Research
The p53-MDM2 pathway in cancer biology and therapy
Our group is primarily interested in how tumour suppressor and oncogene pathways become de-regulated in cancer cells and how an understanding of these processes can be translated into novel strategies for cancer therapy. We focus particularly on the p53/MDM2 pathway and closely-associated pathways, but have broader interests in cancer cell metabolism, cell cycle regulation, apoptosis, the un-folded protein response, senescence and radiation responses. In addition we have substantial translational interests focusing on head and neck cancers, renal cell carcinoma and on colorectal cancers.
Tumour heterogeneity in HPV+ve and HPV -ve head and neck cancers
Tumour heterogeneity is a likely contributor to treatment failure in many cancers. To analyse this in patient samples, we have performed NGS of exomes (WES) of multiple biopsies from individual patients (HPV+ and -ve) using an illumina platform to determine the mutational spectrum and form this infer the sequence of molecular events in each individual patient.
Cancer cell metabolism - p53 as a determinant of metabolic profile
In head and neck and in renal cancer cells we are studying the role and function of the p53 tumour suppressor in determining metabolic profiles; for example the levels of glycolysis, oxidative phosphorylation and also production of ROS and radiation sensitivity (particularly relevant for head and neck). The objective is to identify potential therapeutic strategies based upon an understanding of the cellular dependence on different metabolic pathways.
Research groups
Research grants
Bench Fees for Moneerah Alshammari (201424129)
ROYAL EMBASSY OF SAUDI ARABIA CULTURAL BUREAU IN LONDON (UK)
October 2019 - September 2023
Targeting p53 and FBP1 in ccRCC
MERSEY KIDNEY FIRST (UK)
August 2017 - June 2021
Real-world modelling of the molecular oncology of human papillomavirus-positive head and neck cancer using primary cell culture
THE OTORHINOLARYNGOLOGICAL RESEARCH SOCIETY (UK)
January 2015 - December 2015
Bench fees for Ahoud Alotibi
PRINCE SATTAM BIN ABDULAZIZ UNIVERSITY (SAUDI ARABIA)
September 2016 - August 2020
Bench Fees for Mr Okoturo
LAGOS STATE UNIVERSITY (NIGERIA)
October 2016 - September 2019
Real time in vivo imaging of p53 activity: A novel pre-clinical application
CANCER RESEARCH UK (UK)
October 2011 - September 2012
MDM2 up-regulation promotes poor outcome in renal cell cancer: identifying the targets of MDM2.
MERSEY KIDNEY FIRST (UK)
October 2005 - September 2008
Regulation of MDM2 activity by MTBP.
NORTH WEST CANCER RESEARCH FUND
November 2002 - November 2005
Research into the investigation of the role of MTBP in Cancer (A0331CF).
ROYAL SOCIETY (CHARITABLE)
January 2006 - January 2009
Multi-user cell culture laboratories for Cell Imaging and Stem Cell Research.
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
October 2002 - October 2003
Retroviral Gene Therapy for Pancreatic Cancer.
ROYAL COLLEGE OF SURGEONS OF ENGLAND(UK)
September 2002 - August 2004
Development of a retroviral delivery system for a novel tumour suppressor gene.
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
April 2002 - March 2004
Studies of a novel tumour suppressor molecule MTBP using transgenic technology.
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
May 2001 - April 2003
Cellular biology of the gastrointestinal tract and pancreas in health and disease.
MEDICAL RESEARCH COUNCIL
January 2005 - December 2009
Complex regulation of p53 activity by MDM2, MDMX and MTBP.
NORTH WEST CANCER RESEARCH FUND
October 2005 - October 2008
Development of Dual apoptosis/cell cycle arrest p53 response reporter mouse strain.
CANCER RESEARCH UK (UK)
October 2007 - September 2011
Evaluating the potential of drugs that target heat shock proteins in highly invasive renal cell carcinoma cells
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST CHARITABLE FUNDS (UK)
April 2009 - December 2012
Elucidation and Investigation of the p53 and MDM2 interactomes in Renal Cell Carcinoma
MERSEY KIDNEY FIRST (UK)
January 2008 - September 2013
In vivo investigation of the p53-MDM2 auto-regulatory feedback loop
NORTH WEST CANCER RESEARCH FUND, NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)
October 2011 - March 2014
Cell cycle regulation by MDM2: A combined proteomic and molecular investigation.
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
June 2003 - June 2006
In vivo and in vitro investigation of MTBP: an essential gene and regulator of p53/MDM2
CANCER RESEARCH UK (UK)
July 2007 - March 2011
Multidisciplinary.
HAMPSON TRUST
November 2002 - November 2003
Regulation of the p53 pathway in colorectal cancer.
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
March 2006 - February 2008
Investigating renal cell carriers
MERSEY KIDNEY FIRST (UK)
August 2003 - July 2005
Functional investigation of the interaction of MDM2 with the DNA repair and replication machinery in vitro and in vivo.
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL
June 2001 - June 2004
Functional investigation of novel biomarkers in head and neck cancers
CANCER RESEARCH UK (UK)
September 2011 - August 2013
Regulation of p53 and MDM2 by MTBP.
CANCER RESEARCH UK (UK)
November 2005 - April 2009
Functional analysis of a novel growth regulatory protein. MDM2 Binding Protein 104kD (MDM2-BP) that binds to MDM2 and induces a G1 arrest in the cell cycle that is suppressed by MDM2.
NORTH WEST CANCER RESEARCH FUND
March 2001 - March 2004
A progression model of renal cell cancer: identification of new prognostic and therapeutic targets by DNA microarray analysis.
MERSEY KIDNEY FIRST (UK)
October 2005 - September 2007
Tumour evolution in renal cell carcinoma: developing a novel cell culture model to investigate the role of p53 and MDM2.
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
May 2004 - April 2006
Phenotypic analysis of the MTBP knockout mouse and investigation of the role of MTBP in the p53/MDM2 pathway.
NORTH WEST CANCER RESEARCH FUND
March 2004 - March 2007
MTBP in cancer: A one year pilot study of a candidate tumour suppressor.
NORTH WEST CANCER RESEARCH FUND
April 2003 - April 2004
Research collaborations
Carlos Rubbi
p53 biology
Carlos is a key member of the p53-MDM2 research team.