The overarching mission of the Experimental Pathology Unit (EPU) is the establishment of a bidirectional approach to biomedical discovery by translating basic science into clinical practice, and utilizing clinical observations to develop novel hypotheses to be tested in the research laboratory, aiming to improve human health by understanding the basis of disease and building bridges between biomedical scientists in the Faculty of Medicine and clinical specialists in the Health Care Services
The EPU strengthens the philosophy of integration and collaboration between members of the Department of Pathology as well as associate members from other departments in the Faculty of Medicine who share common research niches, by optimizing the use of available technology, research platforms, instrumentation, and research applications.
The EPU takes advantage of the uniqueness of the discipline of Pathology, historically based on the gross and microscopic analysis of tissues and currently expanding the knowledge of cell and molecular biology. Pathology constitutes an ideal foundation for linking basic and clinical scientific research with clinical practice and nurturing the formation of multidisciplinary work groups.
The main goal of the EPU is to expand our understanding of all aspects of disease, from gross anatomy to the molecular roots, thus contributing to the betterment of patient diagnoses and treatments while training the next cadre of health professionals and educators. The research program covers a wide variety of pathologies with a special emphasis on high fatality diseases.
The EPU is closely intertwined with the Graduate Studies Program in Pathology that has an integrative and comprehensive focus on organismal biology and pathology while imparting scientific rigor in training our diverse group of students following a team-based mentoring approach.
Gastrointestinal & Liver Pathology Research Laboratory
Director: Dr. Zu-Hua Gao
The laboratory is equipped with facilities for routine histology and immunohistochemistry, imaging, laser microdissection, cell culture, western blotting and other molecular testing.
Current and Future Research Projects
1. Molecular mechanisms of colon cancer progression metastasis
2. Developing new drugs that could inhibit the progression of colon cancer
3. Novel biomarkers for pancreatic adenocarcinoma
4. Molecular mechanisms of primary biliary cirrhosis.
Multiple Sclerosis Pathogenesis Research Laboratory
Director: Dr. David Haegert
Over the past 10 years, Dr. Haegert’s laboratory has focused on alterations in naive T-cell homeostasis in patients with multiple sclerosis (MS). His laboratory found that patients with both relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) have early thymic involution with reduced thymic output of naive T-cells including recent thymic emigrants. More recent work indicates for the first time that early thymic involution leads to a homeostatic peripheral naive T-cell proliferative response. This finding has potential relevance to MS pathogenesis, as homeostatic proliferation is implicated in autoimmunity in experimental animal models and in the development of autoimmunity in humans.
More recent work used whole genome microarray studies to analyze isolated naive CD4 T-cells from patients with secondary progressive MS (SPMS). Unexpectedly, unbiased hierarchical clustering segregated patients with SPMS into two groups, one group, termed SP-1, having a short RRMS duration and one group, termed SP-2, having a long RRMS duration. SP-1 patients upregulated numerous genes involved in immune activation compared to healthy controls and SP-2 patients. Subsequent analysis identified a list of 130 T-cell activation genes that also separated SP-1 patients from healthy controls and SP-2 patients. This gene list was reduced to 3 genes which similarly separated SP-1 from controls and SP-2. The specificity of these 3 genes for SP-1 patients was confirmed at the protein expression level and in T-cell activation experiments. Since SP-1 patients had a significantly shorter RRMS duration that SP-2 patients (mean of 12 vs. 24 years), the 3-gene signature is a possible biomarker (at mRNA and protein express levels) that identifies patients having rapid transition from RRMS to SPMS.
Current and Future Research Projects
Current studies in the laboratory focus on the 3-gene signature as a putative biomarker signature predicting disease progression in patients with progressive MS. This signature is being investigated in two ways. Firstly, the signature is being evaluated by flow cytometry in patients treated with FTY 720 (Gilenya) in order to determine whether expression of this signature on one or more CD4 T-subsets (naive, central memory, effector memory and TEMRA cells) predicts either response to treatment or disease progression or both. Secondly, the signature is being evaluated in patients with progressive MS (both SPMS and PPMS) to determine whether expression of this signature on one or more CD4 T-subsets changes over time and whether increased expression of this signature distinguishes between patients who have rapid vs. slow MS progression. Assessment of MS progression involves collaboration with expert neurologists and neuroradiologists and includes evaluation by clinical parameters, including the Expanded Disability Status Scale or EDSS and MRI parameters that assess atrophy and inflammation within the CNS.
