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Sinisa Urban, Ph.D.

Photo of Dr. Sinisa Urban, Ph.D.

Professor of Molecular Biology and Genetics

Research Interests: Intra-membrane proteases in cell signaling and microbial pathogenesis; Rhomboid enzymes

Background

Dr. Sinisa Urban is an associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine. His work examines the biochemistry, cell and chemical biology of intra-membrane proteases in cell signaling and microbial pathogenesis.

Dr. Urban obtained his B.S. in genetics at the University of Alberta, where he studied DNA replication using bacteriophage T4 and Hepatitis B virus. He received his Ph.D. from the University of Cambridge, where he focused on developmental signaling at the Medical Research Council (MRC) Laboratory of Molecular Biology. There he discovered that the classical Drosophila developmental regulator rhomboid functions as an intramembrane protease.

He continued to study rhomboid mechanism as a JB & Millicent Kaye Prize Fellow of Christ’s College at the University of Cambridge, before moving to Harvard Medical School in the fall of 2003. He joined the faculty of Johns Hopkins in 2006.

Dr. Urban has received over 40 awards for his work, including the Genetics Society of America’s Sandler Award for Most Outstanding International Ph.D. Dissertation, Oxford’s Rolleston and MRC’s Max Perutz Prizes for Original Research, Her Royal Highness the Princess of Wales’ Canada Scholarship for AIDS Research and the Cambridge Gedge Prize for Outstanding Observations in Physiology.

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Titles

  • Professor of Molecular Biology and Genetics

Departments / Divisions

Education

Degrees

  • Ph.D., University of Cambridge (United Kingdom) (2002)

Additional Training

Christ's College, Cambridge University, Cambridge, UK, 2003, Molecular Biology; Harvard University Medical School, Boston, MA, 2004, Molecular Biology

Research & Publications

Research Summary

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.

Dr. Urban’s laboratory studies the biochemical principles governing how rhomboid enzymes catalyze reactions immersed within the membrane. They have reconstituted rhomboid activity with pure components, and are using a combination of membrane biochemistry, cell biology and chemical genetics to probe their mechanism.

Another research focus is on rhomboid function in deadly human pathogens. His lab 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 amoeba uses its rhomboid in phagocytosis and immune evasion. Targeting rhomboid enzymes ultimately may be a way of treating multiple infectious diseases.

Lab Website: Urban Lab

Selected Publications

Dickey SW, Baker RP, Cho S, and Urban S. "Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity." Cell. 2013 Dec; 155(6): 1270-1281.

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

Zhou Y, Moin SM, Urban S and Zhang Y. "An internal water-retention site in the rhomboid intramembrane protease GlpG ensures catalytic efficiency." Structure. 2012 July; 20(7): 1255-1263.

Parussini F, Tang Q, Moin SM, Mital J, Urban S, and Ward GE. "Intramembrane proteolysis of Toxoplasma aplical membrane antigen 1 facilitates host-cell invasion but is dispensable for replication." Proc. Natl. Acad. Sci. USA. 2012; 109 (19): 7463-7468.

Baker RP and Urban S. "Architectural and thermodynamic principles underlying intramembrane protease function." Nature Chemical Biology. 2011 Dec.; 8(9): 759-768. (DOI 10.1038/nchembio.1021)

Academic Affiliations & Courses

Graduate Program Affiliation

Biochemistry, Cellular and Molecular Biology (BCMB) Graduate Program

Activities & Honors

Honors

  • Sandler Award for Most Outstanding International Ph.D.¬†Dissertation, Genetics Society of America
  • Canada Scholarship for AIDS Research, Her Royal Highness the Princess of Wales
  • Max Perutz Prizes for Original Research, Medical Research Council
  • Rolleston Prize for Original Research, Oxford University
  • Gedge Prize for Outstanding Observations in Physiology, the University of Cambridge
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