Interindividual variation in drug response has long been a hindrance to obtaining effective and safe drug therapy. Differences in a patient’s response to drugs can lead to severe drug toxicity in some or loss of drug efficacy in others. These unexpected responses not only lead to suboptimal patient care but also result in an increased burden to overall health care costs.
In the Personalized Medicine Laboratory, our research is aimed at better understanding the molecular determinants of interindividual variation in drug response. This is accomplished through a variety of research focuses, including assessing pharmacogenetic and pharmacokinetic differences, and studying molecular mechanisms of drug transport and metabolism pathways in the intestine, liver, kidney and pancreas. Our research utilizes a variety of molecular, biochemical, and genetic methods in cellular and animal models coupled with human studies. We use state of the art techniques, such as next-generation sequencing and liquid chromatography-tandem mass spectrometry, to discover new genetic polymorphisms and measure drug levels that may contribute to patient variation in drug response. The results of our research can then be used to help predict adverse drug reactions as well as determine the right dose of medications required for optimal benefit based on an individual’s genetic makeup.
To date, our group has identified a number of genetic polymorphisms in the genes affecting how drugs are cleared from the body, and have used such information to create personalized drug therapies for cancer, vascular disease, and adverse drug reaction prevention. To date, we have used our personalized medicine approach to tailor drug therapies for over 3000 patients.
Currently, our laboratory has a variety of drug transporter research underway. There are several projects studying the involvement of organic anion transporting polypeptides (OATPs) in the cellular uptake of a number of endogenous compounds and clinically relevant drugs. Research areas of interest include elucidating the role of OATPs in pancreatic islet cell function as well as in the progression and chemosensitivity of pancreatic cancer. In addition, we are researching the role of OATP2B1 in promoting oral drug absorption in the intestine and elimination in the liver and the role of NTCP on the disposition of commonly prescribed statin drugs used for cholesterol management. We also have studies focused on understanding altered drug disposition in patients with non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in developed countries.
The Personalized Medicine Research Laboratory consists of a large multidisciplinary team led by three principal investigators and supported by PhD scientists, graduate students, post-doctoral fellows, research associates, technicians, physicians, pharmacists, residents, nurses and coordinators. To learn more about the research of our principal investigators, Dr. Richard Kim, Dr. Rommel Tirona, and Dr. Ute Schwarz, please click on their respective links in Research Opportunities.