John Jacob

John Jacob, FRCP PhD, is an Honorary Senior Clinical Research Fellow and Consultant Neurologist at the Nuffield Department of Clinical Neurosciences (NDCN), University of Oxford. A clinician-scientist with expertise in developmental neurobiology, he investigates how developmental abnormalities drive cancer pathogenesis, focusing on pediatric medulloblastoma as the most common malignant brain tumor in children.

His research centers on the sonic hedgehog (SHH) signaling pathway's role in growth, stem cell maintenance, and tumorigenesis. He pioneers human cellular models of SHH-medulloblastoma using CRISPR-engineered cerebellar organoids derived from human induced pluripotent stem cells (hiPSCs) to replicate tumor heterogeneity and microenvironment interactions. This work integrates advanced stem cell differentiation, single-cell sequencing, and computational analysis from the Big Data Institute to dissect molecular mechanisms underlying treatment resistance.

Recent publications demonstrate a cohesive trajectory in modeling medulloblastoma through cerebellar organoids, with emphasis on PTCH1 mutations, lipid metabolism's impact on hedgehog signaling, and tumor microenvironment dynamics. His approach bridges developmental neurobiology and oncology to develop personalized therapeutic strategies that address the debilitating side effects of current treatments.

Dr. Jacob has secured competitive funding from the Wellcome Trust, Medical Research Council, Simons Foundation Autism Research Initiative, and Cancer Research UK Oxford. His collaborative network spans the NDCN, Sir William Dunn School of Pathology, and Big Data Institute, enabling cross-disciplinary innovation in neuro-oncology model systems and therapeutic discovery.