Ute I. Schwarz
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Associate Professor Office: University Hospital, C9-100C Post-Doctoral Fellowship – Vanderbilt University in Nashville, USA |
Academic Journey
Dr. Schwarz received her medical degree at the Technical University Dresden, Germany in 1995, and subsequently her accreditation in Clinical Pharmacology in 2003. She completed a postdoctoral fellowship in the Division of Clinical Pharmacology at Vanderbilt University in Nashville, USA (1999-2000) which focused on the pharmacogenetics and drug interactions involving drug metabolizing enzymes and drug transporters. In 2004, Dr. Schwarz joined the Division of Clinical Pharmacology, Department of Medicine, at Vanderbilt University as a Research Instructor. Subsequently, she completed her Ph.D. graduate training in Pharmacology & Toxicology at the University of Western Ontario (2007-2012) with the thesis title “Intestinal and hepatic drug transporters and their role in the disposition of lipid lowering drugs”. Dr. Schwarz was appointed as Assistant Professor at the University of Western Ontario in 2013.
Why Science?
Working as a scientist provides the unique ability to discover new insights and gain a better understanding of complex problems. As a clinical pharmacologist, I am able to pursue translational research, which comprises cell-based models, animal experiments as well as studies in healthy individuals or patients. Such research may facilitate clinical implementation of new discoveries that increase efficacy or reduce undesired effects of drug therapies.
Research Goals
Within the Personalized Medicine Program, Dr. Schwarz pursues studies evaluating factors that influence variation in drug exposure, therapeutic response, and toxicity in adult and pediatric patient populations with focus on drug metabolizing enzymes and drug transporters.
Specific Research Interests
1. Interpatient Variability to DOACs
Dr. Schwarz’s research is focused on better understanding interpatient variability in blood exposure and adverse effects of direct oral anticoagulants (also DOACs), a new class of medications prescribed in patients with irregular heartbeat to prevent strokes.
2. Pharmacogenetic Predictors of Drug Response in Pediatric Oncology
Dr. Schwarz’s collaborative research in the area of pediatric oncology aims to discover genetic factors that can better predict therapeutic and/or adverse drug responses of anti-cancer medications. Her research examines how genetic factors and blood drug level may help guide dosing of the anticancer medication mercaptopurine in children with acute lymphoblastic leukemia (or ALL), a common childhood cancer, in order to prevent severe bone marrow toxicity. A second study evaluates if genetic markers and blood exposure of the chemotherapeutic drug methotrexate predict renal toxicity in children with leukemia. Another area of interest relates to how genetic factors may help optimize the prescribing of anti-nausea medications for children undergoing cancer therapy.
3. Understanding the Potential Role of OATP Uptake Transporters in Statin-Induced Impairment of Beta Cell Function
Statins are substrates of uptake transporters belonging to the organic anion transporting polypeptide family (OATPs) and are commonly used to treat hypercholesterolemia. While well tolerated in most patients, statins have been recently associated with an increased risk in new diabetes mellitus. A current project applies cell-based and transgenic mouse models as well as clinical studies to investigate underlying mechanisms of statin-induced impaired beta cell function involving drug transport. Preliminary results suggest expression of OATPs in human pancreatic islets, reduced insulin secretion and increased mitochondrial toxicity in cells treated with statins.
4. Development of a Next-Generation Gene Sequencing (NGS) Strategy
Dr. Schwarz has been leading the development and validation of a next-generation gene sequencing (NGS) strategytargeting exomes of 100 drug metabolizing enzymes, transporters, and some drug targets to enable the discovery of novelgenetic predictors underlying variable therapeutic response or drug toxicity.
Undergraduate Teaching:
PHARM 4660A – Human Toxicology (course manager)
PHARM 4350A – Clinical Pharmacology
PHYS/PHARM 3000E – Labs
Advice to Students
Do not be discouraged if an experiment does not work the first time; patients and perseverance are key requirements to succeed. And even so frustrating, making mistakes can provide a great opportunity to learn.
| 2007-2012 |
Western Graduate Research Scholarship in Pharmacology and Toxicology
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| March 2005 |
Presidential Trainee Award, American Society for Clinical Pharmacology and Therapeutics (ASCPT)
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| March 2003 |
Teaching Award, Medical Faculty Carl Gustav Carus, Technical University Dresden
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Highlighted Publications
Gulilat M, Keller D, Linton B, Pananos DA, Lizotte D, Dresser GK, Alfonsi J, Tirona RG, Kim RB, and Schwarz UI. Drug interactions and pharmacogenetic factors contribute to variation in apixaban concentration in atrial fibrillation patients in routine care. Journal of Thrombosis and Thrombolysis 49:294-303 (2020).
Gulilat M, Lamb T, Teft WA, Wang J, Dron JS, Robinson JF, Tirona JG, Hegele RA, Kim RB, and Schwarz UI. Targeted next generation sequencing as a tool for precision medicine. BMC Medical Genomics 12: 81 (2019).
Kim M, Deacon P, Tirona, RG, Kim RB, Pin CL, Meyer zu Schwabedissen HE, Wang R, Schwarz UI.Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of the adult human pancreas. Histochem Cell Biol 148:345-357 (2017).
Vasudev K, Choi YH, Ross N, Kim RB, Schwarz UI. Genetic determinants of clozapine-induced metabolic side effects. Can J Psychiatry 62:138-149 (2017).
Schwarz UI, Ritchie MD, Bradford Y, Dudek SM, Frye-Anderson A, Kim RB, Roden DM, Stein CM. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 358: 999-1008 (2008).