The list of 130 genes having increased expression in naive CD4 T-cells from SP-1 patients includes various genes that were not previously evaluated at either the protein expression or functional level. Some of these molecules will be further evaluated in patients with progressive MS at the mRNA and protein expression levels, both before and after T-cell activation. The long term goal of this work is to develop a convenient biomarker signature that predicts rates of MS progression and potential responses to treatment.
Respiratory Disease Research Laboratory
Director: Dr. Qutayba Hamid
Dr. Qutayba Hamid is an internationally renowned researcher into respiratory disease and has been at the forefront of asthma and chronic obstructive pulmonary disease research for over 20 years. He leads a number research programs on asthma, COPD and airway inflammation at the Meakins-Christie Laboratories of the McGill University Health Centre (MUHC). The Meakins-Christie Laboratories constitute one of the premiere centres for respiratory research on a global scale and serve as an important training ground for graduate students and postdoctoral fellows from all over the world.
Respiratory diseases are a leading cause of mortality in Canada and over 3 million Canadians of all ages have a serious respiratory disease. The top two leading respiratory diseases affecting Canadians are asthma and chronic obstructive pulmonary disease (COPD). Asthma is now the most common of all respiratory diseases in Canada, with about 2.7 million cases and over 750,000 Canadians are believed to be living with COPD. In 2012–2013, respiratory disease cases such as COPD accounted for the highest hospitalization costs at $445 million.
ASTHMA Research Group
The main characteristics of asthma are the presence of respiratory symptoms associated with a variable airflow limitation, airway hyperresponsiveness, and bronchial inflammation and structural changes (remodelling). Dr. Hamid’s research group aims to understand the underlying features of severe asthma disease. The main aim is to describe the inflammation, the remodelling, the corticosteroids resistance and the potential chronic infection in these patients. Clinical research is currently done using a cohort of moderate and severe asthmatics with a long term follow-up. Clinical characterization is done using a wide screening testing to detect concomitant health problems. The inflammation and remodelling features are studied using induced sputum and endobronchial biopsies.
COPD Research Group
Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent disease affecting over 300 million individuals worldwide, for which there is no available cure, representing the fifth leading cause of death. COPD is a chronic and progressive condition characterized by gradual airway obstruction, shortness of breath, cough and sputum production. The inflammation pattern is believed to induce structural cells apoptosis and tissue degradation leading to chronic bronchitis and emphysema. This research group aims to identify and understand the cellular and molecular mechanisms that control apoptosis and inflammation, two signature processes which are impaired in COPD.
Allergic Rhinitis Research Group
Allergic Rhinitis is an important health problem affecting up to 40% of the worldwide population. Its prevalence in the Canadian population is between 10 to 25%. The main symptoms of allergic rhinitis are nasal congestion, runny nose, sneezing and post-nasal drip. Allergic rhinitis has a cellular inflammation pattern characterized by eosinophil, mast cell and CD4+ T cell infiltration. This research group studies the inflammatory process and the effect of various stimulations (allergenic or therapeutic) on nasal mucosa. We use tissues obtained from nasal polypectomy and turbinectomy. Those tissues are either freshly used in an explant model or used to isolate primary structural cells.
McGill-JGH Dubrovsky Molecular Pathology Centre
Director: Dr. Alan Spatz
The advent of targeted therapies for cancer and other diseases has put molecular pathology at the center stage for clinical decision making. Analysis of germ line mutations in cancer has always been part of our molecular diagnostic laboratory portfolio. The identification of actionable driver mutations in cancer, as well as prognostic gene expression signatures have significantly changed the landscape of tumor diagnosis and the role of pathology therein. In addition to classical surgical pathology reports, a molecular pathology report is often needed to guide the most effective therapy for the individual patient.
