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Sin Urban - Professor
Molecular Biology & Genetics

725 N. Wolfe Street
507 PCTB
Baltimore, MD 21205

Office: 410-502-6247


Assistant: Cynthia Rogers
Biochemistry, cell and chemical biology of intra-membrane proteases in cell signaling and microbial pathogenesis
Cell membranes are sites of interface between the cell and the outside world, and constitute major sites of signaling. Membranes also form the front lines where deadly pathogens first contact human cells and initiate infection. Our main focus is a family of membrane-immersed enzymes, termed rhomboid proteases, which catalyze a biochemical reaction that cuts protein segments within the membrane. This cleavage liberates proteins from the membrane, either to activate signals rapidly, or to inactivate other targets. Because of its speed and versatility, this basic biochemical reaction has evolved to control many cellular processes in all forms of life, from diverse bacteria to humans. But how these enzymes achieve catalysis within the membrane, and their roles in all but a few organisms, remain unclear.
We study the biochemical principles governing how rhomboid enzymes catalyze reactions immersed within the membrane. We have reconstituted rhomboid activity with pure components, and are using a combination of membrane biochemistry, cell biology and chemical genetics to probe their mechanism. We have also focused on rhomboid function in deadly human pathogens, and discovered that rhomboid enzymes execute an array of essential functions: malaria and related parasites use their rhomboid enzymes to invade human cells, while a parasitic ameba uses its rhomboid in phagocytosis and immune evasion. Targeting rhomboid enzymes may be a way of treating multiple infectious diseases.
Relevant Publications:

Baker R.P. and S. Urban. Cytosolic extensions directly regulate a rhomboid protease by modulating substrate gating. (2015). Nature 523(7558): 101-105.  (DOI: 10.1038/nature14357)
Link to Article

Urban S., Moin S.M. A subset of membrane-altering agents and γ-secretase modulators provoke nonsubstrate cleavage by rhomboid proteases. (2014). Cell Reports 8(5):1241-1247. doi: 10.1016/j.celrep.2014.07.039.
Link to Article

Dickey S.W., Baker R.P., Cho S., and  S. Urban. Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity. (2013). Cell, 155(6): 1270-1281.
Link to Article

Moin S. and S. Urban. Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics. (2012). eLife, 1: e00173. (DOI 10.7554/eLife.00173)
Link to Article

Baker R.P. and S. Urban. Architectural and thermodynamic principles underlying intramembrane protease function. (2012). Nature Chemical Biology 8(9): 759-768. (DOI 10.1038/nchembio.1021)
Link to Article

Urban, S. and Dickey S.W. The rhomboid protease family; a decade of progress on function and mechanism. (2011). Genome Biology, 12(10): 231-41.
Link to Article

Urban, S. Making the cut: central roles of intramembrane proteolysis in pathogenic microorganisms (2009). Nature Reviews Microbiology 7: 411-423 [cover article]
Link to Article

Baxt, L.A., Baker R.P., Singh U., and S. Urban. An Entamoeba histolytica rhomboid protease with atypical specificity cleaves a surface lectin involved in phagocytosis and immune evasion. (2008). Genes & Development 22(12): 1636-1646. [cover article]
Link to Article

Baker, R.P., Young K., Feng L., Shi Y. and S. Urban. Enzymatic analysis of a rhomboid intramembrane proteases implicates transmembrane helix 5 as the lateral substrate gate. (2007). Proc. Natl. Acad. Sci. USA. 104 (20): 8257-8262. [cover article]
Link to Article

Baker, R.P., Wijetilaka R, and S. Urban. Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria. (2006). PLoS Pathogens. 10(2): e113.
Link to Article
Brossier F., Jewett T., Sibley D. L., and S. Urban. A spatially-localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. (2005). Proc. Natl. Acad. Sci. USA. <102(11):4146-4151.
Link to Article
Urban, S. and M. S. Wolfe. Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. (2005). Proc. Natl. Acad. Sci. USA. 102(6):1883-1888.
Link to Article
Urban, S. and M. Freeman. Substrate specificity of Rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain. (2003). Molecular Cell. 11: 1425-1434.
Link to Article
Urban, S., Lee J. R., and M. Freeman. A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF-like ligands (2002). EMBO Journal. 21: 4277-4286.
Link to Article
Urban, S., Lee J. R., and M. Freeman. Drosophila Rhomboid-1 defines a family of putative intramembrane serine proteases. (2001). Cell. 107 (2): 173-182.
Link to Article
Graduate Program AffiliationsBiochemistry, Cellular & Molecular Biology (BCMB)


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