Michael Schlossmacher
Senior Scientist, Neuroscience
Ottawa Hospital Research Institute
Director, Neuroscience Program
Ottawa Hospital Research Institute
Bhargava Research Chair in Neurodegeneration, Division of Neurology
The Ottawa Hospital
Professor, Faculty of Medicine
University of Ottawa
Neurologist, Division of Neurology, Department of Medicine
The Ottawa Hospital
Member
University of Ottawa Brain and Mind Institute
Research Interests
Since 2000, I have pursued work as a physician-scientist focusing on Parkinson disease (PD), Lewy body dementia (DLB) and multiple system atrophy (MSA). Since opening my new laboratory at the OHRI in 2007, my team has focused on: (i) to investigate the pathogenesis of different forms of parkinsonism, such as late- vs. young-onset PD and delineate disease mechanisms; in this effort, we are led by autopsy findings. (ii) to build new animal models that restage aspects of neuropathology that are linked to mutations in one of four PD-associated genes. (iii) to develop a simple-to-impute formula for PD risk (PREDIGT Score) that is based on five risk categories and could enable an early diagnosis, even independent of a neurologist.
Brief Biography
Dr.
Schlossmacher is a clinician scientist focused on improving the lives of
individuals with neurodegenerative diseases. In July 1987, following completion
of medical school in Vienna, Austria, he began graduate studies in human
biology. A Fulbright Commission scholarship enabled him to visit Harvard
University. He subsequently pursed post-doctoral work on the molecular
pathology of Alzheimer disease in the laboratory of Dr. Dennis J. Selkoe
(1988-1992). This led to his co-discovery of the physiological release of amyloid
beta protein by cultured cells into biological fluids (Nature 1992), an essential
building block for the ‘amyloid hypothesis’ of Alzheimer disease.
Following
residency training in general medicine in Vienna (1995), Dr. Schlossmacher
completed adult neurology training in the Harvard Longwood Neurology Program
(1999) and a clinical fellowship in movement disorders at Brigham & Women's
Hospital and Massachusetts General Hospital (1999-2001). Since 2000, he has
focused his research activities on Parkinson disease, initially under the
mentorship of Drs. Dennis J. Selkoe, Kenneth S. Kosik and Peter T. Lansbury. In
2003, he became an independent investigator at the Center for Neurologic
Diseases at Brigham & Women's Hospital, and was appointed Assistant
Professor in Neurology at Harvard Medical School in 2004.
Recruited by the OHRI
and University of Ottawa with support from the Canada Research Chair Program,
Dr. Schlossmacher opened a new laboratory as a member of the Parkinson’s
Research Consortium Ottawa in early 2007. In October 2012, he was named the Bhargava
Research Chair in Neurodegeneration at the OHRI. The appointment was made
possible through the generous support from Mrs. Uttra and Mr. Sam Bhargava and
their family. In 2015, he was appointed Director of the Neuroscience Program.
Selected Publications
Li J, Mestre TA, Mollenhauer B, Frasier M, Tomlinson JJ, Trenkwalder C, Ramsay T, Manuel D, Schlossmacher MG. Evaluation of the PREDIGT score's performance in identifying newly diagnosed Parkinson's patients without motor examination. NPJ Parkinsons Dis. 2022 Jul 29;8(1):94. doi: 10.1038/s41531-022-00360-5. PMID: 35906250; PMCID: PMC9338052.
Schlossmacher MG, Graybiel A. Conversations with Dr. Oleh Hornykiewicz, Founding Father of the Dopamine Era in Parkinson’s: How Do You Wish to be Remembered? Mov Disord. 2020 Nov;35(11):1922-1932. doi: 10.1002/mds.28316. Epub 2020 Oct 14. PMID: 33053225; PMCID: PMC7756664.
Tokarew, Jacqueline M., et al. "Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites." Acta neuropathologica 141.5. 2021; 725-754.
Oliveira, Luis, et al. "Alpha-synuclein research: defining strategic moves in the battle against Parkinson’s disease." npj Parkinson's Disease 7.1. 2021; 1-23.
Sircar, Esha, et al. "Neurodegeneration: Impact of S-nitrosylated Parkin, DJ-1 and PINK1 on the pathogenesis of Parkinson's disease." Archives of Biochemistry and Biophysics 704. 2021; 108869.
Sanyal, Anwesha, et al. "Lysosome and inflammatory defects in GBA1-mutant astrocytes are normalized by LRRK2 inhibition." Movement Disorders 35.5 2020; 760-773.
Shutinoski B, et al. Lrrk2 alleles modulate inflammation during microbial infection of mice in a sex-dependent manner. Sci Transl Med. 2019 Sep 25;11(511). pii: eaas9292. doi: 10.1126/scitranslmed.aas9292.
Tomlinson JJ et al. Holocranohistochemistry enables the visualization of α-synuclein expression in the murine olfactory system and discovery of its systemic anti-microbial effects. J Neural Transm 2017; 124(6): 721-738
Schlossmacher MG et al. Modelling idiopathic Parkinson disease as a
complex illness can inform incidence rate in healthy adults : the PREDIGT
score. Eur J Neuroci. 2017;
45(1) :175-191
Cullen V* et al. Acid beta-glucosidase mutations linked to Gaucher disease, Parkinson's and Lewy body dementia dysregulate alpha-synuclein in vivo. Ann Neurol 2011;69:940-53
*This paper was awarded the editor's ‘Annals of Neurology Prize' in 2012
Hakimi M et al. Parkinson's-linked
LRRK2 is expressed in immune cells and upregulated after the recognition of
microbial structures. J Neural
Transm 2011;118:795-808
Mollenhauer B* et al. Cerebrospinal fluid values of alpha-synuclein and tau in patients
presenting with parkinsonism. Lancet Neurol
2011;10:230-40 and Lancet Neurol 2011;10:681-3;
*See also the opinion piece published
in: Lancet Neurol 2011;10(3):203-5
Diseases, conditions and populations of interest
Research and clinical approaches
