Examining processes that affect drug disposition (metabolism and transport) in pediatric patients
In the use of pharmaceutical treatment, what works for one patient may not work for another. There are many factors that can influence treatment efficacy, but an individual’s biology and genetic makeup have a considerable impact. Our laboratory works to understand how these genetic factors impact drug metabolism and transport. Establishing this understanding is key as we explore more effective treatments for children with catastrophic diseases.
The majority of our laboratory’s work focuses on three areas related to processes that affect drug disposition. Our major efforts concentrate on pharmacogenetics, the creation of experimental models, and the study of metabolomics. Each of these areas allows us to deepen our understanding of different genetic mechanisms that can influence drug disposition and treatment efficacy.
Our study of pharmacogenetics allows us to understand the influence of genes on drug metabolism and transport. We are particularly interested in genes that encode proteins that influence drug metabolism, transport, and the regulation of these processes. Our research focuses on the CYP drug metabolism enzymes, particularly the CYP3A family, that helps metabolize half of all clinically administered drugs. In our work, we partner with investigators at other institutions to determine the association of newly identified CYP3A4 and 3A5 genetic variants to disposition of CYP3A substrates in order to better predict the right dose for each patient.
Creating preclinical models
A major effort within our laboratory is the creation of advanced preclinical models to examine metabolism and transport processes and how they may impact a drug’s efficacy. In our development of preclinical models, our goal is to study the influence of drug transporters on drug disposition and predict their role in drug-drug interactions (DDI). Our laboratory develops models to study a variety of environments that may impact drug disposition.
In the examination of small molecules and how they interact with their larger environment, our laboratory seeks to identify endogenous substrates of drug efflux transporters. Our studies use models that lack the drug efflux transporters BCRP, PGP, and MRP4. We conduct metabolomic analysis of fluids (CSF, urine, and plasma) to identify putative substrates so we can better understand the transporter’s overall endogenous functions, identify transporter biomarkers, and predict drug-induced metabolic alterations. Our work in this area will help elucidate how changes in metabolic pools due to transporter inhibition could cause metabolic changes and rewire drug sensitivity indirectly.
Dr. Erin G. Schuetz contributes her extensive research experience to St. Jude’s Department of Pharmacy and Pharmaceutical Sciences. She earned her PhD from the Medical College of Virginia (VCU) and contributed to major discoveries concerning the CYP drug metabolism enzymes. As a Faculty Member at St. Jude, Schuetz leads her lab in the study of processes and genetic variation that impact drug disposition.
A dedicated team of specialists committed to discovering the processes and genetic variations that lead to variation in drug disposition.