Cancer cells rely on efficient uptake, conversion, and exchange of nutrients and vitamins to support their rapid growth and survival. The molecular transport channels that allow passage of nutrients between the different cellular compartments are critical for the survival of cancer cells and are thus promising as potential drug targets. However, drug discovery efforts are hampered by a lack of basic understanding of these channels' identities, functions, and regulation inside cancer cells. Dr. Kory's research aims to identify transporters central to cancer cell nutrient supply and detoxification pathways and determine their role in the emergence, survival, and aggressiveness of cancer. Her research is relevant to all cancers, but particularly pediatric, blood, and breast cancers.

Only up to 20% of patients with advanced ovarian cancer will survive five years after diagnosis. This is largely due to the cancer’s resistance to traditional chemotherapy and the current lack of targeted therapies that work with chemotherapy to improve response. Dr. Mullen’s lab has identified a new target, COP9 Signalosome Subunit 5 (COPS5), to treat ovarian cancer. Her team has found that inhibiting COPS5 with a drug called CSN5i-3 drastically improves ovarian cancer response to chemotherapy. She now aims to test the effectiveness of CSN5i-3 and chemotherapy against patient-derived, therapy-resistant ovarian cancer tumors. She will also investigate the mechanism of COPS5, believed to be involved in the repair of DNA damage caused by chemotherapy. Dr. Mullen hopes this innovative target will transform the care of patients with ovarian cancer.

Chromatin remodelers are complex protein machines responsible for packaging DNA and regulating gene expression. Their dysfunction is strongly implicated in cancer. For example, certain types of sarcoma and ovarian cancer are driven by mutations in a chromatin remodeler called BAF. Combining experiments with theoretical work, Dr. Owen’s research aims to understand how remodelers recognize their target sites in the cell’s nucleus. By expanding our understanding of chromatin remodeling, the findings of this research will provide the groundwork for more effective cancer treatments—suggesting how drugs might target chromatin remodelers—as well as enhance our understanding of how existing drugs that target remodeler-adjacent mechanisms might work.

A central aim of this project is the development of new, quantitative models to explain the behavior of chromatin remodelers seen in experiments. Dr. Owen will achieve this by successive rounds of passing between theory and experiments repeatedly—measuring, modeling, then measuring again. For comparison to experiments, model predictions will be extracted computationally (e.g., numerically solving ODEs, or by exact stochastic simulation using Gillespie’s algorithm) or analytically (e.g., by the King-Altman procedure, and variants), as appropriate.