Geoffrey Liu

Picture of Dr. Geoffrey Liu

Associate Professor

M.D. University of Toronto

Ontario Cancer Institute / Princess Margaret Hospital
610 University Avenue, Room 7-124
Toronto, Ontario M5G 2M9

Phone: (416) 946-4501 x3428
Lab Phone: (416) 946-4501 x3428
Email Dr. Geoffrey Liu

 

Pharmacogenomic Epidemiology

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

 

List of Key Publications:

Link to Pubmed Publications
  • Liu G, Gurubhagavatula S, Zhou W, Wang Z, Yeap BY, Asomaning K, Su L, Heist R, Lynch TJ, Christiani DC. Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib. Pharmacogenomics J. 2007

  • Liu G, Zhou W, Yeap BY, Su L, Wain JC, Poneros JM, Nishioka NS, Lynch TJ, Christiani DC. XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk. Carcinogenesis. 2007 Jun;28(6):1254-8.

  • Cescon DW, Bradbury PA, Asomaning K, Zhai R, Hopkins J, Kulke MH, Su L, Heist RS, Wain JC, Lynch TJ, Christisani DC, Liu G. p53, MDM2, and CCND1 polymorphisms in esophageal cancer prognosis. Clin Cancer Res. 2009 May 1;15(9):3103-9.

  • Bradbury P, Hopkins J, Singh S, Tse D, Kulke MH, Heist RS, Asomaning K, Marshall AL, Su L, Nishioka NS, Lynch TJ, Wain JC, Christiani DC, Liu G. Matrix Metalloproteinase polymorphisms and risk of esophageal cancer. Carcinogenesis. 2009 May;30(5):793-8.

  • Savas S, Geraci J, Jurisica I, Liu G. A comprehensive catalogue of functional genetic variations from the EGFR pathway: protein-protein interaction analysis reveals novel genes and polymorphisms important for cancer research. Int J Cancer 2009 Sep 15;125(6):1257-65.

  • Bradbury PA, Kulke MH, Heist RS, Pintilie M, Zhou W, Marshall AL, Asomaning K, Su L, Nishioka NS, Shepherd FA, Lynch TJ, Wain JC, Christiani DC, Liu G. DNA Repair Gene Polymorphisms Predict Clinical Outcome. Pharmacogenet Genomics. 2009 Aug;19(8):613-25.

  • Cheung WY, Zhai R, Kulke M, Heist RS, Asomaning K, Ma C, Wang Z, Su L, Lanuti M, Tanabe KK, Christiani DC, Liu G. Epidermal Growth Factor (EGF) A61G Gene Polymorphism, Gastroesophageal Reflux Disease (GERD), and Esophageal Adenocarcinoma (EAC) Risk. Carcinogenesis. 2009 Aug;30(8):1363-7.

  • Meyer F, Samson E, Douville P, Duchesne P, Liu G, Bairati I. Serum Prognostic Markers in Head and Neck Cancer. Clin Cancer Res. 2010 Feb 1;16(3):1008-15.

  • Wheatley-Price P, Yang B, Patel D, Ma C, Xu W, Anraku M, O’Sullivan B, Leighl N, Ron Feld, Cho BCJ, de Perrot M, Liu G. Mesothelin as a marker of response in malignant pleural mesothelioma. J Clin Oncol 2010 Jul 10;28(20):3316-22. Epub 2010 May 24.

  • G Liu, S Gramling, D Munoz, DX Cheng, AK Azad, M Mirshams, Z Chen, W Xu, H Roberts, FA Shepherd, MS Tsao, D Reisman. Two movel BRM insertion promoter sequence variants are associated with loss of BRM expression and lung cancer risk. Oncogene. 2011 Jul 21;30(29):3295-304.

  • C Rogers, S Gramling, G Liu, D Reisman. Pharmacologic reversal of epigenetic silencing of the anticancer protein BRM: a novel targeted treatment strategy. Oncogene. 2011 Jul 21;30(29):3289-94.

  • Lin X, Cai T, Wu MC, Zhou Q, Liu G, Christiani DC, Lin X. Kernel machine SNP-set analysis for censored survival outcomes in genome-wide association studies. Genet Epidemiol. 2011 Nov;35(7):620-31

  • Azad AK, Bairati I, Samson E, Cheng D, Mirshams M, Savas S, Waldron J, Wang C, Goldstein D, Xu W, Meyer F, Liu G. Validation of Genetic Sequence Variants as Prognostic Factors in Early Stage Head and Neck Squamous Cell Cancer Survival. Clin Cancer Res. 2011 Nov 10. [Epub ahead of print]

  • Meyer F, Fortin A, Wang CS, Liu G, Bairati I. Predictors of Severe Acute and Late Toxicities in Patients with Localized Head and Neck Cancer Treated with Radiation Therapy. Int J Radiat Oncol Biol Phys. 2011 Jun 1. [Epub ahead of print]

  • Azad AK, Bairati I, Samson E, Cheng D, Cheng L, Mirshams M, Savas S, Waldron J, Goldstein D, Xu W, Meyer F, Liu G. Genetic Sequence Variants and the Development of Secondary Primary Cancers in Patients with Head and Neck Cancers. Cancer. 2011 Aug 25. doi: 10.1002/cncr.26446.

  • Liu G, Cheng D, Ding K, Le Maitre A., Liu N., Patel D, Chen Z, Seymour L, Shepherd FA, Tsao MS. Pharmacogenetic Analysis of BR.21, a Placebo-controlled Randomized Phase III Clinical Trial of Erlotinib in Advanced Non-Small Cell Lung Cancer. J Thoracic Oncol accepted, November, 2011

 

Graduate Students:

  • Lorin Dodbiba
  • Jennifer Teichman