Drug Action, Metabolism and Kinetics Training Grant

项目来源

美国卫生和人类服务部基金(HHS)

项目主持人

KODURI, SAILAJA

项目受资助机构

UNIVERSITY OF WASHINGTON

立项年度

2019

立项时间

未公开

项目编号

2T32GM007750-41

项目级别

国家级

研究期限

未知 / 未知

受资助金额

496563.00美元

学科

Health Disparities; Minority Health;

学科代码

未公开

基金类别

TRAINING, INSTITUTIONAL

关键词

未公开

参与者

ATKINS, WILLIAM M

参与机构

NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

项目标书摘要:Project Summary This pre-doctoral Pharmacological Sciences Training Program (PSTP) is a cross-disciplinary program that represents a merger of research training opportunities in the Schools of Medicine (Pharmacology) and Pharmacy (Medicinal Chemistry and Pharmaceutics) at the University of Washington. The rationale for this program is that it is essential for providing in-depth training in several inter-related disciplines that are central to current and future research related to the discovery, validation and development of new drug targets and new chemical entities that will improve global health. This focus distinguishes training provided by the PSTP from other pre-doctoral training grants available at UW. The primary objective of the PSTP is to develop scientists, equipped with the necessary background in the biological and chemical sciences and training in the application of modern tools of research and instrumental techniques, to undertake and direct fundamental research related to drug action, metabolism and pharmacokinetics. Trainees follow tracks that emphasize training in four broadly defined areas: (I) cellular and molecular pharmacology, (II) structure and drug/vaccine design, (III) drug metabolism, (IV) pharmacokinetics, drug transport and delivery, which exist in the departments of Pharmacology, Medicinal Chemistry and Pharmaceutics. Didactic components involve individualized, highly multidisciplinary programs of coursework and seminars that are centered on the biological and chemical sciences. Additional program elements include a PSTP-specific journal club, a 'career' day that brings scientists from varied 'nontraditional careers' to speak with trainees, industry mentors and internships, and recently added emphasis on rigor and reproducibility. The program brings together 34 well-funded faculty members whose research emphasizes training in mechanisms and regulation of cell signaling, neuropharmacology, structural analysis of pharmacologically relevant protein-ligand interactions, mechanistic and bio- analytical aspects of drug metabolism and toxicology, pharmacogenetics, pharmacokinetics/dynamics and drug transporter function and regulation. Under-represented and disadvantaged students, who are actively recruited through a number of faculty activities, currently represent ~33% of the training cohort. In this competitive renewal of the Pharmacological Sciences National Research Service Award program, support is requested for 13 pre-doctoral trainees per year. The selection of trainees will be on a competitive basis from the pool of students in years 1-3, who are committed to research in one of the aforementioned areas.

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  • 2.Analysis of vitamin A and retinoids in biological matrices

    • 关键词:
    • SMALL-MOLECULE INHIBITORS; IONIZATION BEHAVIOR; ACID SYNTHESIS; IN-VITRO; STABILITY; QUANTIFICATION; CYP26A1; SERUM; METABOLISM; CAROTENOIDS
    • Czuba, Lindsay C.;Zhong, Guo;Yabut, King C.;Isoherranen, Nina
    • 《RETINOID SIGNALING PATHWAYS》
    • 2020年
    • 会议

    Vitamin A signaling pathways are predominantly driven by the cellular concentrations of all-trans-retinoic acid (atRA), as the main mechanism of retinoid signaling is via activation of retinoic acid receptors. atRA concentrations are in turn controlled by the storage of vitamin A and enzymatic processes that synthesize and clear atRA. This has resulted in the need for robust and highly specific analytical methods to accurately quantify retinoids in diverse biological matrices. Tissue-specific differences in both the quantity of retinoids and background matrix interferences can confound the quantification of retinoids, and the bioanalysis requires high performance instrumentation, such as liquid chromatography mass-spectrometry (LC-MS). Successful bioanalysis of retinoids is further complicated by the innate structural instability of retinoids and their relatively high lipophilicity. Further, in vitro experiments with retinoids require attention to experimental design and interpretation to account for the instability of retinoids due to isomerization and degradation, sequential metabolism to numerous structurally similar metabolites, and substrate depletion during experiments. In addition, in vitro biological activity is often confounded by residual presence of retinoids in common biological reagents such as cell culture media. This chapter identifies common biological and analytical complexities in retinoid bioanalysis in diverse biological matrices, and in the use of retinoids in cell culture and metabolic incubations. In addition, this chapter highlights best practices for the successful detection and quantification of the vitamin A metabolome in a wide range of biological matrices.

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