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Heads of Laboratories

Head shot of Howard Hang
Howard C. Hang, Ph.D.
Richard E. Salomon Family Associate Professor
Laboratory of Chemical Biology and Microbial Pathogenesis
Howard.Hang@rockefeller.edu

Microbial pathogens have evolved sophisticated virulence mechanisms to subvert host defenses and cause disease. The Hang laboratory is interested in elucidating fundamental mechanisms of host-microbe interactions and developing new therapeutic strategies to combat microbial infections.

The emergence of new microbial pathogens and the adaptation of microbes to current antimicrobials demands a better understanding of host-microbe interactions to prevent and treat infections. To accomplish this, there is a need for new methods to analyze the roles of gene and protein families involved in these interactions. The Hang laboratory has developed robust chemical methods to image and profile nucleic acid and protein synthesis, as well as modifications to these molecules in animal cells and microbes. At the heart of this chemical approach is the design and synthesis of specific reporters, which are metabolites bearing uniquely reactive groups that can be incorporated into biomolecules and then selectively labeled. The Hang laboratory has developed a variety of chemical reporters for the sensitive detection and analysis of nucleic acid and protein synthesis, as well as a variety of chemical modifications.

The application of these new reporters to different organisms and cell types has revealed previously uncharacterized protein modifications and regulatory mechanisms involved in host-microbe interactions, as well as fundamental aspects of cell biology. For example, fatty acid and isoprenoid chemical reporters used in dendritic cells and macrophages have revealed lipidation of key immune effectors and receptors responsible for controlling microbial infections. In addition to host immunity, lipid chemical reporters from the Hang laboratory have revealed new roles for protein S-palmitoylation in cellular differentiation, as well as bacterial virulence. These studies suggest that protein lipidation mechanisms can regulate the strength and specificity of cell signaling pathways and highlight lipid modifications and metabolism as key regulatory factors in host-microbe interactions and as potential targets for pathogens during infection. These results are driving further mechanistic studies in the Hang laboratory.

With the dwindling supply of antibiotics and a growing appreciation for commensal microbes, new anti-infective strategies are needed to selectively target microbial pathogens without depleting the beneficial microbiota in humans. The Hang laboratory is interested in understanding protective mechanisms of commensal bacteria and developing inhibitors of bacterial virulence pathways. While host-associated bacterial species have been shown to secrete metabolites and proteins with beneficial effects for the host, the mechanisms and targets of these molecules are not well understood. The Hang laboratory is therefore employing chemical reporters and model organisms to identify and characterize key protective factors from commensal bacteria. As a complement, the Hang laboratory is also developing chemical inhibitors of key microbial virulence pathways to limit infections. Specifically, the lab is working on small molecule inhibitors of type III secretion systems (T3SSs) essential to virulence in many Gram-negative pathogens. The Hang laboratory has developed a high throughput assay for type III protein secretion and so discovered specific small molecules from medicinal plants and synthetic chemical libraries that can antagonize T3SSs and inhibit bacterial infection. These T3SS inhibitors provide new lead compounds for selectively targeting bacterial pathogens responsible for disease without killing protective commensal bacteria.


EDUCATION

B.S. in chemistry, 1998
University of California, Santa Cruz

Ph.D. in chemistry, 2003
University of California, Berkeley

POSTDOC

Harvard Medical School and Whitehead Institute for Biomedical Research, 2004–2006

POSITIONS

Assistant Professor, 2007–2013
Associate Professor, 2013–
The Rockefeller University

AWARDS

Irma T. Hirschl/Monique Weill-Caulier Trust Research Award, 2007

Ellison Medical Foundation New Scholar Award, 2008

SELECTED PUBLICATIONS

Grammel, M. and Hang, H.C. Chemical reporters for biological discovery. Nat. Chem. Biol. 9, 475–484 (2013).

Zhang, M.M. et al. Quantitative control of protein S-palmitoylation regulates meiotic entry in fission yeast. PLoS Biol. 11, e1001597 (2013).

Charron, G. et al. Prenylome profiling reveals S-farnesylation is crucial for membrane targeting and antiviral activity of ZAP long-isoform. Proc. Natl. Acad. Sci. U.S.A. 110, 11085–11090 (2013).

Yount, J.S. et al. Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3. Nat. Chem. Biol. 6, 610–614 (2010).

Yount, J.S. et al. Visible fluorescence detection of type III protein secretion from bacterial pathogens. J. Am. Chem. Soc. 132, 8244–8245 (2010).


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.