James M. Olson
M.D., University of Michigan, Medicine, 1991.
Ph.D., University of Michigan, Pharmacology, 1989.
B.S., Western Michigan University, Biomedical Science, Magna Cum Laude, 1984.
Dr. Olson's laboratory studies the gene expression programs controlling neural differentiation, brain tumor genesis, and neurodegenerative diseases. Translation of laboratory findings to clinical therapeutics is accelerated through an extensive network of academic and industry collaborations.
Pediatric Brain Tumors
Medulloblastoma is the most common malignant brain tumor of childhood. It arises from cerebellar granule cell precursors, in some cases through mutations that lead to excess signaling of the sonic hedgehog pathway. In a multi-institutional collaborative study, we showed that one type of medulloblastoma (desmoplastic histology) overexpresses genes that are downstream of hedgehog and that another type (classic histology) is notable for overexpression of a small group of genes including the transcription factor, neuroD3/neurogenin (Pomeroy, 2001). Based on these studies, we are generating new mouse models of medulloblastoma and testing candidate drugs that interfere with the aberrant signaling pathways. For the latter goal, we lead a national consortium for pre-clinical analysis of new compounds. So far, we have demonstrated efficacy of two drug classes, retinoids and cyclopamine derivatives (Hallahan, 2003; Berman, 2002). Both effectively induce apoptosis in medulloblastoma cells derived from patient surgical samples and in established medulloblastoma cell cultures. We elucidated the mechanism by which retinoids induce apoptosis, providing a basis for understanding why some cells are sensitive to this agent and others are resistant. Based on these data, we are developing a national Phase III clinical trial through the Children’s Oncology Group to assess the efficacy of retinoids in children with high risk medulloblastoma/primitive neuroectodermal tumor.
Dr. Olson is the author of “Clinical Pharmacology Made Ridiculously Simple,” a textbook geared toward medical students making the transition from classroom pharmacology to clinical pharmacology. The principles of pharmacology and the relationships that we have developed in research divisions of pharmaceutical companies accelerate translation of our basic research into clinical practice.
Children's Oncology Group
Children's Oncology Group Brain Tumor Resource Laboratory
Hereditary Disease Array Group
Hereditary Disease Foundation Scientific Advisory Board
Society for Neuroscience
Honors and Awards
Damon Runyon Clinical Investigator Award,
Burroughs Wellcome Career Award in Biomedical Sciences,
Child Health Research Center New Investigator Award,
American Academy of Pediatrics Resident Research Award,
Emily Dorfman Fellow, American Brain Tumor Association,
2000-2004, Assistant Member, Fred Hutchinson Cancer Research Center, Clinical Research
HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma.. Cancer cell. 29(3):311-23.. 2016.
Successful Translation of Fluorescence Navigation During Oncologic Surgery: A Consensus Report.. Journal of nuclear medicine : official publication, Society of Nuclear Medicine.. 2015.
Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.. Cancer research. 75(20):4283-91.. 2015.
Image-Guided Tumor Resection.. Cancer journal (Sudbury, Mass.). 21(3):206-12.. 2015.
Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells.. Cell reports. 13(11):2425-39.. 2015.
A technology platform to assess multiple cancer agents simultaneously within a patient's tumor.. Science translational medicine. 7(284):284ra58.. 2015.
Early transcriptional profiles in huntingtin-inducible striatal cells by microarray analyses.. Human molecular genetics.. 2014.
Therapeutic opportunities for medulloblastoma come of age.. Cancer cell. 25(3):267-9.. 2014.
BuGZ Is Required for Bub3 Stability, Bub1 Kinetochore Function, and Chromosome Alignment.. Developmental cell. 28(3):282-94.. 2014.
Pemetrexed and Gemcitabine as Combination Therapy for the Treatment of Group3 Medulloblastoma.. Cancer cell. 25(4):516-29.. 2014.
Cytogenetic Prognostication Within Medulloblastoma Subgroups.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 32(9):886-96.. 2014.
Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group.. Acta neuropathologica. 127(2):189-201.. 2014.
MyoD Is a Tumor Suppressor Gene in Medulloblastoma.. Cancer research. 73(22):6828-37.. 2013.
Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A.. Genes & development. 27(9):1032-45.. 2013.
Canonical TGF-β Pathway Activity Is a Predictor of SHH-Driven Medulloblastoma Survival and Delineates Putative Precursors in Cerebellar Development.. Brain pathology (Zurich, Switzerland). 23(2):178-91.. 2013.
Fundamental differences in promoter CpG island DNA hypermethylation between human cancer and genetically engineered mouse models of cancer.. Epigenetics : official journal of the DNA Methylation Society. 8(12):1254-60.. 2013.
Prognostic value and functional consequences of cell cycle inhibitor p27Kip1 loss in medulloblastoma.. Biomarker research. 1(1):14.. 2013.
Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model.. Proceedings of the National Academy of Sciences of the United States of America. 109(20):7859-64.. 2012.
The molecular classification of medulloblastoma: driving the next generation clinical trials.. Current opinion in pediatrics. 24(1):33-9.. 2012.
Distinct Smoothened mutation causes severe cerebellar developmental defects and medulloblastoma in a novel transgenic mouse model.. Molecular and cellular biology.. 2012.
Subgroup-specific structural variation across 1,000 medulloblastoma genomes.. Nature. 488(7409):49-56.. 2012.
Cancer-specific requirement for BUB1B/BubR1 in human brain tumor isolates and genetically transformed cells.. Cancer discovery. 3(2):198-211.. 2012.
NeuroD factors regulate cell fate and neurite stratification in the developing retina.. The Journal of neuroscience : the official journal of the Society for Neuroscience. 31(20):7365-79.. 2011.