The National Institutes of Health (“NIH”) has selected The Burnham Institute to develop a national resource for medical researchers to be known as the “Center on Proteolytic Pathways”. A team directed by The Burnham’s Jeffrey Smith, Ph.D., will receive $18.2 million over the next five years to develop this unique research hub.
The Center will consolidate all known and emerging knowledge about how proteins behave into “The Protease Pathway Interrogation Platform (‘PIPP’)”. The platform, PIPP, will be the product of a multi-disciplinary team, including the Burnham Institute’s Guy Salvesen, Ph.D., an expert on proteases and co-director of the center; Alex Strongin, Ph.D., a Professor at the Institute’s Inflammation and Infectious Disease Center; Adam Godzik, Ph.D., Director of the Institute’s Systems Biology Program, and Andrei Osterman, Ph.D., Associate Professor in that same program. Collaborators on this effort include Drs. Mathew Bogyo from Stanford University, Bonnie Sloane of Wayne State University, and Lisa Coussens from the University of California at San Francisco.
Why study proteolytic pathways? Proteolysis, or how proteins break down, regulates the four fundamental aspects of cell behavior: division, death, differentiation, and motility. Understanding this process is critical to designing new therapies based on promoting or inhibiting cellular behaviors.
A particular strength of the Center is its emphasis on the use of activity-based proteomics to profile protease function. This approach, developed by Dr. Bogyo at Stanford, marks an innovation over other proteomics strategies because the activity-based approach reports on protease activity, as opposed to just abundance.
In practical terms, Dr. Smith envisions that technology developed within the Center “should ultimately help define the physiologic and pathophysiologic role of every human protease.” Equally as significant, the Center will devise computational methods for predicting the behavior of entire biochemical pathways that connect to proteases.
Another outcome of research at the Center will be the development of a platform for screening small molecular libraries against all proteases encoded by the genome. Indeed, earlier this spring, Dr. Smith published results in the journal Cancer Research from his first proteomics-based assay which yielded the surprising result that Orlistat, a drug approved by the FDA for treatment of obesity, inhibited prostate cancer.