A5010372937- Pharmacogenetics and Drug Metabolism
- Plant biochemistry and biosynthesis
- Drug Transport and Resistance Mechanisms
- Computational Drug Discovery Methods
- Lipid metabolism and biosynthesis
- Chemical Reactions and Isotopes
- Hormonal and reproductive studies
- Analytical Chemistry and Chromatography
- Hormonal Regulation and Hypertension
- Microbial Metabolic Engineering and Bioproduction
- HIV/AIDS drug development and treatment
- Antibiotics Pharmacokinetics and Efficacy
- Microbial Natural Products and Biosynthesis
- Pharmaceutical studies and practices
- Insect and Pesticide Research
- Eicosanoids and Hypertension Pharmacology
- Drug-Induced Hepatotoxicity and Protection
- Antibiotic Resistance in Bacteria
- Receptor Mechanisms and Signaling
- Birth, Development, and Health
- Pneumocystis jirovecii pneumonia detection and treatment
- Environmental Chemistry and Analysis
- Berberine and alkaloids research
- Cancer therapeutics and mechanisms
- Plant Surface Properties and Treatments
University of Montana
2021-2024
University of Colorado Anschutz Medical Campus
2021-2024
University of Colorado System
2023
University of Colorado Denver
2021-2022
University of Kansas Medical Center
2017-2018
University of Washington
2017
University of Kansas
2017
Sekisui XenoTech (United States)
2014-2015
Institut de Biologie Moléculaire des Plantes
2007-2012
Université de Strasbourg
2012
The jasmonate hormonal pathway regulates important defensive and developmental processes in plants. Jasmonoyl-isoleucine (JA-Ile) has been identified as a specific ligand binding the COI1-JAZ co-receptor to relieve repression of responses. Two JA-Ile derivatives, 12OH-JA-Ile 12COOH-JA-Ile, accumulate wounded Arabidopsis leaves COI1- JAR1-dependent manner reflect catabolic turnover hormone. Here we report biochemical genetic characterization two wound-inducible cytochromes P450, CYP94C1...
Liver injury due to acetaminophen (APAP) overdose is the major cause of acute liver failure in United States. While treatment with N-acetylcysteine current standard care for APAP overdose, anecdotal evidence suggests that administration 4-methylpyrazole (4MP) may be beneficial clinic. The objective study was examine protective effect 4MP and its mechanism action. Male C57BL/6J mice were co-treated 300 mg/kg 50 4MP. severe induced by at 6 h as indicated elevated plasma alanine...
An approach based on an in silico analysis predicted that CYP77A4, a cytochrome P450 so far has no identified function, might be fatty acid-metabolizing enzyme. CYP77A4 was heterologously expressed Saccharomyces cerevisiae strain (WAT11) engineered for expression. Lauric acid (C(12:0)) converted into mixture of hydroxylauric acids when incubated with microsomes from yeast expressing CYP77A4. A variety physiological C(18) were tested as potential substrates. Oleic (cis-Delta(9)C(18:1))...
The metabolism of testosterone to 6<i>β</i>-hydroxytestosterone (6<i>β</i>-OH-T) is a commonly used assay evaluate human CYP3A enzyme activities. However, previous reports have indicated that CYP3A7 also produces 2<i>α</i>-hydroxytestosterone (2<i>α</i>-OH-T) and 2<i>α</i>-OH-T/6<i>β</i>-OH-T ratio may be unique endogenous biomarker the activity enzyme. Until now, full metabolite kinetic profile for hydroxylation by has not been fully examined. To this end, we performed complete analysis...
We cloned and characterized CYP709C1, a new plant cytochrome P450 belonging to the family, that so far has no identified function except for clustering with fatty acid metabolizing clade of enzymes. showed here CYP709C1 is capable hydroxylating acids at omega-1 omega-2 positions. This work was performed after recoding heterologous expression full-length cDNA isolated from wheat library in an engineered yeast strain. Investigation on substrate specificity indicates metabolizes different...
A fatty‐acid‐metabolizing enzyme from Arabidopsis thaliana , CYP94C1, belonging to the cytochrome P450 family was cloned and characterized. CYP94C1 heterologously expressed in a Saccharomyces cerevisiae strain (WAT11) engineered for expression. When recombinant yeast microsomes were incubated with lauric acid (C12:0) 15 min, one major metabolite formed. The product purified identified by GC/MS as 12‐hydroxylauric acid. Longer incubation (40 min) led formation of an additional dodecadioic...
Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role a posttranslational modification proteins called O-GlcNAcylation, where O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes single β-D-N-acetylglucosamine (O-GlcNAc) moiety, pathogenesis APAP-induced injury. Hepatocyte-specific OGT knockout mice (OGT KO), which reduced wild-type (WT) controls were treated with 300 mg/kg APAP development injury was studied over time course from 0 to 24 h....
Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen that highly prevalent in individuals with cystic fibrosis (CF). A major problem treating CF patients infected P. the development of antibiotic resistance. Therefore, identification novel drug targets utmost urgency. The genome contains four putative cytochrome P450 enzymes (CYPs) unknown function have never before been characterized. Analogous to some CYPs from Mycobacterium tuberculosis, these may be important for growth...
Berberine is an isoquinoline alkaloid plant extract that widely available as a dietary supplement in the United States and has demonstrated efficacy treatment of type 2 diabetes mellitus dyslipidemia. Because its increased use purported pharmacological properties, potential variations product quality could pose barrier to berberine's safety effectiveness clinical practice. Thus, this study evaluated potency supplements containing berberine U.S. commercial market. Fifteen unique were...
The CYP3A7 enzyme accounts for ~50% of the total CYP content in fetal and neonatal livers is predominant involved xenobiotic metabolism. Additionally, it a key player healthy birth outcomes through oxidation dehydroepiandrosterone (DHEA) DHEA-S (sulfate). amount other hepatic CYP3A isoforms, CYP3A4 CYP3A5, expressed neonates low, but highly variable, therefore activity individual isoforms difficult to differentiate due their functional similarities. Consequently, better understanding...
Prophylactic antiretroviral therapy (ART) in HIV infected pregnant mothers and their newborns can dramatically reduce mother-to-child viral transmission seroconversion the neonate. The ritonavir-boosted lopinavir regimen, known as Kaletra, has been associated with premature birth transient adrenal insufficiency newborns, accompanied by increases plasma dehydroepiandrosterone 3-sulfate (DHEA-S). In fetus neonates, cytochrome P450 CYP3A7 is responsible for metabolism of DHEA-S into 16α-hydroxy...
CYP3A7 is a member of the cytochrome P450 (CYP) 3A enzyme sub-family that expressed in fetus and neonate. In addition to its role metabolizing retinoic acid endogenous steroid dehydroepiandrosterone sulfate (DHEA-S), it also has critical function drug metabolism disposition during first few weeks life. Despite this, generally ignored preclinical testing new candidates. This increases risk for drug-drug interactions (DDI) toxicities occurring Therefore, screening candidates inhibition...
Heme oxygenases (HO) catalyze the oxidative cleavage of heme to generate biliverdin, CO, and free iron. In humans, oxygenase-1 (hHO-1) is overexpressed in tumor tissues, where it helps protect cancer cells from anticancer agents, while HOs fungal pathogens, such as Candida albicans, function primary means iron acquisition. Thus, HO can be considered a potential therapeutic target for certain diseases. this study, we have examined equilibrium binding three isocyanides, isopropyl, n-butyl,...
Human fetal cytochrome P450 3A7 (CYP3A7) is involved in both xenobiotic metabolism and the estriol biosynthetic pathway. Although much understood about 3A4 its role adult drug metabolism, CYP3A7 poorly characterized terms of interactions with categories substrates. Herein, a crystallizable mutated form was saturated primary endogenous substrate dehydroepiandrosterone 3-sulfate (DHEA-S) to yield 2.6 Å X-ray structure revealing unexpected capacity simultaneously bind four copies DHEA-S. Two...
Idiosyncratic drug reactions (IDRs) in their most deleterious form can lead to serious medical complications and potentially fatal events. Nevirapine (NVP), still widely used developing countries for combinatorial antiretroviral prophylactic therapies against HIV infection, represents a prototypical example of IDRs causing severe skin rashes hepatotoxicity. Complex metabolic pathways accompanied by production multiple reactive metabolites often complicate our understanding IDR's origin....