Dawn Quelle receives Oberley Seed Grant Award

Dawn Quelle received an Oberley seed grant award from the Holden Comprehensive Cancer Center to examine “Serotonin regulation by RABL6A in neuroendocrine tumors.”  Elevated serotonin is the major factor driving carcinoid syndrome (CS) in patients with metastatic small bowel neuroendocrine tumors (sbNETs).  Patients with CS suffer from extensive diarrhea, cutaneous flushing and sweating, and less frequently heart failure.  Currently, there are no molecular markers to predict which sbNET patients will develop CS or respond best to therapy with telotristat etiprate (TE), a drug that inhibits the essential enzyme (TPH1) in serotonin synthesis.  The Quelle lab may have identified a new biomarker of CS whose expression in tumors may predict response to TE therapy. They discovered that RABL6A, an oncogenic protein highly expressed in NETs, increases serotonin levels in NET cells by upregulating TPH1.  Parallel studies in the brains of RABL6A-deficient mice revealed RABL6A is essential for both TPH and serotonin expression in vivo.  Oberley grant funds will support analyses of the RABL6A-serotonin pathway in NET relevant systems, including enterochromaffin cells in the small bowel (which produce >90% of the body’s serotonin) and mouse models of NET disease.   

Thursday, April 9, 2020