MD, PhD, FRCPC
Dr. Michael Pollanen's career has been spent at the interface between pathology and vulnerable populations.
The approach implemented in his work has been to use the autopsy and pathological examination as a basis to study disease and injury.
His background in anatomical pathology, neuropathology, forensic pathology, and cellular and molecular pathology has provided an innovative foundation for key morphologic studies.
The specific methods that Dr. Pollanen uses for his research include:
- gross examination
- protein electrophoresis and Western blotting
- transmission electron microscopy
- atomic force microscopy
- postmortem cross-sectional imaging (CT and MR).
Over the years, Dr. Pollanen's clinical and research activities have become seamlessly interwoven with international capacity development in low- and middle-income countries.
On this basis, he has conducted research and capacity development activities in the following countries, usually under an international organization such as the United Nations or the International Committee for the Red Cross:
- Central African Republic
- East Timor
Over the last 15 years, he has trained several fellows in Canada and the Global South.
My early contributions to the pathology of neurodegenerative diseases provide the base for my current work on nodding syndrome in Uganda.
Nodding Syndrome in Uganda
Nodding syndrome (NS) is a neurologic disease that affects African children.
The syndrome has recurred in three epidemics in last 50 years in Tanzania (1960s), South Sudan (1990s) and Uganda (2000s).
Symptoms usually appear between 5 and 15 years of age with stereotypical head dropping movements (nodding), and grand mal seizures. In the late stage, there is dementia and Parkinsonism.
Multiple children in the same family are often affected by NS. There is no evidence of Mendelian inheritance, but the Acholi tribe is preferentially affected.
The etiology and pathogenesis of NS is unknown although there is an epidemiological and serological correlation with onchocerciasis.
We studied cases of fatal NS and discovered tau pathology.
The NS epidemic has a discrete spatiotemporal and ethnic distribution; thus, our hypothesis is that NS is caused by a convergence of genetic and environmental factors.
Our overall goal is to understand NS at the cellular and molecular levels to determine the cause and pathogenesis of NS to allow for prevention and cure.
Our multidisciplinary approach spans clinicopathologic, biochemical, genetic, epidemiological and environmental/ecological methods.
We believe that NS holds clues that will help unravel the etiology and pathogenesis of sporadic age-related neurodegenerative tauopathies in the western world.
The overall goal of the current project is the clinicopathological (aim 1) and biochemical (aim 2) characterization of NS.
The results of these investigations will be used to develop testable hypotheses on the eitology and pathogenesis of NS, thereby facilitating an ongoing research program.
The future elements of the research program will include:
- Epidemiology/ecology to determine the changes in the environment that occurred at the time of the NS outbreak in Uganda.
- Investigation of neuroautoimmunity in NS.
- Investigation of possible linkage to onchocerciasis.
- Whole genome sequencing in families.
- Determination of putative roles of tau haplotype and HLA association(s).
- Longitudinal clinical studies with sequential videotaping of patients to investigate Parkinsonism and related neurological features.
- Testing hypotheses that emerge from the pilot study.
Specific aim 1: Describe the clinicopathological features that define NS
Use immunohistochemistry to map the topography of neurodegeneration in the central nervous system and describe the clinicopathological hallmarks of NS.
Rationale: Clinicopathologic description of a disease is the first step in mechanistic analysis of pathogenesis and the identification of environmental and genetic factors which caused a disease.
There is no substitute for this fundamental work and failure to undertake it can impair or misdirect hypothesis development. Therefore, our first-step is to make a complete clinicopathological description of NS.
Our collaborative network has already collected all cases that have previously undergone autopsy in Uganda and is actively collecting the clinical data, brains and spinal cords on fatal cases, prospectively.
Informed consent is always obtained for postmortem examination. Our network has now collected 10 cases of fatal NS with a complete clinical history and standardized formalin fixed and paraffin embedded tissue blocks. All blocks have been stained with routine histological methods and can now be studied by immunohistochemistry.
