Metabolism, MRI, Spectroscopy, Cancer, Neurodegeneration, Drug Resistance, Aging, Oxidative Stress; Microdevices, Tumor Microenvironment, Mass Spectrometry
Our laboratory is focused upon using engineering and chemical analysis to study oxidative stress in cultured cells and intact tissue. Oxidative stress is present in almost all human pathologies and our lab is focused on its role in the development and treatment of cancer and neurodegenerative processes. Projects underway include:
Evaluating static and dynamic hypoxia on drug response in cancer.
With Dr. Glenn Walker, we are developing a novel high-throughput multiwell device that can culture cell lines under different static and dynamically changing oxygen atmospheres on a single plate. This enables studies of cell growth, proteomics, metabolomic, genomic and drug response under various levels of static and dynamically changing hypoxic conditions. Both chronic and cycling hypoxia occur in patient tumors and induce oxidative stress in tissue yet most drug screening is performed in air/CO2 incubators. We expect drug response to be radically altered by the hypoxic conditions and this technology will provide a more relevant model for screening anticancer drugs.
Oxygen-driven Metastasis of Cancer
We are studying the impact of oxygen gradients on cell invasion in a microdevice-based model of cancer metastasis. With Dr. Walker, we have developed a multilayered microdevice to follow cancer cell migration, invasion and intravasation. Research has shown oxidative stress increases in cells exposed to chronic hypoxia and induces metastasis. These effects are exacerbated in cells exposed to cycling hypoxia. Our technology enables us to determine the effects of oxygen conditions on metastatic potential in cancer. We can use this tool to develop antimetastatic drugs.
Dynamic Studies of Redox Metabolism
The laboratory has long been interested in studying the rates of metabolism of the cellular antioxidant glutathione and one carbon metabolism in cancer and brain tissue. We have found that the dynamics or rates of metabolism are better measures of tissue response than static measures provided by metabolomic, proteomic or genomic studies. We use stable isotope tracer technology combined with magnetic resonance and mass spectrometry to obtain kinetic data on metabolic pathways. Working with Drs. Jeff Macdonald and Shawn Gomez, we are using these data and a systems biology approach to develop a mathematical model of redox metabolism in cancer. This approach will help predict the behavior of complex systems and identify emergent properties that cannot be easily inferred from studies of components in isolation.