Cancer kinomics: Kinome-wide analysis of drug-resistance mechanisms in human cancers

Lead Research Organisation: University of Liverpool
Department Name: Institute of Integrative Biology

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/R502339/1 30/09/2017 30/08/2022
1961582 Studentship MR/R502339/1 30/09/2017 30/03/2021 Emma Fairweather
 
Description UGA Franklin college 
Organisation University of Georgia
Country United States 
Sector Academic/University 
PI Contribution Previous work between the Eyers (UoL) and Kannan (UoG) labs has led to the publication of eight research papers, which have fundamentally advanced our understanding of how kinases are regulated. I wish to examine how, and why, drug resistance occurs in tyrosine kinases. This will be achieved by using multidisciplinary approaches that combine skills and techniques from both labs in the broad areas of enzymology, protein biochemistry, computational and structural bioinformatics.
Collaborator Contribution By using state-of-the-art computational methods at the University of Georgia, I am investigating how point mutations in ABL and EGFR directly influence the conformation of the proteins, including how they transition from active to inactive states, and how resistant mutations perturb inhibitor binding
Impact The specific research I propose to pursue in Kannan's lab at UoG involves characterizing effects of mutations found in the ABL and EGFR tyrosine kinases associated with patient drug relapse. This will allow us to understand how these mutations directly influence the structure of these kinases, and the binding and efficacy of FDA-approved drugs for the treatment of chronic myeloid leukaemia (CML) and non-small cell lung cancer (NSCLC).
Start Year 2018