Photo of Dr Michael Cross

Dr Michael Cross

Senior Lecturer Molecular and Clinical Pharmacology

    Research

    The role of cardiac microvascular endothelial cells in drug-induced cardiovascular toxicity

    Drug-induced cardiovascular toxicity is one of the leading causes of adverse reactions in patients leading to drug withdrawal. My research has focused on the potential role of cardiac microvascular endothelial cells in drug-induced cardiac injury. In collaboration with AstraZeneca, we have recently developed a novel multi-cellular 3D cardiac microtissue composed of human stem cell derived cardiomyocytes (hESc-CMs), human cardiac fibroblasts (HCFs) and human cardiac microvascular endothelial cells (HCMECs). This cardiac microtissue allows us to analyse both structural and functional toxicity in vitro in multiple cardiac cell types. By understanding how cardiotoxic cancer drugs, such as doxorubicin and molecular targeted drugs, such as Herceptin, can adversely affect HCMECs we may be able to ameliorate this pharmacologically leading to reduced adverse cardiac effects in cancer patients.

    The role of liver sinusoidal endothelial cells in drug-induced liver injury (DILI)

    Drug-induced liver injury (DILI) is one of the leading causes of drug attrition. In collaboration with Prof. Chris Goldring (Univ of Liverpool) and AstraZeneca we are analysing the role of human liver sinusoidal endothelial cells (HLSECs) in liver function. We have utilized mRNA transcriptomic analysis to determine the unique gene expression in HLSECs compared with other microvascular endothelial cells. We have also developed a multicellular liver microtissue composed of HLSECs, human liver fibroblasts and hepatocytes allowing us to analyse adverse effects of drugs on multiple hepatic cell types. By understanding HLSEC physiology we aim to determine if these cells offer a therapeutic potential to reduce DILI and potentially stimulate liver regeneration.

    The role of ERK5 in melanoma development and tumour angiogenesis

    Melanoma is highly aggressive skin cancer. In collaboration with Prof. Richard Marais (Manchester Cancer Institute) Dr. Cathy Tournier (Univ of Manchester) and Mr Rowan Pritchard-Jones (Whiston Hospital) we are investigating the role of ERK5 in melanoma development and metastatic spread via angiogenesis and lymphangiogenesis. We use a number of in vitro cell models, tumour spheroids and analysis of patient samples to determine how the ERK5 signalling axis is involved in melanoma growth.

    Research Grants

    Bench Fees for Suad Hassan S Alghamdi

    ROYAL EMBASSY OF SAUDI ARABIA CULTURAL BUREAU IN LONDON (UK)

    October 2018 - September 2021

    The role of VEGF signalling and ERK5 activity in vemurafenib resistant melanoma progression

    THE SKIN CANCER RESEARCH FUND (UK)

    October 2016 - September 2019

    Dissecting the immunological, cellular and molecular basis of adverse effects induced by therapeutic antibodies

    ROYAL EMBASSY OF SAUDI ARABIA

    February 2012 - January 2016

    The role of the ERK5 signalling axis in drug-resistant melanoma progression

    NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

    August 2016 - May 2019

    Angiogenesis and melanoma metastasis via lymphatics. Resolving the paradox

    THE SKIN CANCER RESEARCH FUND (UK)

    February 2011 - August 2012

    The role of angiogenesis and lymphangiogenesis in vemurafenib resistant melanoma progression

    NORTH WEST CANCER RESEARCH FUND

    May 2014 - July 2016

    Establishing a 3D spheroid model of melanoma cells to study interaction with vascular and lymphatic endothelial cells.

    SOCIETY OF BIOLOGY (UK)

    June 2012 - July 2012

    Analysis of the role of ERK5 gene expression in a human tumour angiogenesis cell model

    ROYAL EMBASSY OF SAUDI ARABIA

    January 2012 - January 2016

    WELLCOME VIP2 2007/08

    WELLCOME TRUST (UK)

    October 2007 - September 2008

    The role of Phospholipase D in tumour angiogenesis

    CANCER RESEARCH UK (UK)

    July 2010 - June 2011

    CRW Funded MPHIL

    CANCER RESEARCH WALES (UK)

    October 2008 - September 2010

    Validating anti-angiogenic and anti-lymphangiogenic targets as a treatment modality for drug resistant melanoma

    THE SKIN CANCER RESEARCH FUND (UK)

    May 2013 - April 2014

    Analysis of the Molecular and Genetic Interaction Between Human Vascular Smooth Muscle and Endothelial Cells In an In Vitro Blood Vessel Model.

    ROYAL EMBASSY OF SAUDI ARABIA

    March 2012 - February 2013

    The role of the PLC-y, PKC and CA2+ signalling axis in VEGF-medicated angiogenesis.

    NORTH WEST CANCER RESEARCH FUND

    May 2008 - October 2011

    The role and regulation of phospholipase D activation in human endothelial cells

    ROYAL EMBASSY OF SAUDI ARABIA

    October 2010 - September 2014

    Research Collaborations

    Prof. Lena Claesson-Welsh

    External: Uppsalla University

    Analysis of VEGFR-2 mutants in endothelial cells

    Dr. Bettina Wilm

    Internal

    Development of in vitro cardiovascular cell models

    Prof. Dave Fernig

    Internal

    We are collaborating on a project analysing the potential role of a novel dimeric Fc-Neuropilin1 molecule as a VEGFR-2 agonist in endothelial cells.

    Dr. Ashley Martin

    External: The University of Birmingham

    Proteomic analysis of VEGF-stimulated tyrosine phosphorylated proteins in human endothelial cells