Overview
In our lab, we seek to understand the mechanisms that are critical for maintaining the survival of the cancer stem-like cell population responsible for metastasis, treatment-resistance, and tumor recurrence in the most common malignant brain tumor of childhood, medulloblastoma. Overall, we hope to translate our findings to novel therapeutic strategies for this brain cancer.
Dr. MacDonald first reported the platelet-derived growth factor receptor (PDGFR)-RAS/MAPK signaling pathway in promoting medulloblastoma metastasis in 2001 (Nature Genetics). Since then, his lab has explored therapeutically targeting the PDGFR pathway, and subsequently discovered STAT3 as a critical PDGFR downstream mediator of survival signaling and metastasis in sonic hedgehog-driven medulloblastoma. This work was clinically translated by Dr. MacDonald into a Phase I first-in-child clinical trial with the STAT3 inhibitor WP1066 for relapsed pediatric brain cancers, which completed in Fall 2023. Dr. MacDonald is now developing national phase II trials for WP1066 as well as investigating other STAT3 and related inhibitors in combination for clinical application. Also, in collaboration with scientists at Georgia Tech, the MacDonald lab is: 1) developing assays to rapidly screen drug efficacy in real-time using patient brain tumor biopsy specimens; 2) investigating nanoparticles and focused ultrasound for delivery of RNA and immunotherapy to brain tumors; and 3) using Cluster-Wells nanochip to isolate circulating tumor cells in the blood and CSF of brain tumor patients.