The McGill-JGH Molecular Pathology Center (MPC) opened at the end of 2013, on the 6th floor of the Segal Cancer Centre. The MPC is dedicated to clinical service, training our residents in molecular pathology, and research in biomarker discovery and validation. The Molecular Pathology group at the Jewish General Hospital provides specialized advanced analytical methods for the detection of mutations associated with various diseases, including several types of tumours. The state-of-the-art technology allows us to shift from single gene to multiplex testing for cost-effective testing, and increased security and performance.
The Molecular Pathology team uses advanced technology and instrumentation, such as automated DNA extractors, targeted next-generation sequencing, real-time PCR cyclers, automated DNA sequencers, high-resolution melt-curve analyzer, High Performance Liquid Chromatography (HPLC) system, transcriptomics, and more recently a proteomics platform. The laboratory provides molecular pathology services to the McGill network, especially to the McGill University Health Centre (MUHC) and other hospitals across the province of Quebec.
The Henry C. Witelson Ocular Pathology Laboratory
Director: Dr. Miguel N. Burnier Jr.
About the Lab
Since January 2000, the Henry C. Witelson Ocular Pathology Laboratory has been bringing together clinicians and researchers from around the world in an attempt to provide an atmosphere that is both enriching and multidisciplinary. Tasked with a triple mission of consultation, education and research, the laboratory provides consultation for patients and their doctors, as well as education, teaching and training for pathologists, oncologists, biologists, and medical and graduate students.
Under the direction of Dr. Miguel N. Burnier Jr., lab members work to discover the mechanisms underlying various ocular diseases including uveal melanoma, retinoblastoma, age-related macular degeneration, ocular toxoplasmosis and other clinical ocular pathologies.
The union of experts from several countries and with varying medical backgrounds has provided the impetus for the laboratory’s success to date. With the addition of new experts every year, the lab strives to translate basic research findings into clinically significant treatment options for the millions of individuals afflicted with these devastating ocular diseases.
One of the defining aspects of the laboratory is the breadth of equipment used and techniques employed by our members on a regular basis. Some examples include:
- Immunohistochemistry / immunocytochemistry - using a state-of-the-art automated immunostaining machine (Ventana Medical Systems)
- Fluorescence microscopy (in vitro and in vivo) - using a laboratory-owned epifluorescence microscope
- Confocal microscopy - using a shared, on-site confocal microscope (Olympus)
- Digital pathology - using high throughput, high resolution slide scanners (Aperio, Roche) for clinical and basic research as well as teaching and training
- Cell culture - including human uveal melanoma, retinoblastoma, lens epithelial and retinal pigment epithelial cell lines, as well as human- and mouse-derived retinal progenitor cells
- Whole transcriptome profiling
- Multiplexed sandwich ELISA arrays - for profiling of growth factors, inflammatory cytokines and angiogenic markers
- Large-scale analyses of human tissues - using our in-house bank of over 600 normal and pathological (retinoblastoma, uveal melanoma, choroidal neovascularization, other) eyes
- Customized computer-based diagnostics - using software generated by engineers in our laboratory
- Whole-genome studies - using fresh, frozen, or paraffin-embedded tissues
- Xenograft models of primary and metastatic uveal melanoma - using rabbit and mouse models developed in-house
- Immunomagnetic isolation of cell subpopulations
- In vitro toxicity and viability studies
- Functional assays - including cell proliferation, invasion and migration
- Flow cytometry - for analysis of cell cycle and culture heterogeneity / homogeneity
- Various blotting techniques
- Real-time PCR
The lab actively seeks out and embraces new technologies and techniques that can improve research efficiency and capabilities. Lab members frequently participate in training programs organized by external bodies in order to add to their own scientific skillsets and those of the lab as a whole. For more information on the lab, please visit the Henry C. Witelson Ocular Pathology Laboratory website.
As a group, we work toward advancing translational research in multiple areas of ocular pathology. The purpose of what we do each and every day is best summarized by the following, a message conveyed to each and every member of our team:
“We don’t do research as an intellectual exercise. We do research because there is a patient at the end of the day.”