Research activities
Research Areas of Focus:
The research programs focus on drug metabolizing enzymes and its regulation, drug transporters, placental and mammary gland drug transport and metabolism, and reproductive toxicology teratology.
Shinya Ito
Head - Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children (SickKids), University of Toronto.
Dr. Ito's research has focused on Clinical Pharmacology, Drug Transport and Kinetics, and Human Milk.
1. Research Endeavours
a) Breastfeeding pharmacology. This research focus is closely tied with clinical activities in the Motherisk program in collaboration with Dr. Koren. Studies include prospective cohort studies on drug safety during lactation. With many new medications introduced in the market, or about to be introduced in the market, clinical data on safety and information on drug concentration in milk provide previous evidence for rationale therapeutics. In addition, the scope of this program has recently been expanded to economic impact of maternal drug therapy during breastfeeding. Dr. Ito's research group is especially interested in antidepressant therapy.
b) Transport of xenobiotics. Funded mainly by CIHR, this basic research program has investigated various aspects of drug transporters such as P-glycoprotein and organic cation transporters. Current work focuses on drug transfer mechanisms of the mammary gland and its organic cation transporters such as OCTN1, and OCTN2. The ultimate goal is to reveal localization of these transporters in the polarized membrane structures of lactating mammary gland.
c) Effects of milk on development of detoxification mechanisms. The Ontogeny of drug metabolizing enzymes and transporters in the intestine and the liver of the infant remains obscure. This research program funded by CIHR has just begun to explore influences of human milk and its alternatives (i.e., formula) on development of cytochrome P450 enzymes and major drug transporters such as MDR1 P-glycoprotein, MRP2, and PEPT1. In order to elucidate their respective regulatory mechanisms, and to identify responsible compounds in milk, we are using reporter assay for aryl-hydrocarbon receptor (AhR) and SXR/PXR activation. This research is being carried out in collaboration with Drs. P. Harper, H. Yeger, D. O'Connor at SickKids, and Dr. Loddernel at UC Davies.
Gideon Koren
Head and Founder of the Motherisk Program, Professor of Pediatrics, Pharmacology, Pharmacy, Medicine and Medical Genetics, The University of Toronto, Senior Scientist, The Research Institute, The Hospital for Sick Children.
Koren's research focused on:
Pediatric pharmacology: The disposition and effects of drugs on the developing organism with a special interest in the very low birth weight infant and in pediatric cancer chemotherapy. This work involves both basic and clinical studies and aims at tailoring a rational drug schedule for the developing infant and child.
Renal handling of drugs: Application of various in vitro and in vivo methods to study the handling of drugs by the kidney on a molecular and physiological level. Included are: clearance studies; binding studies to the brush border and antiluminal membranes; the multiple indicator injection technique; tissue culture studies. Currently work funded by the CIHR focuses on the renal handling of digoxin by the tubular cell and is being done in collaboration with Dr. M. Silverman, University of Toronto.
Perinatal Toxicology: This research program investigates the adverse effects of drugs and chemicals in the perinatal period. There is a special interest on the teratogenic and developmental effects of drugs and chemicals. Dr. Koren planned and currently directs the "Motherisk" program for antenatal counselling of drug/chemical exposure. This is the first such program in North America and is a prospective project, which assesses both exposed mothers and their offspring. Currently, there is a special focus on the developmental effect of intrauterine exposure to cocaine and carbon monoxide.