Professor of Medicine, Division of Hematology/Medical Oncology, School of Medicine
Associate Dean, Oncology, Office of the Dean, School of Medicine
Director OHSU Knight Cancer Institute School of Medicine
JELD-WEN Chair of Leukemia Research
Cancer Biology Graduate Program, School of Medicine
Program in Molecular and Cellular Biosciences, School of Medicine
Oregon Health & Science University (OHSU)
Dr. Druker's research focuses on activated tyrosine kinases with an emphasis on signal transduction and cellular transformation and the application of this knowledge to cancer therapies. The BCR-ABL oncogene is his lab's primary model system because of its central role in the pathogenesis of a human disease, chronic myeloid leukemia (CML). Numerous tyrosine phosphorylated proteins have been identified in BCR-ABL transformed cells and projects are ongoing to define their necessity for BCR-ABL function. These studies include mutational, biochemical and genetic approaches. Imatinib (Gleevec), a specific inhibitor of the ABL protein tyrosine kinase, has been proven to be an effective therapeutic agent in CML. However, it is not capable of eliminating all leukemic cells. In laboratory correlate studies done alongside imatinib clinical trials, Dr. Druker's lab learned that ABL kinase domain mutations are the most common mechanism of resistance to imatinib. Using this information, his team has evaluated several novel ABL inhibitors that are now available to treat patients with Gleevec resistance. Lastly, Dr. Druker's lab is performing screens for other tyrosine kinases that may be pathogenic in other leukemias and has developed functional assays that allow rapid target identification.
Professor, Department of Pediatrics
Associate Member, Department of Medicine, Division of Experimental Medicine
Dr. Jabado has embarked on elucidating genetic signatures of pediatric astrocytomas and examining how they compare to adults. These are deadly brain tumours that originate in brain and include glioblastomas (GBM, the highest grade of astrocytomas), which are one of the deadliest cancers in humans. Her group uncovered that pediatric high-grade astrocytomas (HGA) are molecularly and genetically distinct from adult tumors. They also identified a new molecular mechanism driving pediatric HGA, namely recurrent somatic driver mutations in the tail of histone 3 variants (H3.3 and H3.1). These mutations lead to amino acid substitutions at key residues and are tightly correlated with a distinct global DNA methylation pattern, neuroanatomical locations and age specificities. Their findings position them as leaders in the field of HGA, at the forefront of significant breakthroughs for this deadly brain tumor. Crucial impediments to progress are the lack of reliable in vitro and in vivo models for these “oncohistones” and understanding their effects in driving tumors and therapeutic resistance. they aim to identify events affected downstream of each mutation, and validate targets in their new models to better advise the use of experimental or pipeline drug(s) or drug combinations that could be rapidly translated into clinical trials. Ultimately, based on their findings, patients could be stratified based on their genetic/molecular signature, and assigned to a beneficial therapeutic strategy, bringing needed effective interventions in this devastating cancer. Additionally, they established a TCGA-like initiative by creating the International CHildhood Astrocytoma INtegrated Genomic and Epigenomic (ICHANGE) Consortium. This is a unique set of resources which enables the scientific world to investigate astrocytomas in children. It includes databases and access to technology as well as international collaborations from 15 participating countries, including ~1500 annotated glioma tissue samples representative of all grades and ages.