Uncovering a New Ubiquitin-Dependent Mechanism to Enhance IFN-a Efficacy in Myeloproliferative Neoplasms

Dr. Melo-Cardenas is focused on a group of blood cancers called myeloproliferative neoplasms (MPNs), which cause the body to produce too many abnormal blood cells. MPNs are driven by genetic mutations that keep growth and inflammatory signals permanently switched on, allowing cancerous blood cells to survive and expand. There are current treatments available to alleviate symptoms, but these treatments are rarely able to eliminate cancer or stop disease progression.

Dr. Melo-Cardenas has found that a protein called DCAF7, which helps control how proteins are degraded when they are no longer needed, is present at high levels in MPNs and is required for growing MPN cells. When DCAF7 is removed, a protein involved in interferon signaling becomes more stable slowing cancer growth. Currently there are therapies for MPNs using interferons that can reduce the number of cancerous mutated cells in the blood, but response is uneven and complete response only occurs in a subset of patients. Dr. Melo-Cardenas suspects that by inhibiting DCAF7, doctors may be able to enhance the effectiveness of interferon therapy in MPN patients. Using her CRF Young Investigator Award, Dr. Melo-Cardenas will first attempt to fully elucidate what role DCAF7 plays in regulating interferon signaling in MPN. She will then use both mouse and human derived cell models to see if blocking or reducing DCAF7 might make interferon therapy more effective. She hopes to find that DCAF7 will prove to be a druggable target that can make a significant impact for patients suffering from MPN.