Gabriele Fuchs

Fuchs Lab website

Areas of Interest

• Ribosome composition in cells during stress and viral infections
• Ribosome subpopulations regulating translation
• Mechanism of  translational regulation in mammalian cells
• Translational control in cancer cells

Research

Ribosomes are found in all organisms and are essential for survival and growth. They are large complexes composed of RNA and protein molecules, and translate the mRNA sequence into a protein sequence.

Until recently it was thought that all ribosomes within one organism were identical. However, mass spectrometry analysis revealed that ribosomes within one organism, even within one single cell differ in posttranslational modifications and ribosome-associated proteins. Although many ribosome modifications have been identified, the impact these modifications have on protein biosynthesis is not clear.

My lab is interested in the following questions:

How is ribosome composition altered in cells during stress and during a viral infection?
How does ribosome composition regulate how much and which proteins are synthesized?
Are ribosomes in cancer cells different from ribosomes in healthy cells?
Can we use ribosome modifications to identify novel biomarkers for early cancer detection?

My lab uses cellular and molecular biology, biochemistry, virology as well as biophysical tools to decrypt the ribosome code.  We use mass spectrometry to identify ribosome modifications. To manipulate ribosome modifications and investigate how they alter translation of specific mRNAs we deplete known and putative modifying enzymes using siRNAs. Lastly, in addition to biochemical methods my lab will use single-molecule techniques to study how these modifications affect the function of the ribosome.

Publications

• NCBI Publications, Web resource, 2015
• “Kinetic pathway of 40S ribosomal subunit recruitment to hepatitis C virus internal ribosome entry site.” Fuchs G, Petrov AN, Marceau CD, Popov LM, Chen J, O'Leary SE, Wang R, Carette JE, Sarnow P, Puglisi JD. Proc Natl Acad Sci U.S.A. 2015 Jan 13;112(2):319-25. doi: 10.1073/pnas.1421328111. Epub 2014 Dec 16. PMID: 25516984, PMCID: PMC4299178 
• “Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension.” Sawada H, Saito T, Nickel NP, Alastalo TP, Glotzbach JP, Chan R, Haghighat L, Fuchs G, Januszyk M, Cao A, Lai YJ, Perez Vde J, Kim YM, Wang L, Chen PI, Spiekerkoetter E, Mitani Y, Gurtner GC, Sarnow P, Rabinovitch M. J Exp Med. 2014 Feb 10;211(2):263-80. doi: 10.1084/jem.20111741. Epub 2014 Jan 20. PMID: 24446489, PMCID: PMC3920564.
• “Proteomic analysis of ribosomes: translational control of mRNA populations by glycogen synthase GYS1.” Fuchs G, Diges C, Kohlstaedt LA, Wehner KA, Sarnow P. J Mol Biol. 2011 Jul 1;410(1):118-30. doi: 10.1016/j.jmb.2011.04.064. Epub 2011 May 5. PMID: 21570405, PMCID: PMC3131224.
• “MicroRNA-mediated gene silencing.” Pager CT, Wehner KA, Fuchs G, Sarnow P. Prog Mol Biol Transl Sci. 2009;90:187-210. doi: 10.1016/S1877-1173(09)90005-9. Epub 2009 Oct 27. Review. PMID: 20374742.
• “The subcellular distribution of an RNA quality control protein, the Ro autoantigen, is regulated by noncoding Y RNA binding.” Sim S, Weinberg DE, Fuchs G, Choi K, Chung J, Wolin SL. Mol Biol Cell. 2009 Mar;20(5):1555-64. doi: 10.1091/mbc.E08-11-1094. Epub 2008 Dec 30. PMID: 19116308, PMCID: PMC2649258. 
• “Structural and biochemical basis for misfolded RNA recognition by the Ro autoantigen.” Fuchs G, Stein AJ, Fu C, Reinisch KM, Wolin SL. Nat Struct Mol Biol. 2006 Nov;13(11):1002-9. Epub 2006 Oct 15. PMID: 17041599 
• “Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity.” Stein AJ, Fuchs G, Fu C, Wolin SL, Reinisch KM. Cell. 2005 May 20;121(4):529-39. PMID: 15907467 PMCID: PMC1769319. 
• “An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5.” Fernandez CF, Pannone BK, Chen X, Fuchs G, Wolin SL. Mol Biol Cell. 2004 Jun;15(6):2842-52. Epub 2004 Apr 9. PMID: 15075370, PMCID: PMC420107.