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Research Interests:
Dr. Krasowski's basic research focuses on the regulation of xenobiotic (such as prescription drugs) and endogenous compound metabolism by orphan nuclear hormone receptors such as the pregnane X receptor. There are two major areas of research. The first is to determine the structural determinants of ligand selectivity differences between PXRs from different species using a combination of molecular modeling and functional analysis. The second is to translate novel in vitro findings into hepatocyte models in collaboration with Stephen Strom and the Liver
Biology group.
On the clinical side, Dr. Krasowski directs the Toxicology and Therapeutic Drug Monitoring (TDM) laboratories within the Division of Clinical Chemistry. A major focus over the next several years will be to develop a Clinical Pharmacogenomics service that interfaces with the Toxicology/TDM laboratories. A second area of clinical focus is to develop inductively-coupled plasma mass spectrometry (ICP-MS) to provide state-of-the-art testing for heavy metals and trace metal nutrients.
Selected Publications:
View Dr. Krasowski's publications on PubMed.
Reschly EJ, Krasowski MD. Evolution and function of the NR1I nuclear hormone receptor subfamily (VDR, PXR, and CAR) with respect to metabolism of xenobiotics and endogenous compounds. Curr Drug Metab in press.
Krasowski MD, Yasuda K, Hagey LR, Schuetz EG. Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors). Nuclear Receptor 2005;3:2.
Thompson EE, Kuttab-Boulos H, Krasowski MD, Di Rienzo A. Functional constraints in the constitutive androstane receptor inferred from human sequence variation and cross-species comparisons. Hum Genomics. 2005;2(3):168-178.
Krasowski MD, Yasuda K, Hagey LR, Schuetz EG. Evolution of the pregnane x receptor: adaptation to cross-species differences in biliary bile salts. Mol Endocrinol. 2005 Jul;19(7):1720-39. Epub 2005 Feb 17.
Krasowski MD, Hong X, Hopfinger AJ, Harrison NL. 4D-QSAR analysis of a set of propofol analogues: mapping binding sites for an anesthetic phenol on the GABA(A) receptor. J Med Chem. 2002 Jul 18;45(15):3210-21.
Krasowski MD, Nishikawa K, Nikolaeva N, Lin A, Harrison NL. Methionine 286 in transmembrane domain 3 of the GABAA receptor beta subunit controls a binding cavity for propofol and other alkylphenol general anesthetics. Neuropharmacology. 2001 Dec;41(8):952-64.
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