Ute Schwarz
Affiliations
Scientist, Division of Children’s Health and Therapeutics, Children’s Health Research Institute
Scientist, Division of Clinical Pharmacology, Department of Medicine, Schulich School of Medicine & Dentistry, Western University
How my research helps children
My work impacts children who have undergone cardiac surgery, and have to be treated with a blood thinner called warfarin. Warfarin (also known under the brand names Coumadin) is found to be effective for preventing thrombosis and embolism in many disorders by decreasing the ability of blood to clot (coagulation). It is essential to monitor warfarin therapy through frequent blood testing to ensure an adequate yet safe dose is taken. Dosage guidelines for warfarin, the most commonly used oral blood thinner in children, are extrapolated from recommendations for adults, which is not an optimal approach, given the profound age-related differences in blood coagulation. My research has helped to identify certain inherited (genetic) variations that influence warfarin response. In collaboration with Dr. Ralf Rauch, Department of Paediatrics at the Children’s Hospital of Western Ontario, we aim to identify determinants of warfarin therapy in children to help understand how to better personalize warfarin therapy for children.
Research
Current Research Activities
Dr. Schwarz’s translational research is focused on genetic and environmental factors underlying inter-individual variability in drug level and response.
Topics of interest include the pharmacogenetics of clinically relevant drug-metabolizing enzymes such as cytochrome P450 (CYP) 2C9, CYP2D6, TPMT (thiopurine methyl transferase), and vitamin K epoxide reductase (VKORC1) as well as the drug transporters P-glycoprotein and OATP1B3 (Organic anion transporting polypeptide 1B3). Her research further includes the study of mechanisms underlying drug-drug and herb-drug interactions.
Future Research Plans
Dr. Schwarz is collaborating with Dr. Ralf Rauch, Associate Professor, Department of Pediatrics at the Children’s Hospital of Western Ontario, to investigate environmental and genetic factors that determine warfarin therapy in children. She is also starting a collaboration with Dr. David Knoppert, Assistant Professor, Department of Medicine, Division of Clinical Pharmacology, and Adjunct Professor, Department of Paediatrics at Western University, in a study that aims to elucidate the relationship between methadone plasma level and genetic factors and the severity / occurrence of the neonatal abstinence syndrome (NAS) in newborns whose mothers took methadone during pregnancy.
Awards & Grants
Awards & Grants
Western Graduate Research Scholarship in Pharmacology and Toxicology – Awarded by The University of Western Ontario
Presidential Trainee Award, - Awarded by American Society for Clinical Pharmacology and Therapeutics (ASCPT), ASCPT Annual Meeting, Orlando, Florida, March 2005
Funding in support of “Personalized Medicine and Optimal Warfarin Anticoagulant Therapy in Ontario” - Awarded by the Ministry of Health of Ontario
Recent Publications
Publications
Human skeletal muscle drug transporters determine local exposure and toxicity of statins
Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG. Circ Res. 2010 Feb 5;106(2):297-306
Prolonged neutropenia after irinotecan-based chemotherapy in a child with polymorphisms of UGT1A1 and SLCO1B1 Sakaguchi S, Garcia-Bournissen F, Kim R, Schwarz UI, Nathan PC, Ito S.
Arch Dis Child. 2009 Dec;94(12):981-2
Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy Li C, Schwarz UI, Ritchie MD, Roden DM, Stein CM, Kurnik D Blood. 2009 Apr 23;113(17):3925-30.
A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose Cooper GM, Johnson JA, Langaee TY, Feng H, Stanaway IB, Schwarz UI, Ritchie MD, Stein CM, Roden DM, Smith JD, Veenstra DL, Rettie AE, Rieder MJ. Blood. 2008 Aug 15;112(4):1022-7
Breast cancer resistance protein (ABCG2) and drug disposition: intestinal expression, polymorphisms and sulfasalazine as an in vivo probe. Urquhart BL, Ware JA, Tirona RG, Ho RH, Leake BF, Schwarz UI, Zaher H, Palandra J, Gregor JC, Dresser GK, Kim RB Pharmacogenet Genomics. 2008 May;18(5):439-48
Genetic determinants of response to warfarin during initial anticoagulation. Schwarz UI, Ritchie MD, Bradford Y, Li C, Dudek SM, Frye-Anderson A, Kim RB, Roden DM, Stein CM N Engl J Med. 2008 Mar 6;358(10):999-1008
Effect of drug transporter genotypes on pravastatin disposition in European- and African-American participants. Ho RH, Choi L, Lee W, Mayo G, Schwarz UI, Tirona RG, Bailey DG, Michael Stein C, Kim RB. Pharmacogenet Genomics. 2007 Aug;17(8):647-56
Induction of intestinal P-glycoprotein by St John's wort reduces the oral bioavailability of talinolol
Schwarz UI, Hanso H, Oertel R, Miehlke S, Kuhlisch E, Glaeser H, Hitzl M, Dresser GK, Kim RB, Kirch W Clin Pharmacol Ther. 2007 May;81(5):669-78
Intestinal drug transporter expression and the impact of grapefruit juice in humans
Glaeser H, Bailey DG, Dresser GK, Gregor JC, Schwarz UI, McGrath JS, Jolicoeur E, Lee W, Leake BF, Tirona RG, Kim RB Clin Pharmacol Ther. 2007 Mar;81(3):362-70.
Impact of citrus soft drinks relative to grapefruit juice on ciclosporin disposition. Schwarz UI, Johnston PE, Bailey DG, Kim RB, Mayo G, Milstone A. Br J Clin Pharmacol. 2006 Oct;62(4):485-91
Contact
Contact
Phone: 519-685-8500 x 32101
Email: uschwarz [at] uwo [dot] ca
Website: http://www.uwoclinpharm.ca/
(Please note: CHRI is not responsible for the content of any external sites - links will open in new window)