Dr Michael Cross

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.

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.

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.