Goal – Identify key regulatory pathways and proteins that mediate damage related to hyper-phosphorylated tau in human brain tissue.
Outcome – Identification of significant targets in multiple key pathways including those related to metabolism, calcium regulation, synaptic processes, protein mis-folding and inflammation.
Collaborators - University of Eastern Finland
Goal – Establish the mechanism of action of two orally available, brain-penetrant small molecule inhibitors of casein kinase 1 delta that improved cognition in a rodent tauopathy model.
Outcome – Confirmation that many tau phosphorylation sites are reduced by drug treatment, as well as significant regulation of pathways demonstrated to involved in phospho-tau dependent disease mechanisms.
Goal – Analyse the context in which melanoma-derived cell lines exploit MEK and PI3K signalling to overcome BRAF V600E resistance.
Outcome – Identification of a number of common effects of combination therapy irrespective of the second target as well as specific effects dependant on targeting either MEK or PI3K.
Collaborators – Moffitt Cancer Centre, Tampa, Florida
Goal – Establish common mechanisms of actions between preclinical mice treated with CK1D inhibitors and post mortem human AD brain tissue.
Outcome – With many pathways, proteins and phosphorylation sites quantified in both datasets several translational biomarkers were identified.
Collaborators University of Eastern Finland
Goal – Identify pharmacodynamic biomarkers in AD cerebrospinal fluid.
Outcome – Common data outputs from SysQuant® and TMTcalibrator™ enabled the identification of pharmacodynamic biomarker candidates by comparing datasets from human clinical tissue, drug-treated animal tissues and human AD CSF samples.
Collaborators University of Eastern Finland, Kuopio University Hospital, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital and Institute of Neurology, University College London
Goal Profile signalling pathways driving pancreatic ductal adenocarcinomas
Outcome – Analysis of 32 cases shows pathways controlling how cells interact with each other and the tumor stroma are consistently affected in all patients. However, greater heterogeneity was seen in the activity of several key drug targets highlighting the need for personalised treatments for each patient.
Collaborators King’s College Hospital
Goal – Use SysQuant® to explore inter-tumoral differences in active cellular processes driving individual liver tumors with a focus on targets of therapy including Sorafenib.
Outcome – Maps of pathway activity showed low level of Raf activity in most tumors suggesting Sorafenib will seldom be an effective treatment. Other kinase targets showed broader activity profiles and represent better targets for HCC treatment.
Collaborators – Professor Nigel Heaton Liver, Renal, Urology, Transplant, Gastro/Gastro Intestinal Surgery Clinical Academic Group