BBS Faculty Member - Marcia Goldberg

Faculty Listing

Marcia Goldberg

Department of Microbiology and Immunobiology

Massachusetts General Hospital
HIM Building, Room 847
4 Blackfan Circle
Boston, MA 02115
Tel: 617-525-4820
Email: mgoldberg1@partners.org
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: 4/22/2021

Publications

For a complete listing of publications click here.

Russo BC, Stamm LM, Raaben M, Kim CM, Kahoud E, Robinson LR, Bose S, Queiroz AL, Herrera BB, Baxt LA, Mor-Vaknin N, Fu Y, Molina G, Markovitz DM, Whelan SP, Goldberg MB. Intermediate filaments enable pathogen docking to trigger type 3 effector translocation. Nat Microbiol. 2016. 1:16025. PMC5006386.

Russo BC, Duncan JK, Goldberg MB. Topological analysis of the type 3 secretion system translocon pore protein IpaC following its native delivery to the plasma membrane during infection. mBio. 2019 May 28;10(3). pii: e00877-19. doi: 10.1128/mBio.00877-19.

Russo BC, Duncan JK, Wiscovitch AL, Hachey AC, Goldberg MB. Activation of Shigella flexneri type 3 secretion requires a host-induced conformational change to the translocon pore. PLoS Pathog. 2019; 15:e1007928.

Reyes M, Filbin MR, Bhattacharyya RP, Billman K, Eisenhaure T, Hung DT, Levy BD, Baron RM, Blainey PC#, Goldberg MB#, Hacohen N#. An immune cell signature of bacterial sepsis. Nat Med. 2020 Mar; 26(3):333-340. doi: 10.1038/s41591-020-0752-4. #Co-corresponding authors.

Shrock E, Fujimura,…Goldberg MB, et al. Viral epitope profiling in COVID-19 patients reveals cross-reactivity and correlates of severity. Science. 2020 Nov 27; 370(6520):eabd4250. doi: 10.1126/science.abd4250.

Kutsch M, Sistemich L, Lesser CF, Goldberg MB, Herrmann C, Coers J. Direct binding of polymeric GBP1 to LPS disrupts bacterial cell envelope functions. EMBO J. 2020; 39(13):e104926. PMC7327485

Duncan-Lowey JK, Wiscovitch AL, Wood TE, Goldberg MB#, Russo BC#. Shigella flexneri disruption of cellular tension promotes intercellular spread. Cell Rep. 2020; 33, 108409. Nov. 24. Accepted. #Co-corresponding authors.

Filbin MR, Mehta A, …., Hacohen N, Goldberg MB. Plasma proteomics reveals tissue-specific cell death and mediators of cell-cell interactions in severe COVID-19 patients. Cell Rep Med. doi: 10.1101/2020.11.02.365536.