Investigating novel hypoxia inducible factor (HIF) regulatory pathways in cancer

Lead Research Organisation: University of Cambridge
Department Name: Medicine

Abstract

Cancer causes one in four of all deaths in the UK (Cancer Research UK) and is a disease of many diseases, each cancer type has a different genetic and biological profile. There is an unmet need for developing new therapeutic interventions that can be used to improve front-line treatments. A unifying feature found in cancers is hypoxia (low oxygen levels) Hypoxia leads to increased activation of hypoxia inducible factors (HIFs). Hypoxia and HIF activation is associated with treatment resistance and poor patient prognosis using front-line treatments (e.g. radiotherapy). While HIF itself is considered a challenging drug target, preventing HIF activation in cancer is an attractive strategy for the development of new anticancer agents. Thus elucidating the cellular processes underlying the regulation of HIF activity and HIF-mediated tumour progression are of particular interest therapeutically. The overall goal of the project will be to characterise novel HIF regulatory genes identified from a genetic screen.

Publications

10 25 50
 
Description OON KHYE BENG CH'HIA TSIO Studentship for Research In Preventative Medicine
Amount £4,000 (GBP)
Organisation University of Cambridge 
Department Downing College, Cambridge
Sector Academic/University
Country United Kingdom
Start 12/2018 
End 12/2019
 
Title High Throughput evaluation of Zebrafish embryo biological endpoints 
Description High Throughput evaluation of Zebrafish embryo hatching in normoxia and hypoxia. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2019 
Provided To Others? No  
Impact Novel biological insight that will contribute to publishable work. 
 
Description Generating HRE-GFP (Hypoxia Response Element) reporter zebrafish using chchd4-targeted zebrafish 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution Generating HRE-GFP (Hypoxia Response Element) reporter zebrafish using chchd4-targeted zebrafish
Collaborator Contribution Provision of HRE-GFP (Hypoxia Response Element) reporter zebrafish
Impact Generating HRE-GFP (Hypoxia Response Element) reporter zebrafish using chchd4-targeted zebrafish
Start Year 2019
 
Description Generating Zebrafish knockout lines for chchd4a and chchd4b 
Organisation University College London
Department Division of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution My team led the project. My role was the genetic analysis, identification and confirmation of all the chchd4-targeted zebrafish lines for my PhD project.
Collaborator Contribution Assistance with the generation (CRISPR) of the chchd4-targeted zebrafish lines. Assistance with maintenance of the lines.
Impact Assistance with the generation (CRISPR) of the chchd4-targeted zebrafish lines.
Start Year 2013
 
Description Maintenance/Breeding of CRISPR chchd4 targeted Zebrafish Lines 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution Genotyping all new generations of fish that were raised to adulthood.
Collaborator Contribution Maintenance and husbandry under our collaborator's PPL (70/8180).
Impact Generation and characterisation of chchd4-targeted zebrafish.
Start Year 2018