Clinical Proteomics and Biomarker Discovery Doug Ward SCIRA

Clinical Proteomics and Biomarker Discovery Doug Ward SCIRA Research Fellow (Translational Medicine)

A biomarker is a measurable parameter that reports on a particular pathological state (not a symptom). Underlie tests for: - Screening, diagnosis or prognosis - Predicting and monitoring response (personalised medicine) Desperate need for better biomarkers in many (all? ) disease areas. Many existing biomarkers are proteins that ‘leak’ from diseased tissue e. g. cardiac troponin, PSA. Modern proteomic methods are ideally suited to identify new clinically useful biomarkers.

Proteomics – MDS (Birmingham) Maxis Electrospray ultra-high resolution Q-TOF <<1 ppm accuracy 24 spectra per second Amazon ETD Electrospray ion trap with ETD and PTR PTMs Top-down sequencing SRM Ultraflextreme MALDI-TOF/TOF <1 ppm accuracy Imaging Profiling Peptides/proteins

Biofluid profiling: Also……. Tissue proteomics, other ‘omics’, biomarker validation, panels of biomarkers

Research Plan Optimise peptidomic and proteomic methods on AWM-funded mass spectrometers Validate candidate cancer biomarkers Develop hepcidin research and liver markers Proteomic biomarker analysis of Clinical Trial samples and other Science City disease areas To combine. . . clinical resources, advanced ‘omic’ analyses and advanced data analysis to develop clinically useful biomarkers.

Biomarker Research is truly inter-disciplinary and inter-institutional…. . Identify unmet clinical need (clinicians and epidemiologists) Technology/Instruments Assay development (scientists) Commercial development Biomarker Validation Sample analysis (instrumentation, scientists) Data storage and mining (bioinformaticians) Multi-site Clinical Trials (statisticians, nurses, administrators) Intellectual Property protection Biomarker Discovery Study design (statisticians and bioinformaticians) Appropriate clinical material (clinicians, biobanking and Clinical Trials) Biomarker Application Manufacture, marketing and distribution