About Drug Disposition, Dynamics, Pharmacology & Pharmacogenomics
Understanding the time course of drug in the body is a critical element in the development of dosage regimens (how much drug to give how often and by what route). The development and application of mathematical models to describe this process and its interface with drug action is a critical step in the development of new drugs, as well as improving the use of existing agents.
In addition, understanding the processes by which drugs are absorbed, metabolized and eliminated are key to understanding drug effects after administration. Such knowledge can allow clinicians and scientists to anticipate and manage drug interactions and adverse effects, while maximizing the desired therapeutic effects. Researchers can also use these tools to gain an understanding of the fundamental mechanisms of disease.
Faculty of the Division of Pharmaceutics and Translational Therapeutics are actively engaged in research in this area at the molecular, biochemical, cellular, and whole body level.
Research in Drug Disposition & Dynamics
Dr. Guohua An's research interest include building mechanism-based pharmacokinetic and pharmacodynamic modeling of small molecules (such as tysosine kinase inhibitors) and large molecules (such as Epo), understanding the mechanisms of poor brain penetration and offering novel approaches to overcome it and evaluating the transporter- and enzyme-based herbal-drug interactions.
Our laboratory conducts Translational Pharmacology and basic science research. There are 3 major research areas in the lab, with several projects within each area that range from in vitro biochemistry, to cell culture & rodent models and even human cardiac tissue specimens. The mitochondria is a focal point of the research program. We routinely collaborate with medicinal chemists to study novel lead therapeutic compounds in heart and liver disease. One major effort is directed at targeting mitochondria in cardiomyocytes and fibroblasts to mitigate cardiac complications of diabetes and atrial fibrillation. There is also a basic science component directed towards a greater understanding of the role of mitochondria in cellular energetics and signaling pathways (nuclear cross-talk, paracrine factors, etc). Long-term, this work is expected to lead to novel therapies.
A brief overview of each area and project information can be found on my lab website: https://www.ejandersonlab.com/.
Note: We are collaborating with cardiac surgeons from UIowa Heart & Vascular Center, and elsewhere, to obtain samples of human heart tissue. Most of these samples are atrial tissue which is obtained during routine cardiac surgeries. Tissue is dissected immediately from the patient on the operating table, and either placed straight into our preparatory buffer (for immediate testing) or frozen in liquid N2 and stored in our cryo-repository. Fibroblasts are often cultured from these samples (day of surgery), and these cells are then stored in cryo-vials in our repository. Matching blood samples from each patient (preoperative) are also available. Samples are made available to researchers in academia or industry upon request.
Research Area #1 - Cross-talk between Monoamines and Nutrient Metabolism in the Heart
Research Area #2 - Examining the Role of Reactive Aldehydes in Cardiac Remodeling with Diabetes and Aging
Research Area #3 - Elucidating the Metabolic and Anti-Inflammatory mechanisms of Mitochondrial Prohibitin (PHB)
Dr. Smith's laboratory studies mechanisms of RNA regulation, focusing on spatial and temporal dynamics of RNA expression. A major aim of the laboratory is to identify functional polymorphisms that modulate RNA expression. These polymorphisms are substrate for a number of downstream applications, including genetic association studies in complex genetic disorders and pharmacogenetic analyses, novel drug target identification and validation, and studies on evolutionary selection pressures. The Smith Laboratory also uses transgenic animal models to study fundamental mechanisms of RNA expression and to identify cell type-specific and subcellular RNA expression profiles in central nervous system tissues.