- Development of protein-based biomarkers for colorectal cancer early detection.
- Biomarker applications and therapeutic utility of CEMIP in colorectal cancer
- Application of 15-PGDH as a biomarker for colorectal cancer risk and response to aspirin chemoprevention
- Determining the efficacy of CEMIP and 15-PGDH as therapeutic targets in inflammatory bowel disease
My research career has focused on understanding the mechanisms of colorectal cancer (CRC) initiation and progression as well as translational research of CRC. Current studies in the laboratory focus on two areas of translational research concerning 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) and Cell Migration-Inducing Hyaluronan Binding Protein (CEMIP): determining the utility of 15-PGDH and CEMIP as CRC biomarkers, and as novel therapeutic targets for treatment of CRC and/or inflammatory bowel disease (IBD). Some of our achievements to date include: a) demonstrating that colonic 15-PGDH levels are stable across distance and time and are not perturbed by aspirin intervention, thus suggesting 15-PGDH represents an independent target for modulation by candidate colon tumor chemopreventive agents; b) Identifying germline genetic variants in the 15-PGDH pathway that reduce colon 15-PGDH expression or function and are associated with increased CRC risk; c) Discovering that patients with low 15-PGDH levels are resistant to the chemopreventive effects of celecoxib and aspirin; and d) a co-first author paper published in Science discovering that 15-PGDH regulates tissue stem cell proliferation following tissue damage in the colon, which may have applications as a novel therapy the treatment of IBD. Currently, we are determining if 15-PGDH levels can either identify individuals at increased CRC risk, or individuals who will respond to aspirin chemoprevention.
Our studies on novel biomarker development have resulted in the discovery of CEMIP as a secreted protein highly induced in CRC and as a strong prognostic marker poor outcome in stage II/III CRCs. Furthermore, genetic deletion of CEMIP inhibits tumor growth and alters hyaluronan metabolism, indicating an important role in tumor phenotype and extracellular matrix remodeling. We are now interested in determining the utility of CEMIP as a prognostic and/or early diagnostic marker of CRC and its potential as a therapeutic target not only in CRC treatment, but possibly in IBD as well.