The laboratory of Geoffrey Liu is also known as the Applied Molecular Profiling Pharmacogenetic Epidemiology Laboratory (AMP-PEL). AMP-PEL focuses on biomarker research associated with risk, screening, treatment and prevention outcomes. This translational research includes predictive biomarkers, pharmacogenomics, and radiogenomics. All research focuses on translational research with direct clinical implications to improve current treatment and prevention strategies through individualization of patient therapies or prevention strategies. AMP-PEL has active translational, clinic-epidemiologic, and health services research components.
Pharmacogenomic Epidemiology (PGE) is the application of molecular epidemiologic methods to pharmacogenetics, which has provided new opportunities to evaluate rigorously the role of genomic factors in cancer treatment outcomes and toxicity. When large clinical trials involving the drugs of interest are available, secondary analysis of such trials is the preferred method of studying pharmacogenetics. However, there are many instances, such as in rare tumours or when trying to evaluate pharmacogenetics in standard chemotherapy or radiotherapy treatments, where clinical trials care not available to answer important pharmacogenetic questions. Under these circumstances, the role of carefully planned prospective observational studies becomes instrumental to answer both pharmacogenetic and cancer prognosis questions. The quality of results obtainable from these studies is highly dependent on the methods used to recruit patients, to obtain and process samples, to accurately measure genetic markers, to determine accurate phenotypes and outcomes, and to perform appropriate statistical analysis. In addition, pharmacogenomic functional assays and testing are an important component. Therefore, PGE results from these high quality observational studies and clinical trials, the goal of much of AMPPEL's efforts, have strong potential to impact on patient risk stratification, and in the choice of appropriate therapies.
AMP-PEL has performed and continues to perform PGE evaluations in clinical trials and observational studies, using archival tissue, fresh tissue, blood and other surrogate tissues. The methodologic approaches used include: candidate-based analyses, pharmacokinetic (PK) and pharmacodynamic (PD) pathway analyses, genome-wide association studies (GWAS) and post-GWAS analyses (includes methods development), Next Generation Sequencing (Whole Exome, Whole Genome Sequencing). Sites of disease for these analyses includes: lung, head and neck, breast, gastro-esophageal, hepatobiliary, pancreatic, ovarian, testicular, Mesothelioma, and thymoma.
Gastro-esophageal Cancer Primary Xenograft Program: AMPPEL’s pharmacogenomic research also developed and utilizes mouse xenografts carrying primary human gastro-esophageal tumours (obtained during biopsy and resection). These xenografts have been treated with conventional chemotherapy, radiation, and chemoradiation since 2009. These xenografts are also treated with novel targeted agents (with or without radiation). Thus, this research involves the evaluation of pharmacogenomic and radiogenomic changes during treatment of these xenografts, characterization of these xenografts for various oncogenic and tumour suppressor gene pathways, and evaluation of molecular targeted agents in these xenografts. This set of primary human cancer derived xenografts is a unique resource, given the paucity of esophageal adenocarcinoma cell lines.
Functional Analysis of Polymorphisms: The Liu laboratory is applying molecular biologic tools to complement ongoing PGE studies, including COMET assays (for DNA repair capacity), luciferase promoter and binding assays, using cancer cell lines and cell lines derived from healthy individuals to study the role of the functional consequences of these polymorphisms.
Radiogenomics: Given the importance of radiation and chemoradiation in many of AMPPEL’s primary disease sites (head and neck cancer, gastroesophageal cancer, lung cancer, pancreatic cancer), research expanded to evaluate the role of genomics and genetics of normal tissue toxicity after radiation. Along with colleagues in Quebec, AMPPEL has completed the first ever genome-wide association study (GWAS) of radiogenetics in head and neck cancer patients treated solely with radiation (CCSRI funded).
Lung Cancer Early Detection and Prevention Biomarker Program: The specific focus of this research is to identify biomarkers that can refine the selection for CT screening, and biomarkers that identify patients for specific interventions. Dr. Liu has coordinated the collection of biospecimens, spirometry, epidemiologic and clinical data coordination for the PMH Lusi Wong CT Screening Early Detection Program. Since 2010, Dr. Liu has been working with Dr. Reisman (U Florida) on the Brahma-HDAC pathway polymorphisms as potential biomarkers of risk and primary prevention intervention.
Other Areas of Research: Mesothelioma Biomarker Research, Knowledge Translation of Pharmacogenomics; Classical and Molecular Epidemiology