Summer 2016 – Special Edition
Faculty of Medicine, University of Ottawa
Research Newsletter of the Basic Science Departments
Chronic Pharmacological mGluR5 Inhibition Prevents Cognitive Impairment and Reduces Pathogenesis in an Alzheimer Disease Mouse Model
In a paper published in Cell Reports, Dr. Stephen Ferguson (CMM) of the uOttawa Brain and Mind Research Institute (uOBMRI) and Tier 1 Canada Research Chair in Brain and Mind, presents new findings that suggest that blocking the mGluR5 glutamate receptor in the brain results in improved memory and reduces neuronal pathology in Alzheimer’s mice. Tests show that a drug called CTEP can be used to block mGluR5 and prevent, or even reverse, cellular pathology in Alzheimer’s disease. “CTEP has the potential to prevent memory loss if it is successful in humans,” says Ferguson, who is now working on expanding this research to further understand the mechanism by which mGluR5 contributes to Alzheimer’s pathology and how its inhibition using CTEP can reverse cognitive decline in Alzheimer’s patients.
Global health diplomacy: A critical review of the literature
Global health diplomacy (GHD) describes the practices by which governments and non-state actors attempt to coordinate and orchestrate global policy solutions to improve global health. In a recent Social Science and Medicine article, School of Epidemiology, Public Health and Preventative Medicine (SEPHPM) professor Dr. Ron Labonté and uOttawa colleagues Drs. Arne Ruckert and Vivien Runnels conducted a critical literature review on the driving forces behind, and theoretical explanations of, GHD. Upon completion of their literature search, they found a lack of rigorous theorizing about GHD and fragmentation of the GHD literature which is not clearly structured around key issues and their theoretical explanations. The authors linked the findings from the GHD literature to how theoretical concepts used in International Relations (IR) have been, and could be, invoked in explaining GHD more effectively. A theoretical taxonomy was developed to explain GHD outcomes based on a popular categorization in IR, identifying three levels of analysis (individual, domestic/national, and global/international) and the driving forces for the integration of health into foreign policy at each level. In an effort to better understand GHD, the authors maintain that wider collaboration between IR and global health scholars will be necessary. This article is one output of an ongoing, multi-year comparative study of global health diplomacy, funded by CIHR, involving researchers in Canada, Mexico, Brazil and Chile.
Discovery could reduce the need for preventive mastectomy in BRCA1-mutated breast cancer
One in nine Canadian women is expected to develop breast cancer throughout her lifetime, and one in 30 will die from it. Preventing breast cancer at the cellular level however, may be a possibility, after research published in Cell Stem Cell by Dr. Christine Pratt (CMM) uncovered why breast cells with the BRCA1 gene mutation are at high risk for evolving into tumours. When a woman inherits a mutation of the BRCA1 gene, the gene may not be able to repair faulty DNA, increasing the risk of genetic mutations and cancer. During a monthly cycle in humans, stem cells within the breast undergo a phase called proliferation, where cells rapidly multiply in response to the hormone progesterone. Dr. Pratt and her team have discovered that if these cells lack BRCA1, they accumulate DNA damage as they multiply, which triggers NF-κB, a protein complex normally involved in the proliferation of immune cells. “The activation of NF-κB leads to increased cell proliferation that no longer requires progesterone, resulting in even more DNA damage,” says Pratt. “In cells with a BRCA1 mutation, the DNA cannot be properly repaired.” Together, these factors strongly increase the risk of more mutations that can lead to breast cancer. The finding that NF-κB is pivotal to the development of breast cancer in BRCA1 mutation carriers opens the door for prevention therapies targeting the NF-κB protein.
K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo
Receptor interacting protein kinase 1 (RIPK1) is a protein that participates in cell survival and cell death signaling, however, the intricacies of these signaling mechanisms and the consequent impact against inflammatory conditions is not clear. In a recent Cell Death and Differentiation article, Dr. Subash Sad’s group (BMI) has tested the impact of a K45A mutation in one of the kinase regions of RIPK1. They have shown that mutation in this kinase region results in complete resistance of cells to undergo necrosome signaling, which results in resistance to cell death by necrosis (necroptosis). More interestingly, they have shown that introduction of this mutation results in impairment in cytokine signaling following infection, which leads to compromised survival following an infectious challenge. Thus, the authors conclude that the kinase function of RIPK1 is not only important for cell death by necroptosis, but it also has a key role in promoting cytokine signaling and host response to inflammatory stimuli. Authors conclude that delineation of the mechanisms through which the kinase region of RIPK1 influences host outcome would lead to the development of novel therapeutics against inflammatory diseases caused by pathogens or sterile triggers.
Congratulations to the following Faculty of Medicine members from our Basic Science Departments who were awarded grants as principal applicants in the latest CIHR Project Grant competition:
• Jean-François Couture
• Daniel Figeys
• Michael Downey
• Stephen Ferguson
• Morgan Fullerton
• Manisha Kulkarni
• Wenbin Liang
• David Lohnes
• Benjamin Rotstein
• Marie-Hélène Roy Gagnon
• Jean-Claude Béïque
• Balwant Tuana
• Nadine Wiper-Bergeron
Congratulations to Drs. Mona Nemer and David Park who were successful in the latest CIHR Foundation Grant competition.
Congratulations to Dr. Richard Hébert for his recent Kidney Foundation of Canada Grant for his project “The renal PGE2/EP3 system affects kidney concentrating mechanisms and diabetic polyuria”.
Congratulations to the following researchers on receiving Heart and Stroke Foundation grants
• David Park
• Daniel Figeys
• Dale Corbett
• Monique Potvin-Kent
Congratulations to Dr. Daniel Figeys who recently received a grant from the Ontario Genomics Institute.
Congratulations to Drs. Dale Corbett and Baptise Lacoste for receiving a HSF Canadian Partnership for Stroke Recovery Grant for their project “Engaging skeletal muscle and vascular plasticity to promote hindlimb functional recovery in a rat model of ischemic stroke”.
Congratulations to Dr. David Park who was awarded $147,754.62 over three years from the Weston Brain Institute.
Congratulations to Drs. John Copeland and Qiao Li who were successful in obtaining Cancer Research Society Operating Grants. Dr. Copeland will be funded through a Cancer Research Society/University of Ottawa Operating Grant.
This quarterly newsletter features high level achievements by researchers in the Basic Science Departments. If you have a recent publication in a top journal, new grant or award, we would like to hear about it! Please contact: firstname.lastname@example.org