Research
Metastatic Spread of Cancer in Model Systems
Model systems, particularly these relating to breast cancer have been used for identification of Metastasis-Inducing Proteins (MIPs), their target molecules, their mechanism of action and their inhibitors. These MIPs include S100A4, S100P, Anterior Gradient 2 (AGR2) and osteopontin with others now flowing through our pipeline. For example we have shown that S100A4/P interacts with the cytoskeleton (myosin IIA, tubulin) so as to promote reduction in adhesion molecules/increases in cell migration and increases in proteases/increases in cell invasion. The model systems used include S100P-inducible cell cultures for cell migration/invasion in vitro, and S100A4 genetically-engineered Drosophila and MIP-transfected cell-implanted syngeneic rats for study of metastasis in vivo. These MIPs are then tested on clinical specimens to ascertain their clinical relevance (see Research Interest 2).
Metastatic Spread of Cancer in Humans
The potential role of our Metastasis-Inducing Proteins (MIPs) in human cancers, particularly breast cancer has been approached using immunohistochemical detection in clinical specimens of normal, benign, malignant and metastatic lesions and relating results in malignant tumours and metastases to pathological parameters and clinical outcomes using a variety of statistical tests. These MIPs include S100A4, S100P, AGR2, osteopontin, as well as the homologous double strand DNA repair marker, nuclear FANCD2 which is inversely associated with their production. Cancers under study include early and advanced breast cancers, endometrial, prostate, head and neck, colon carcinomas and brain metastases from primary carcinomas in a variety of organs. All 4 of our original MIPs show enhanced expression in malignant tumours and their metastases and a strong correlation with early patient demise in breast cancer has been discovered so far, other results are in the pipeline.
Research grants
Bench Fees Bandar Alenezi
NORTHERN BORDER UNIVERSITY (SAUDI ARABIA)
April 2018 - March 2023
Invasion of brain metastases
ROYAL COLLEGE OF SURGEONS OF ENGLAND(UK)
December 2015 - November 2016
Therapeutic Approach to Metastasis: Chemical conjugation of inhibitors for in vivo targeting of S100 metastasis-inducing protein degradation
CANCER AND POLIO RESEARCH FUND LTD (UK)
May 2017 - October 2018
Morteta Al-Medhtiy - bench fees
REPUBLIC OF IRAQ MINISTRY OF EDUCATION🚩
October 2014 - September 2017
Therapeutic Approach to Metastasis: Preclinical testing of specific inhibitors of the S100 family of Metastasis-Inducing Proteins
CANCER AND POLIO RESEARCH FUND LTD (UK)
April 2015 - April 2017
Role of regulatory molecules in delivery of the mitogenic response by LIF
ROYAL SOCIETY (CHARITABLE)
June 2006 - August 2006
Genetic Changes in a Transgenic Mouse Model of Human Breast Cancer.
CLATTERBRIDGE CANCER RESEARCH
October 1996 - March 2002
Identification of signalling processes involved in stabilisation of Cyclin D1mRNA and its relevance to cell proliferation.
NORTH WEST CANCER RESEARCH FUND
August 2002 - August 2005
Determination of the structure of the complex between S100P and Tubulin and its role in cell migration and metastasis
CANCER AND POLIO RESEARCH FUND LTD (UK)
April 2013 - April 2015
S100A4 protein self-association and metastasis.
NORTH WEST CANCER RESEARCH FUND
May 2004 - December 2007
Growth factors in the developing ureter and potential role in the pathogenesis of congenital urinary obstructions.
CANCER AND POLIO RESEARCH FUND LTD (UK)
January 1999 - November 2013
Structure-Function Relationships in metastasis-inudcing protein AGR2
NORTH WEST CANCER RESEARCH FUND
December 2007 - December 2011
Cancer and Polio Research Laboratory.
CANCER AND POLIO RESEARCH FUND LTD (UK)
January 1993 - December 2023
Evaluation of Metastasis-inducing Proteins as Biomarkers of Patient Outcome in Human Cancers
MEDICAL RESEARCH COUNCIL
September 2009 - February 2013
Miss Batool Almarzouq - Bench fees
ROYAL EMBASSY OF SAUDI ARABIA
November 2014 - October 2017
Liverpool Centre of Experimental Cancer Medicine.
CANCER RESEARCH UK (UK)
July 2007 - March 2012
Structural Motifs in S100 Proteins that cause Metastasis
NORTH WEST CANCER RESEARCH FUND
June 2007 - August 2010
The role of Microtubules in S100P - induced cell migration and mestasis
CANCER AND POLIO RESEARCH FUND LTD (UK)
April 2009 - January 2011
To determine whether the metastasis-inducing properties of S100P arise from extracellular or intracellular sources
CANCER AND POLIO RESEARCH FUND LTD (UK)
August 2007 - July 2009
The genetics of metastases
CANCER RESEARCH & GENETICS UK
November 2014 - June 2016
The role of metastasis inducing proteins and telomerase in Endometrial cancer and in endometrial cancer stem cells; Implications for diagnosis, prognosis and treatment
WELLBEING OF WOMEN (UK)
January 2013 - January 2014
Cancer and Polio Research Fund Central Facility for Molecular Oncology.
CANCER AND POLIO RESEARCH FUND LTD (UK)
April 2001 - July 2009
Relevance of Transcriptional Regulators of Osteopontin Gene Expression to Breast Cancer Metastasis.
CANCER AND POLIO RESEARCH FUND LTD (UK)
January 2000 - August 2008
To investigate the role of the identified regulators of cell fate (RCF) and metastasis inducing proteins (MIP) in endometrial stem/progenitor cells (SPC) in establishing endometriosis.
WELLBEING OF WOMEN
October 2009 - July 2013
The Role of Interactions between Estrogen Receptors and Tcf-related Molecules on Osteopontin Gene Expression and Breast Cancer Metastasis.
CANCER AND POLIO RESEARCH FUND LTD (UK)
September 2002 - August 2008
Relevance of the Reciprocal Regulation of Osteopontin Gene Expression by Estrogen Receptor and Tcf-4 to Breast Cancer Metastasis.
NORTH WEST CANCER RESEARCH FUND
January 2001 - September 2004
Evaluation of the therapeutic role of microRNAs in S-100 induced breast cancer metastasis
CANCER AND POLIO RESEARCH FUND LTD (UK)
April 2011 - March 2013
Investigation of a novel mechanism for the mitogenic action of Leukemia Inhibitory Factor and its possible role in malignant transformation
NORTH WEST CANCER RESEARCH FUND
September 2005 - August 2008
Identification of signalling molecules in developmental pathways of the abnormal urinary tract and the role of its vascularisation.
CANCER AND POLIO RESEARCH FUND LTD (UK)
January 2004 - June 2005
Study visit.
ROYAL SOCIETY (CHARITABLE)
August 2002 - January 2003
Investigation of local brain invasion by cerebral metastases and implications for clinical management
MEDICAL RESEARCH COUNCIL
May 2014 - April 2016