The Iversen, Marcus and Annalora laboratories collaboratively focus on the common theme of how chemicals in the environment interact with nuclear hormone receptors (NHRs) and cytochrome P450 enzymes (CYPs) to regulate the activity and metabolism of both xenobiotics and endogenous substrates.   We are interested improving personalized approaches to medicine by clarifying how a patient’s personal history and genetic background shape or “color” their individual response to a drug. 

NSFsummaryFig1Outstanding Question:  How Do Your Genetics and Personal History Interact to Alter Gene Expression Patterns that Promote Disease Susceptibility?

Another innovative aspect of our work revolves around the development of novel small molecule probes for probing DNA/RNA damage, and highly-selective, RNA-based chemical entities designed that can selectively modulate the cellular function of both NHRs (e.g. the vitamin D receptor or VDR) and CYPs (e.g. CYP3A5) that contribute to the metabolism of endo-xenobiotics and pharmaceuticals.  We are focused on understanding how environmental exposures alter discrete, biochemical processes in target organs, such as the kidney, and how these changes promote endocrine disruption, epigenetic modifications to the genome, and the onset of disease.

Outstanding Question:  Can Antisense Therapeutics Be Used to Redirect Human Metabolism to Improve Therapeutic Tolerance and Outcomes?

Another emerging area of research in our group is focused on how the subcellular production radical oxygen species (ROS) linked to stress and chemical exposures can alter the structure, function and stability of RNA molecules.  Collectively, these approaches are being utilized to investigate how an individual’s polymorphic gene status for CYPs and NHRs can help predict their susceptibility to an adverse drug event or disease, by changing their sensitivity to external stressors, aging or related diseases.   

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