postdoctoral fellow at Harvard Medical School and the Whitehead Institute for Biomedical Research. He joined Rockefeller in 2007 as assistant professor and head of laboratory and was appointed associate professor in 2013.
Dr. Hang has received the Irma T. Hirschl/Monique Weill-Caulier Trusts Research Award in 2007 and an Ellison Medical Foundation New Scholar Award in Aging in 2008.
Dr. Hang is a faculty member in the David Rockefeller Graduate Program, the Tri-Institutional M.D.-Ph.D. Program and the Tri-Institutional Ph.D. Program in Chemical Biology.
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