Photo of Em P Philip Rudland

Em P Philip Rudland MA, PhD, FRCPath, FIBiol, FRSA

Chair Biochemistry, Cell and Systems Biology

    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