Research

By its very nature, exploratory research is high risk and high return. This means researchers must know what projects need to be started and what projects need to end. When the CIWHR joined the Division of Trauma, Surgical Critical Care and Burns in 2007, its scientific team refocused its basic research in combinatorial display, genetic re-engineering of growth factors and protease regulation to ask one central question: What is the biology that drives the injury to the path of resolution?

Sentinel genes and Set Points of Homeostasis: The clinical team at UCSD first identified what they believed was the over-arching global problem in the treatment of injury. What drives injury resolution? In partnership with the basic scientist team, they developed the "sentinel hypothesis" and proposed that the genome must encode secreted factors (secretome) that monitor and maintain the set point that defines an individual's normal homeostasis. The research group set out to uncover and characterize these sentinel factors.

Sentinel gene discovery and deployment: Using advanced modern molecular screening tools of genomics, proteomics, epigenomics and bioinformatics, the CIWHR research group defined sentinel genes as (1) encoding secreted proteins and thus part of the secretome, (2) resembling ligands and thus part of the neuropeptidome, (3) controlled by the environment and thus epigenetically regulated and (4) constitutively expressed in normal tissues but (5) down regulated in injury. The team identified several prototypic candidate sentinel gene in orphan open reading frames and these are the focus of the research teams and we ask: (1) what are they and what do they do? (2) how are they regulated and can they be controlled? (3) can they serve to forecast the outcome after injury and predict resolution? And finally (4) can they be developed as biotherapeutics and deployed in the treatment of injury repair.