How normal cell aging drives tumor progression and resistance to treatment.

Cancer doesn't appear in a vacuum — it grows more common as we age. Our lab investigates exactly why, at the cellular level, and what aging cells do to help tumors thrive.

The incidence of cancer increases with age. Our laboratory is interested in basic science understanding of normal cell aging and its impact on epithelial cancer progression and response to therapy. Replicative and chronological lifespans are two modes of normal cell aging. Because the majority of cells in vivo reside in quiescence, we focus on cellular and molecular mechanisms that regulate chronological lifespan. We have documented a significant role of mitochondrial antioxidant networks and morphology (fission and fusion) in regulating chronological lifespan of normal human fibroblasts. Critically, we have shown that normal cells nearing the end of their chronological lifespan promote progression and therapy resistance in epithelial cancers — with age-related increases in lipolysis playing a central role. We propose the lipolytic signaling pathway as a novel target for cancer therapy.

Redox biology of blood, platelets, and nutritional antioxidants in heart health.

The cardiovascular system is shaped by chemistry at every level — from how your blood platelets clot to how vitamin C and E protect your heart. Our faculty are working to understand and intervene at each of these points.

FRRB faculty are engaged in a broad range of studies aimed at better understanding the cardiovascular system. These range from blood platelet function and the fundamental redox properties of red blood cells to how nutritional antioxidants such as vitamins C and E function to maintain health. Ongoing work examines NADPH oxidase pathways in thrombosis, the gut-liver axis and metabolic syndrome, the heritability of glutathione levels in human erythrocytes, and the role of extracellular superoxide dismutase at the vitreoretinal interface.

How redox toxins — from environmental poisons to cancer drugs — affect cells.

Some of the most promising cancer treatments work by exploiting redox chemistry — but so do many dangerous toxins. Our labs investigate how oxidative mechanisms can be harnessed to kill tumors while protecting healthy tissue.

FRRB labs are involved in a wide range of studies addressing the redox toxicology of xenobiotics, ranging from environmental toxins to drugs used in cancer treatment. Many xenobiotics act as redox toxins, poisoning cellular processes by oxidative mechanisms. Current focus areas include pharmacological ascorbate as a sensitizer for radio-chemotherapy, artemisinin-derived compounds, disulfiram and copper redox cycling, selenium's role in cancer therapy, and innovative dosing metrics for cell culture. FLASH versus conventional dose rate irradiation is another active area of investigation.

Free radical biology in brain tumor resistance, heterogeneity, and new treatments.

Brain tumors like glioblastoma remain among the hardest cancers to treat. Our faculty investigate why — and are developing redox-based strategies that could change the odds for patients.

Our faculty are interested in brain tumors, focusing on many aspects of free radical biology in therapy resistance, the development of new therapeutic strategies, and tumor heterogeneity. Ongoing work includes investigating radioresistance in glioblastoma and the development of radiosensitizers, repositioning existing drugs such as chlorpromazine to overcome chemoresistance, and clinical trials combining pharmacological ascorbate with radiation and temozolomide for newly diagnosed glioblastoma.