Room: Rm. 2414 RGN Neurology
Email: [email protected]
Director, Neuroscience Program
Bhargava Research Chair in Neurodegeneration | Ottawa Hospital Research Institute
Co-Director | Parkinsons Research Consortium
Professor, uOttawa Brain & Mind Research Institute
Dr. Michael 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 b protein by cultured cells (Nature 1992; 359: 322-325) into biological fluids (Nature1992; 359: 325-327), an essential building block for the ‘amyloid hypothesis’ of Alzheimer disease.
Following residency training in general medicine in Vienna (1992-1995), Dr. Schlossmacher completed adult neurology training in the Harvard Longwood Neurology Program (1995-1999) 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 moved to Ontario in late 2006; he 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.
Parkinson disease (PD) is a neurodegenerative disease that directly affects over 100,000 Canadians and over 1,000,000 people in North America. No new cause-directed therapies have been developed since the discovery of dopamine deficiency in PD brain by O. Hornykiewicz in 1961. Presently available therapies do not change the course of PD, do not treat its many non-motoric symptoms, and do not address the root causes of parkinsonism. The failure to deliver new, cause-directed therapies is rooted in the lack of breakthroughs in our understanding of both the fundamental causes of the disease and the underlying molecular mechanism(s) through which it destroys dopaminergic (and other) neurons and causes neurodegeneration.
The goal of the research efforts in the Schlossmacher laboratory is to contribute to the clinical improvement of individuals living with PD. Specifically, we are addressing this from three distinct avenues:
1. We seek to contribute to the development of cause-directed therapies. In doing so, we are focusing on the molecular processes that drive neurodegeneration. Specifically, we are studying the mechanisms by which PD-linked genes (including a-synuclein, Parkin, LRRK2 and GBA1) lead to neuronal dysfunction and the pathways that govern their metabolism. Of note, we were the first neuroscience team to identify a role for LRRK2 in the immune system in 2011; we also co-discovered biochemical links between lysosomal dysfunction, including those caused by mutations in GBA1 and cathepsin D, and altered a-synuclein processing in mammalian brain.
2. We are developing better animal models of young- and late-onset PD as well as dementia with Lewy bodies (DLB), which in addition to providing valuable insights into disease processes, will serve as platforms for pre-clinical testing of PD-targeted therapeutics. The latter is pursued in part through partnerships with industry collaborators.
3. We are continuing our biomarker work to be able to clinically diagnose the disease in those with likely a-synuclein aggregation in the brain. In 2007, these efforts led to the first identification of a reduction in total a-synuclein concentrations in cerebrospinal fluid specimens of patients with a-synuclein-related disorders (PD, DLB) in their nervous system. Our biomarker efforts also made possible the commercialization of a sandwich ELISA for the quantification of a-synuclein in 2011. It was initially developed by our team, including Dr. Brit Mollenhauer of Germany and Dr. Omar El-Agnaf of United Arab Emirates, was further optimized here at the OHRI and then subsequently by Covance Inc.
Ms. Nancy MacDonald
E-mail: [email protected]
Potential trainees, please send inquiries to:
Dr. Julianna Tomlinson
To explore mechanisms how four genes linked to Parkinson disease promote cell death: alpha-synuclean, GBA1, LRRK2, Parkin.