The laboratory of Dr. Leslie Poole applies chemical, cellular and biophysical approaches to better understand enzyme structure and function related to antioxidant enzymes that rely on cysteine residues. These approaches are also used to address redox regulation in specific cysteine-containing proteins that function in signal transduction pathways modulated by signaling-related (or damaging) oxidants like hydrogen peroxide, peroxynitrite and hypochlorous acid. The overarching goal is to understand physiological and pathological processes regulated by redox modifications, leading to better diagnostic, prognostic and treatment-related approaches to combat cancer, cardiovascular and neurodegenerative diseases, diabetes and more.
Innovative projects in the Poole laboratory and with team members include four major topics:
- Molecular studies of thiol-based peroxidases, especially peroxiredoxins (serving as antioxidants and signaling transduction mediators), as well as signaling-related proteins (e.g. ERK2) regulated by redox modifications.
- Evaluation of locations and extent of protein oxidation in cells through imaging and proteomics analyses using multiple approaches, particularly using chemical tools developed by our research team to irreversibly “trap” and detect protein sulfenic acids.
- Evaluation of efficacy and mechanisms involved in protection against the cardiotoxic effects of chemotherapeutics like doxorubicin, particularly by small molecules like dietary nitrate and hydrogen sulfide.
- Generation and optimization of cyanobacteria containing high levels of stearidonic acid (SDA), an omega-3 fatty acid that is more stable than, but serves as a precursor of, health beneficial omega-3 fatty acids EPA and DHA. The goal is to provide a CO2- and light-derived source of dietary omega-3s (for agricultural, aquacultural and human nutritional purposes) that will slow depletion of ocean fisheries plundered for fish oil and krill oil.
Methods and approaches developed during the course of these studies are applicable to a wide range of biological and pathophysiological systems. Many collaborative projects have been spawned through these innovations and Dr. Poole’s group actively participates in numerous team science projects, supported by pilot or federal research grants and patents.