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Associate Scientist, Cancer Therapeutics, Ottawa Hospital Research Institute
Attending Staff Neuropathologist, Department of Laboratory Medicine, Ottawa Hospital, Civic Campus, Ottawa, Ontario, Canada
Assistant Professor, Department of Pathology, University of Ottawa, Ottawa, Ontario, Canada
Research Interests
intranuclear inclusions
tubulin
Alzheimer's disease
Parkinson's disease
neuropathology
frontotemporal dementia
Research Activities
Neuronal Intranuclear Inclusions in Health and Disease
 a) Tubulin-Immunoreactive Intarnuclear Inclusions in the Human Brain. Our group is exploring a novle type of intranuclear inclusion body in the normal human brain which we feel might reveal clues to intranuclear inclusion formation in neurodegenerative disease. These tubulin-immunoreactive neuronal intranuclear inclusions are present in the normal human brain (Woulfe and Munoz, 2000), and in certain brain tumours (ependymomas and gangliogliomas; Woulfe 2000). We have also demonstrated that these inclusions are significantly and substantially reduced in Alzheimer's disease. More recently, we have identified immunoreactivity for other proteins associated with these inclusions which could provide clues as to their function. We believe that these enigmatic intranuclear inclusions are the same rod-like inclusions described by the classical microscopists as early as 1894. These structures are thought to be related to neuronal activity, an observation that is interesting in the context of our findings in Alzheimer’s disease. The results of these ongoing studies may have important implications with respect to understanding the pathogenesis of Alzheimer's disease and other neurodegenerative diseases.
 b) Ubiquitinated Neuronal Intranuclear Inclusions in Frontotemporal Dementia
We identified a subgroup of patients with this unique non-tau, non-synuclein related form of frontotemporal dementia. In these patients, abundant ubiquitinated neuronal intranuclear inclusions were found. Ubiquitinated intranuclear inclusions are a pathological feature of trinucleotide repeat disorders. The presence of intranuclear inclusions correlated with distinctive clinical features within the subjects, including a family history. The nosology of this group of diseases is in a state of flux characterized by ongoing debate among "lumpers" and "splitters". Our results would suggest that frontotemporal dementia of motor neuron disease type is a unique category, within which there is a neuropathologically-defined subset of patients. The presence of intranuclear inclusions in these patients may provide a clue to the pathogenesis of the disease.
Awards
Menek Goldstein Research Scholar Award: National Parkinson Foundation
Morrison H. Finlayson Award from The Canadian Association of Neuropathologists
Canadian Society for Clinical Investigation Resident Research Award
Physicians Services Incorporated (PSI) Resident Research Prize
Most Recent Publications (provided by The Ottawa Hospital Library Database)
Woulfe J;Gray DA;Mackenzie IR;, (2009 Sep 21), FUS-Immunoreactive Intranuclear Inclusions in Neurodegenerative Disease, Brain Pathol, -> view abstract
Gagnon J;Mayne J;Mbikay M;Woulfe J;Chretien M;, (2009), Expression of PCSK1 (PC1/3), PCSK2 (PC2) and PCSK3 (furin) in mouse small intestine, Regulatory Peptides, Vol.152, Issue 3-Jan, 54-60 -> view abstract
Woulfe J;, (2008 Nov), Nuclear bodies in neurodegenerative disease. [Review] [159 refs], Biochimica et Biophysica Acta, Vol.1783, Issue 11, 2195-2206 -> view abstract
Mackenzie IR;Foti D;Woulfe J;Hurwitz TA;, (2008 May), Atypical frontotemporal lobar degeneration with ubiquitin-positive, TDP-43-negative neuronal inclusions, Brain, Vol.131, Issue Pt:5, 5-93 -> view abstract
Prichett W;Milman P;Gagnon J;Munoz DG;Woulfe J;, (2007 Oct), Intranuclear rodlets in human pancreatic islet cells135, Pancreas, Vol.35, Issue 3, 207-211
Qu D;Rashidian J;Mount MP;Aleyasin H;Parsanejad M;Lira A;Haque E;Zhang Y;Callaghan S;Daigle M;Rousseaux MW;Slack RS;Albert PR;Vincent I;Woulfe JM;Park DS;, (2007 Jul 5), Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease, Neuron, Vol.55, Issue 1, 37-52 -> view abstract
Micu I;Ridsdale A;Zhang L;Woulfe J;McClintock J;Brantner CA;Andrews SB;Stys PK;, (2007 Jul), Real-time measurement of free Ca2+ changes in CNS myelin by two-photon microscopy, Nature Medicine, Vol.13, Issue 7, 874-879 -> view abstract
Cairns NJ;Bigio EH;Mackenzie IR;Neumann M;Lee VM;Hatanpaa KJ;White CL;Schneider JA;Grinberg LT;Halliday G;Duyckaerts C;Lowe JS;Holm IE;Tolnay M;Okamoto K;Yokoo H;Murayama S;Woulfe J;Munoz DG;Dickson DW;Ince PG;Trojanowski JQ;Mann DM;, (2007 Jul), Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration70, Acta Neuropathol, Vol.114, Issue 1, 5-22 -> view abstract
Woulfe JM;, (2007 Feb), Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress. [Review] [357 refs], Neuropathology & Applied Neurobiology, Vol.33, Issue 1, 2-42 -> view abstract
Woulfe JM;Prichett-Pejic W;Rippstein P;Munoz DG;, (2007 Feb), Promyelocytic leukaemia-immunoreactive neuronal intranuclear rodlets in the human brain, Neuropathology & Applied Neurobiology, Vol.33, Issue 1, 56-66 -> view abstract
Note: This is not a complete list of publications. More publications may be available in The Ottawa Hospital Library database and Pubmed (search by last name and initials).
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Civic Campus
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