We will undertake comprehensive immunohistochemical studies in NS, map the topography of neurodegeneration in the brain and spinal cord, and to describe the clinicopathological correlations in NS.
Methods: Brains and spinal cords are examined after formalin fixation.
The topographic distribution of the neurodegeneration will be described and a clinicopathologic correlation will be made to determine the clinical hallmarks of the neurodegeneration.
Immunohistochemistry will be undertaken with relevant antibodies to various proteins including:
- tau (various epitopes spanning the N- and C-termini)
- FUS, TAF-1
- protease-resistant prion protein
- myelin basic protein
- GFAP (astrocyte)
- CD68 (activated microglia and macrophages
- CD3, CD4, and CD8 (lymphocytes).
Double labelling experiments to determine the relationships of tau immunoreactivity to glia will be undertaken.
Specific aim 2: Determine the basic biochemical and filament profile of the proteinopathy in NS
Study the biochemistry and structural biology of insoluble brain proteins in NS and determine if NS tau has prion-like characteristics.
Rationale: Proteinopathies occur when constitutively expressed proteins become post-translationally modified, insoluble and then precipitate in the cytosol or extracellular space.
The main proteinopathies involve tau, b-amyloid, a-synuclein, TDP-43, FUS and the protease-resistant prion protein. The most studied protein is tau which has prion-like properties and is implicated in Alzheimer’s disease and other tauopathies.
Methods: Samples of frozen NS brain tissue will be used as the substrate for biochemical studies.
Detergent extracted brain homogenates will be separated into soluble and insoluble fractions by centrifugation and studied by electrophoresis and immunoblotting using many of the same antibodies as employed for immunostaining tissue sections.
Any novel bands identified by electrophoresis that are not captured by immunoblotting will be characterized by mass spectroscopy.
Extracts from NS brain will undergo characterization by electron microscopy with negative staining and epon embedding.
We will also undertake tau propagation experiments, in collaboration.
Pollanen MS, Onzivua S, Robertson J, McKeever PM, Olawa F, Kitara DL, Fong A. Nodding syndrome in Uganda is a tauopathy. Acta Neuropathol. 2018 Nov;136(5):691-697.
Pollanen MS. The pathology of torture. Forensic Sci Int. 2018 Mar;284:85-96.
Pollanen MS. Forensic pathology and the miscarriage of justice. Forensic Sci Med Pathol. 2012. 2012 Sep;8(3):285-9. doi: 10.1007/s12024-011-9299-5. Epub 2011 Nov 25.
Pickup MJ, Pollanen MS. Traumatic subarachnoid hemorrhage and the COL3A1 gene: emergence of a potential causal link. Forensic Sci Med Pathol. 2011 Jun;7(2):192-7. Epub 2010 Nov 18.
Pollanen MS, Perera C, Clutterbuck. Hemorrhagic lividity of the neck: Controlled induction of postmortem hypostatic hemorrhages. American Journal of Forensic Medicine and Pathology. 2009 Dec;30(4):322-6.
Chief Forensic Pathologist (founding) of the Ontario Forensic Pathology Service (and Deputy Chief Coroner)
Examiner in anatomical pathology for the Royal College of Physician and Surgeons of Canada
Member of the forensic advisory board for the International Committee for the Red Cross
Associate Member of Graduate Studies, University of Toronto
Director, Forensic Pathology Fellowship Program (international), University of Toronto
Honours and Awards
Vice-Chancellor’s award, University of the West Indies, 2018
Richard G. Hegele Award in Research and Innovation, Department of Laboratory Medicine and Pathobiology, 2017
John B. Walter Prize for Course Design and Development, Department of Laboratory Medicine and Pathobiology, 2016
Distinguished Pathologist’s Award, Ontario Association of Pathologists, 2015
Excellence in Postgraduate Medical Education award, University of Toronto, 2015
Global Forensic Capacity Development Program