BBS Faculty Member - Marcia Goldberg

Marcia Goldberg

Department of Microbiology and Immunobiology

University Park
Bacterial Pathogenesis Laboratories
65 Landsdowne Street, Room 423
Cambridge, MA 02139
Tel: 617-768-8740; Lab: 617-768-8741
Fax: 617-768-8738
Email: marcia.goldberg@mgh.harvard.edu
Lab Members: 4 postdoctoral fellows, 1 undergraduate
Visit my lab page here.



Our lab focuses on the molecular nature of interactions between microbial pathogens and the host. Pathogenic bacteria have evolved complex mechanisms to subvert host cell signaling pathways to enhance disease processes. Our work focuses on uncovering the molecular signaling events that occur during bacterial infection of host cells. The bacterial pathogen Shigella, a major cause of illness and mortality among children worldwide, infects cells of the intestinal epithelium and uses cellular actin cytoskeletal and other pathways to disseminate through host tissue. We are investigating the molecular mechanisms by which secreted bacterial proteins modulate host proteins to divert the host signaling pathways involved in these processes. Our approaches include both genome-wide screening and targeted investigations.

We have discovered that bacterial proteins delivered into host cells by
Shigella modulate pathways involved in human cancers. We are defining how this occurs, with the long-term goal of applying insights gained in these investigations to the development of new cancer therapeutics.

Inside the host cell cytoplasm,
Shigella polymerizes host cell actin into a propulsive tail at one end of the bacterial body. Assembly of this tail generates the force to propel the bacterium to the cell periphery. A remarkable characteristic of the Shigella actin assembly protein (IcsA) is its localization to the old pole of the bacterium. Secretion of proteins and their precise spatial positioning is key to many cellular functions in prokaryotes; however, as yet, the basic mechanisms that mediate this positioning remain largely unknown. We are characterizing the molecular mechanisms of secretion and spatial positioning of proteins in bacteria. In addition, we are collaborating with Drs. Deb Hung and David Weiss to use state-of-the-art RNA technology and microfluidics in the development of novel rapid diagnostics for infectious diseases.



Last Update: 8/4/2015



Publications

For a complete listing of publications click here.

 


 

Garza-Mayers AC, Miller KA, Russo BC, Nagda DV, Goldberg MB. Shigella flexneri regulation of ARF6 activation during bacterial entry via an IpgD-mediated positive feedback loop. mBio. 2015. 6(2). pii: e02584-14. PMCID: PMC4358011.

Yi C-R, Allen JE, Russo B, Lee SY, Heindl JE, Baxt LA, Herrera BB, Kahoud E, MacBeath G,
Goldberg MB. Systematic analysis of bacterial effector-postsynaptic density 95/discs large/zonula occludens-1 (PDZ) interactions demonstrates Shigella OspE promotes PKC activation via PDLIM proteins. J Biol Chem. 2014; 289:30101-30113. PMCID: PMC4208017

Baxt LA,
Goldberg MB. Host and bacterial proteins that repress recruitment of LC3 to Shigella early during infection. PLoS One. 2014; 9(4):e94653. PMCID: PMC3983221

Li Z, Boyd D, Reindl M,
Goldberg MB. Identification of YidC residues that define interactions with the Sec apparatus. J Bacteriol. 2014; 196:367-377. PMCID: PMC3911256



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