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.
People |
ORCID iD |
Margaret Ashcroft (Primary Supervisor) | |
Alhasan Al-Habib (Student) |
Publications
Al-Habib Alhasan
(2022)
Investigating the role of mitochondria in the hypoxia response using in vitro and in vivo models
Al-Habib H
(2021)
CHCHD4 (MIA40) and the mitochondrial disulfide relay system.
in Biochemical Society transactions
Thomas LW
(2019)
CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain.
in Cancer & metabolism
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N013433/1 | 30/09/2016 | 29/04/2026 | |||
1941443 | Studentship | MR/N013433/1 | 30/09/2017 | 31/01/2022 | Alhasan Al-Habib |
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 |