Scholars / Cancer Genomics

Cancer is a disease of gene mutation. Understanding these mutations that drive cancer leads to a better awareness of how cancer arises and spreads to distant organs.

Mark Burkard, MD, PhD

The UW Molecular Tumor Board: reading the unique fingerprint of each individual cancer.

The UW Molecular Tumor Board is a state-wide clinical service and research resource. The tumor board is a collaborative effort that virtually and physically brings together investigators in medical oncology, radiation oncology, pathology, molecular pathology and genetics, as well as colleagues at cancer delivery sites around the state including Gundersen, Aurora, Marshfield, ThedaCare, Fox Valley Hematology Oncology, and ProHealth. The tumor board serves as a resource to evaluate the meaning and context of genomic information about a patient’s tumor. After reviewing the clinical case, histopathology, and genomic information, the molecular tumor board develops a recommendation for a precision clinical trial or off-label medication individualized for the patient, in accordance with a pre-established guidance document. Over the next year this collaborative program plans will expand the reach of the tumor board to other sites around Wisconsin including Aspirus, Mercy/Janesville and Columbia St. Mary’s, to build resources for data sharing, and to pilot investigations of unusual cases.

John Denu, PhD

Dr. Denu’s research program centers on targeting DNA as a strategy to kill cancer cells.

Dr. Denu is embarking on a new project to determine strategies for targeting the oncogenic protein NSD2 as a therapeutic intervention in prostate cancer. NSD2 is an activator of gene expression that methylates Lysine-36 on Histone H3 (H3K36), and aberrant activity of NSD2 is implicated in more than 20 cancers and developmental disorders. Mutations lead to increased NSD2 methylation activity at H3K36 that are thought to dysregulate gene expression and promote tumorigenesis. New evidence suggests NSD2 may also be a driver in prostate cancers. NSD2 represents an excellent candidate for cancer therapies, however existing inhibitors display poor affinity and specificity. Understanding the biochemical properties of NSD2 will greatly facilitate the development of small-molecule inhibitors. Here the regulation of NSD2 methylation on H3K36 will be determined, and the chromatin-binding modules of NSD2 required to interact with nucleosomes and enhance H3K36 methylation will be identified.