Toxicology, a major branch of pharmacology, is focused on the adverse effects of chemicals on humans and other living organisms. Such chemicals can include established pharmaceutics, experimental/developmental drugs and nonoparticles. Other chemicals of interest include environmental pollutants, such as volatile hydrocarbons and environmental oxidants. Our faculty is actively engaged in research projects with a focus on the ability of these agents to include multiple pathologies including cancer, neurodegenerative disease, infectious disease, cardiovascular disease, and muscular dystrophies.
Faculty members & their research interests
Dr. Bruckner’s main focus of ongoing research is on basic toxicology and pharmacokinetic questions that impact assessments of risks of chemicals to human health. The Bruckner lab is currently focused on volatile organic chemicals (VOCs) and pesticides. High lifetime doses of VOCs cause cancer in mice and rats, but it is unclear whether low environmental exposures pose a cancer risk to humans. Animal studies are being conducted to determine the effectiveness of detoxification presystemic elimination and other protective mechanisms against trace-level exposures. Studies are also conducted to learn whether drug-chemical interactions are of consequence under these conditions. Work is underway to develop physiologically-based pharmacokinetic models for predicting risks of pyrethroid pesticides to children’s health. Grants from the EPA, DOE and CDC support these activities.
Dr. Cummings’ laboratory studies molecular mechanisms involved in cell death, with a particular emphasis on the role of lipids. His team is interested in cell death induced by anti-cancer agents and environmental oxidants. Previous work demonstrated roles of phospholipase A2 (PLA2) in apoptosis and necrosis in numerous cell types. The laboratory uses lipidomic approaches, such as two-dimensional, high performance, thin-layer chromatography in tandem with electrospray ionization mass spectrometry (2D-HP-TLC-ESI-MS), to identify lipids altered in prostate cancer cells and kidney cells exposed to anti-cancer agents. Recent work has also used lipidomics to determine how lipid-based nanoparticles are degraded by PLA2 in cancer cells. They hope to use these data to design and track novel nanoparticulate drug carriers and understand their mechanisms of action.
The Cummings laboratory also studies the molecular mechanisms of cell death induced by water disinfection byproducts (DBPs) such as bromate, which are environmental oxidants. Recent studies show that this class of compounds causes kidney cell death by DNA-dependent and independent mechanisms, and that mixtures of these compounds can induce either apoptosis or necrosis. Current studies are focused on epigenetic changes induced in kidney cells after chronic exposure to low levels of DBPs.
I am interested in studying the interaction of drugs with multiple-drug resistance transporters and drug-metabolizing UDP-glucuronosyltransferases. These proteins play major roles in cancer resistance, in neurological diseases (e.g. Alzheimer’s disease and Parkinson’s) and in mitigating the effects of environmental pollutants. Using human proteins isolated from genetically engineered yeast or bacteria, one goal is to develop structural biology tools to rapidly and accurately predict the effects of drugs and toxins before they end up in people. These tools will allow us to design next generation drugs that are more effective and have fewer side effects than current medications. Another goal is to develop advanced NMR and computational methods to probe the effects of drugs and toxins in whole cells. These techniques will allow us to probe the complex interplay between transporters, receptors and enzymes during drug and metabolite processing. In addition to these research goals, I am developing creative and novel teaching methods to train students of different skill levels in my laboratory. Achieving these research and teaching goals will not only advance medicine and improve drug therapies, but will prepare students well for industry or academic careers in the 21stcentury.