Urban, a ‘fearless young scientist’
in protease research

Published April 03 2017

Siniša (Sin) Urban

“The privilege of curiosity-driven research is its own reward, but I’m truly honored to have our work recognized in this way by our ASBMB colleagues and friends. This is especially inspiring for the younger members of our small and emerging intramembrane proteolysis field.”


Siniša (Sin) Urban, a professor of molecular biology and genetics at the Johns Hopkins University, received the American Society for Biochemistry and Molecular Biology’s Young Investigator Award for his work on elucidating the mechanisms of intramembrane proteases.

Urban’s research represents a relatively new field that has developed largely due to his work. “While many young faculty follow ‘hot’ trends, (Urban’s) work is rigorous and extraordinarily innovative in an area that he himself created,” Nobel laureate Carol Greider of the Johns Hopkins University said in her letter nominating Urban for the award.

Urban studies rhomboid proteins, a group of proteases present inside the lipid bilayer of cell membranes that cut other transmembrane proteins. In addition to characterizing the mechanisms of these unique enzymes, he also has identified roles for rhomboid proteases in protozoal pathogens. “Very few investigators work at the intersection of these difficult areas,” explained Greider, “but what is clear from Dr. Urban’s work is that it is an area of great current and future importance.”

Despite being early in his career, Urban already has made numerous contributions to his field. Urban discovered and described the molecular function of the classical rhomboid gene during his graduate training in the Medical Research Council Laboratory of Molecular Biology in the U.K. For this discovery he has been awarded many prizes, including the Sandler Prize by the Genetics Society of America. Urban continued his work as a J.B. & Millicent Kaye Prize fellow in cancer studies in Cambridge before moving to Harvard University as a fellow for the Society of Fellows.

In 2006, he was recruited to the Johns Hopkins University, where he has expanded his work of revealing the molecular basis of rhomboid function and its role in disease. He has published papers in various journals, including Cell, Nature and Molecular Cell, that define the structure of rhomboid enzymes and describe a novel method to study enzyme kinetics in the membrane in real time. “He decided that achieving a real understanding of intramembrane enzymes required developing cutting edge biophysical approaches that were absent in his field,” said Greider. For this work, Urban also was named a Blavatnik Foundation scholar and a fellow of the Packard Foundation.

These systems have allowed Urban better to investigate how intramembrane proteases function. He has proposed a mechanism that is driven by kinetics and not substrate binding affinity. This represents a paradigm shift in the understanding of this class of enzymes, which previously had been assumed to act in an affinity-specific manner.

Urban also investigates the role of rhomboid proteases in medically relevant parasites, such as those that cause malaria. Protozoal diseases are enormous health burdens and often lack adequate treatments. His research on the role of rhomboid proteases in disease progression represents a promising area for development of novel protozoal treatments.

Urban is a hands-on scientist and “spends half his time at the bench” according to Greider. He also “devotes time to teaching and mentoring, including serving as Director of Admissions for the Johns Hopkins Biochemistry, Cell, and Molecular Biology (BCMB) PhD program at the School of Medicine,” said Greider, adding that Urban “will continue to contribute breakthroughs to our scientific community here and abroad.”

Urban will receive his award during the 2017 ASBMB Annual Meeting in Chicago, where he will deliver an award lecture. The presentation will take place at 9:15 a.m. April 24 in room W183ab in McCormick Place.

Courtney Chandler Courtney Chandler is a graduate student at the University of Maryland, Baltimore.