Matthew Scott

Matthew Scott has made transformative contributions to understanding Hedgehog pathway-driven medulloblastoma, demonstrating that Patched1 (PTCH1) loss-of-function mutations constitutively activate Hedgehog signaling to drive the SHH subgroup of medulloblastoma which accounts for approximately 30% of all cases. His laboratory defined the spectrum of Hedgehog pathway mutations in medulloblastoma including PTCH1, SMO, SUFU, and GLI2 amplification. He elucidated mechanisms of resistance to Smoothened inhibitors including SMO mutations and GLI2 amplification that bypass Smoothened. His research has informed clinical strategies combining Smoothened inhibitors with downstream GLI targeting to overcome resistance.