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Miss Amira Hussain

Research project: Development of a LC-MS/MS method for the simultaneous quantification of metabolic reaction products catalysed by cytochrome P450 enzymes in rat hepatic microsomes and human hepatic progenitor cells

Abstract

Biotransformation in the liver is accomplished by two classes of enzymes; namely phase I and phase II biotransformation enzymes. Cytochome P450s (CYPs) are pivotal phase I mono-oxygenase enzymes involved in the synthesis and degradation of endogenous steroid hormones, vitamins, and fatty acid derivatives, but also in the transformation of xenobiotics such as drugs and environmental chemicals into more hydrophilic molecules, thus facilitating their excretion (1). Of this CYP family, CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4 are considered to be the major isoforms responsible for the metabolism of the majority of marketed drugs in humans. Inhibition or induction of CYPs by drugs can cause drug-drug interactions, altering their effectiveness or resulting in toxic interactions (2). In addition, CYP isozyme levels can be affected by other factors such as age and disease (3).

The purpose of this proposed CYP induction in vitro test method is to evaluate the potential of a test chemical (see Table 1) to induce CYP mediated via PXR/CAR (CYP3A4, CYP2B6) and the Ah-135 receptor (CYP1A2) in rat and human based cells, thus establishing differences. The selection of these three CYP isoforms, which are recommended by the EMA and FDA Guidelines, is based on the fact that in humans they are involved in the biotransformation of a wide variety of endogenous and exogenous chemicals and that they are target CYPs for classical model inducers: CYP1A2 for dioxins and PAHs, CYP2B6 for phenobarbital and CYP3A4 for rifampicin.

  • Research degree: PhD
  • Title of project: Development of a LC-MS/MS method for the simultaneous quantification of metabolic reaction products catalysed by cytochrome P450 enzymes in rat hepatic microsomes and human hepatic progenitor cells
  • Research supervisor: Dr James Barker

Biography

Before my masters degree in biological sciences in UK, I have worked as a full time job as a chemistry and science teacher in a school, and I was also used to demonstrate in the lab during my M.Phil (back home). During my masters degree at Royal Holloway, University of London, I have brushed up my skills and gained some knowledge about proteins/peptides and drugs used for the detection and treatment of breast cancer.

Currently, I am doing PhD at Kingston University, London in analytical chemistry.

Areas of research interest

  • Analytical chemistry
  • Drug Drug interactions
  • Inhibitory effect of drugs on Phase 1 and Phase 2 enzyme activity (CYP450, and UGTs) using LC-MS/MS techniques
  • Affinity peptidomics and lateral flow assay
  • Protein characterization

Qualifications

  • PhD in Analytical Chemistry (continue), Kingston University, London.
  • Masters by Research in Biological Sciences, Royal Holloway, University of London.
  • Postgraduate Diploma in strategic management and leadership, London College of International Business Studies.
  • Postgraduate Diploma in Biotechnology, University of Bedfordshire, UK.
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