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What is this project about?

The liver is involved in over 75% of the drug metabolism process that determines drug safety and efficacy and hence is widely used in the pharmaceutical industry to predict these factors during drug discovery and development. Interindividual and interpopulation differences in drug response make it difficult to extrapolate the safety and efficacy of medicines studied in one population to another population. Drugs under development and those in current use have been evaluated for safety and efficacy in the European population, leaving the African population comparatively understudied. To address this gap, AiBST has established ALTBio, which has collected liver tissue from 70 volunteers. To support drug metabolism studies, this tissue has been processed to subcellular fractions, and the materials are being further characterized with respect to the activities of the major drug metabolizing enzymes (CYP450s, UGTs). In this proposal, we plan to characterize the tissue with respect to variation of genes coding for proteins important for drug absorption, distribution, metabolism and excretion. This will be done using an ADMEseq Next Generation Sequencing panel of 340 genes comprising phase I and II enzymes, drug transporters and regulator/modifier genes within their entire coding regions, adjacent intron regions and 5′ and 3′UTR regions.

Funder

ICGEB

PI & Team Members

Collen Masimirembwa (PI)

Darline Dize (Postdoctoral Fellow)

Zedias Chikwambi (Co-Investigator)

Collaborators

None

Period
2024

Pharmacogenomics in an Africa Liver Tissue Biorepository

Pharmacogenomic characterization of liver tissue from a cohort of donors of African ancestry as a tool in the discovery and development of medicines that is inclusive of African population genomic diversity
Project Media

Publications

None

The Aim

The current study aims to determine the genomic variation of a panel of 340 pharmacogenes in 70 liver tissues from African donors using next-generation sequencing.

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Objectives
  1. Sequence DNA from the liver tissue donors for a panel of 340 pharmacogenes

  2. Correlate genomic variation with activities of drug metabolizingenzymes in the liver microsomes and primary hepatocytes.

  3. Predict the functional effects of novel genetic variants likely to be uncovered in the donors

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