Using Global Proteomics to Discover New Anti-TB Pathways of Macrophages

Event Details

Type

Friday Lecture Series

Speaker(s)

Jeffery Cox, Ph.D., C.H. Li Endowed Chair of Biochemistry and Endocrinology; Faculty Director, Center for Emerging and Neglected Diseases; professor of molecular and cell biology, University of California, San Francisco

Speaker bio(s)

Macrophages are critical for controlling many bacterial infections but many pathogens, including Mycobacterium tuberculosis, can hijack these cells and use them as sites of replication. The pathways that control intracellular bacterial growth and how they are manipulated by pathogens are not completely understood. We have utilized cutting-edge mass spectrometry techniques to comprehensively probe the interactions between macrophages and three intracellular bacterial pathogens, M. tuberculosis, Salmonella, and Listeria. Monitoring both host-microbe protein-protein interactions and host post-translational modification has uncovered new targets and pathways that influence antibacterial responses and bacterial growth. Our results revealed thousands of ubiquitylation and phosphorylation events that occur early after infection, most of which were previously unknown. Unlike transcriptional responses to bacterial infection, which are largely monotonic, our results reveal a surprising diversity in ubiquitin-mediated responses specific to each pathogen. Likewise, using well-defined attenuated bacterial mutants revealed a remarkable ability of macrophages to discriminate virulent from non-virulent bacteria, suggesting macrophages can integrate information about the nature of the engulfed bacteria and elicit unique responses. These studies have uncovered a unique mechanism by which bacterial pathogens suppress antibacterial immune responses by activating inappropriate antiviral innate responses.

Jeffery Cox received a BS in Biochemistry from UC Berkeley and studied immunology in the laboratory of Dr. Marian Koshland. He pursued his graduate studies at UC San Francisco in the laboratory of Dr. Peter Walter, where he made the initial discoveries of the unfolded protein response in yeast and received a Ph.D. in Biochemistry and Biophysics. Jeff moved across the country for a postdoctoral fellowship with Dr. Bill Jacobs at Albert Einstein School of Medicine, where he developed new genetic strategies that allowed him to identify key virulence factors in M. tuberculosis. He subsequently returned to UC San Francisco as an Assistant Professor in the Department of Microbiology & Immunology and established his research program studying the mechanisms of M. tuberculosis pathogenesis during his 15-year career there. In January 2016, Jeff returned to UC Berkeley as Professor of Molecular and Cell Biology and as Faculty Director of the Center for Emerging and Neglected Diseases (CEND).

Open to

Public

Host

Luciano Marraffini

Reception

Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge

Contact

Justin Sloboda

Phone

(212) 327-7785

Sponsor

Justin Sloboda
(212) 327-7785
jsloboda@rockefeller.edu