Arthur G. Zupko Institute for Systems Pharmacology and Pharmacogenomics
Arthur G. Zupko’s Institute of Systems Pharmacology and Pharmacogenomics is housed in a newly built and equipped laboratory that currently performs metabolomics research. Mass spectrometry is employed to conduct metabolomics investigations into the causation, prevention and treatment of human diseases through the discovery and quantitation of biomarkers. Such studies generally lead to an enhanced understanding of the pathobiology of disease. We have a number of active projects related to various liver diseases, leukemia, lung cancer and multiple sclerosis, together with disease prevention through dietary manipulation with collaborators from US and European universities and from the US National Cancer Institute, NIH. We plan to increase our outreach to other diseases using our expertise in metabolism and the application of mass spectrometry-based metabolomics. The laboratory has now started to train pharmacy students within its research program.
This paper is an advance in our understanding of liver cirrhosis, a disease that kills over 1.3 million persons per annum (35,000 deaths in the US; 9th leading cause of death). Understanding the severity of cirrhosis is key to treatment. So-called decompensated cirrhosis is an end-stage disease for which the only intervention is liver transplantation, which is offered to less than 10% of patients due to the shortage of donor livers.
The findings that fetal bile acids, normally absent in adults, reach increasingly high levels in plasma as the disease progresses adds not only an important biomarker for evaluation of the stage of cirrhosis but also provides mechanistic insights that parallel inborn errors of bile acid metabolism in neonates and young children.
Oncometabolites are produced by cancer cells and assist the cancer to proliferate and progress. Oncometabolites occur as a result of mutated enzymes in the tumor tissue or due to hypoxia. These processes result in either the abnormal buildup of a normal metabolite or the accumulation of an unusual metabolite. Definition of the metabolic changes that occur due to these processes has been accomplished using metabolomics, which mainly uses mass spectrometry platforms to define the content of small metabolites that occur in cells, tissues, organs and organisms. The four classical oncometabolites are fumarate, succinate, (2R)-hydroxyglutarate and (2S)-hydroxyglutarate, which operate by inhibiting 2-oxoglutarate-dependent enzyme reactions that principally regulate gene expression and response to hypoxia. Metabolomics has also revealed several putative oncometabolites that include lactate, kynurenine, methylglyoxal, sarcosine, glycine, hypotaurine and (2R,3S)-dihydroxybutanoate. Metabolomics will continue to be critical for understanding the metabolic rewiring involving oncometabolite production that underpins many cancer phenotypes.
Jeff Idle, Ph.D., FRSC, FRSB, FBPhS
Director and Endowed Professor, Arthur G. Zupko’s Systems Pharmacology and Pharmacogenomics
Dr. Jeffrey R. Idle received a BSc in Applied Chemistry from The Hatfield Polytechnic (now University of Hertfordshire) in 1972 after completing industrial training in the development labs of Geigy Ltd (now Novartis) in Manchester in 1971. After a further period of industrial training in the pharmaceutical development labs of Wander Ltd (now Novartis) in Kings Langley in 1972, he received a BSc (First Class Hons) in Medicinal Chemistry from The Hatfield Polytechnic in 1973. He then studied under Professor R. Tecwyn Williams, FRS, the founding father of drug metabolism, receiving his PhD from the University of London in 1976. He has held the positions of Lecturer in Biochemistry, Lecturer in Biochemical Pharmacology, Wellcome Trust Senior Lecturer, and Reader in Pharmacogenetics at St. Mary’s Hospital Medical School, London. He was the co-discoverer of the first genetic polymorphism of cytochrome P450 (CYP2D6) in 1977. Professor Idle is a Fellow of the Royal Society of Chemistry, the Royal Society of Biology, and the British Pharmacological Society. His research history spans drug metabolism, pharmacogenetics, metabolomics, and lipidomics, particularly as applied to medicine.
Diren Beyoğlu, Ph.D., CBiol, MRSB
Associate Director and Associate Professor, Arthur G. Zupko’s Systems Pharmacology and Pharmacogenomics
Dr. Diren Beyoğlu received a BSc in Pharmacy from Marmara University in 2000. She received an MSc in Pharmaceutical Toxicology in 2002 and a PhD in Pharmaceutical Toxicology in 2006, both from Marmara University in Turkey. She has held the positions of Research Assistant, Lecturer, and Assistant Professor in Pharmaceutical Toxicology at Marmara University. Her research in Turkey concerned determination of chemical contaminants in foodstuffs. She trained in Molecular Pharmacogenetics with Professor Ondřej Slanař, Director, Institute of Pharmacology, Charles University in Prague and in mass spectrometry-based metabolomics in the laboratory of Dr. Frank J. Gonzalez, National Cancer Institute, NIH. In 2018, she joined LIU as Associate Director and Associate Professor, Arthur G. Zupko’s Systems Pharmacology and Pharmacogenomics. Her research has primarily focused on clinical applications of metabolomics and lipidomics in the areas of hepatology and oncology.