Highlights from the past year include publishing: “Energy cost at rest and during exercise in tetraplegia: the need for specific diet and exercise guidelines” in Frontiers in Exercise Physiology and the invited review “A new conceptual framework for the integrated neural control of locomotor and sympathetic function: implications for exercise after spinal cord injury” in Applied Physiology Nutrition and Metabolism. The research in both of these papers will have implications for the health of those living with spinal cord injury (SCI) and the energy expenditure paper results have been translated into everyday language and published in two SCI-magazines. In addition, we have continued implementation of our CFI and Will to Win-funded Human Spinal Cord Injury Research Centre for Health, Balance and Motor Control Facility. I continued to serve as a member of the Natural Sciences and Engineering Research Council’s Research Tools and Instruments national peer review committee, and enjoyed my experience serving on the international letter of intent peer review panel for the Craig H. Neilsen Foundation’s SCI Research on the Translational Spectrum Funding Opportunity.
In 2017-2018, my lab has published 3 research articles, through local and national collaborations. I have been invited to the Canadian Oxidative Stress consortium to introduce my research to my Canadian colleagues. I have also established new collaborations with researchers in the United States and Europe.
This year my program was awarded a major two‐year grant in the field of Spinal Cord Injury from the European foundation of Wings for Life (€200,000). Additionally, my research in the field of cell death has expanded to neurodegenerative diseases and we have presented our latest findings at the Society for Redox Biology and Medicine. Our work was selected for podium presentation and my post-doctoral fellow has been recognized through a competitive travel award from the Society. This manuscript has been recently submitted.
Throughout 2018 I have continued in leadership roles both within the Unit and also relating to teaching within the Max Rady College of Medicine. I am the Division Head of the Neurosciences and Spinal Cord Injury Division within the Department of Physiology & Pathophysiology and the Course Director for the “Foundation of Medicine” course within the Undergraduate Medical Education, Med I curriculum. I serve on the Pre‐Clerkship Curriculum, Pre‐Clerkship Evaluation, and Academic Appeals committees within the College of Medicine. I am also a major content contributor and instructor within the Med I “Neuroscience I” course. I also serve on the Departmental Graduate Program Committee and am the Course Director (or Co-Director) for a variety of graduate courses, as well as Pathophysiology courses within the College of Pharmacy. I have been nominated by the Manitoba Medical Students Association for teaching awards in their “Inspiration” and/or “Innovation” categories for 3 successive years. During 2018 I was also pleased to re-connect with a former trainee from our group (Dr. Yue Dai, PhD with Dr. Jordan, followed by PDF training with me). We published work that I had originally started as a ‘side-project’ while Dr. Dai was a student. We had collaborated on how frequency / current relationships of motoneurons could be assessed during walking movements, and he has subsequently re-examined this with updated computer modeling techniques in his own laboratory in China. We have published the resulting study during 2018.
I was honoured to be asked by the journal Applied Physiology, Nutrition & Metabolism (APNM) to be Guest Editor of a Special Edition of the journal entitled “The Nervous System and Exercise.” All requested invited reviews have been submitted and reviewed, and are in press. I also published a review in this issue entitled “Mechanisms and functional implications of motoneuron adaptations to increased physical activity” (co-authored with Chris MacDonell). I was pleased to accept an invitation to speak at Simon Fraser University in April 2018, the title of which presentation was “I sing the spinal cord electric: Activity-related plasticity of spinal cord neurons and circuits.” Recently, I was asked to chair the Manitoba Spinal Cord Injury Research Committee (MSCIRC) beginning April 2019, which invitation I have accepted. On October 31, at the Annual Canadian Society for Exercise Physiology Conference in Niagara Falls, the President’s Lecture in my honour will be given, titled “Motor Neurons, Muscle & Mechanisms: a PHILharmonious Approach to Studying Neuromuscular Plasticity.”
In May 2018 I was invited to present a keynote address at the Symposium providing homage to Dr. Serge Rossignol, where I highlighted recent work in my lab using Designer Receptors Exclusively Activated by Designer Drugs (DREADDS), to show that locomotion can be improved in paraplegic rats by activating grafted cells below the lesion using chemogenetic tools. Our lab has developed a mouse model with excitatory DREADDS expressed in all 5-HT neurons. This mouse model will provide a tool for establishing the functional roles for descending 5-HT neurons, and it will provide a source of cells for grafting that will improve on the current method of using a viral vector. In July I was invited to provide an overview of the role of 5-HT7 receptors in the control of movement at an International Meeting in Ireland. I also collaborated on an invited review of the role of 5-HT in the control of locomotion to be published in Current Opinion in Physiology. My work on fictive locomotion in adult rodent preparations continues and is one of only a few laboratories in the world with this capability.
This year my group had a productive year at all fronts. We received several grants, notably a sizable 5-year grant from the Canadian Institute of Health Research (CIHR) that supports our neural stem cell transplantation research. We have published several high impact articles in top-tier journals including 3 papers in GLIA, 2 papers in the Journal of Neuroinflammation and one in the Journal of Controlled Release that has implemented a new microcarrier-based drug delivery platform for our spinal cord injury and MS therapeutics. This work was entirely performed by my team and was published in a top journal in the field of drug delivery (IF of 8).
This year I received a Merit Award from the University of Manitoba for my outstanding contributions to Scholarly Research, Teaching and Service. I have been also nominated by the University of Manitoba for a CIHR Gold Leaf Prize for Outstanding Achievements by an Early Career Investigator. I was honored to be elected by the Canadian Neuroscience Community to the Board of Directors of the Canadian Association of Neuroscience for a three-year term. I served on the Scientific Advisory Committee of the 2018 International Neurotrauma Symposium that was held in Toronto. I also served on the review board of operating grants and fellowships for the New York State Department of Health and the Spinal Cord Injury Research Board (SCIRB) and the CIHR Cellular and Molecular Neuroscience panel (NSB) for both Spring and Fall competitions. I have been invited as an evaluator and chair for the Mid-term symposium of the funded consortia of the European ERA-NET NEURON in Germany. I have joined the editorial board of Frontiers in Neurology and BMC Neuroscience. At the U of M, I have participated in several committees including Search Committee for the Buhler Chair in Stem Cell Research, the Henry G. Friesen Chair in Metabolic & Endocrine Diseases Renewal Committee, Promotion and Tenure, and Major Awards. I have completed a two-term membership (6 years) in the Undergraduate Medical Education Progress Committee.
In 2018, I delivered eight presentations as keynote or invited speaker including 5 national presentations in Toronto, Ottawa and Calgary. I was the keynote speaker of the Calgary StemCellTalks and the Alberta MS Network in May 2018. Our spinal cord injury and multiple sclerosis research received media attention. Notably, our MS research was featured by the Winnipeg Free Press (https://www.winnipegfreepress.com/arts-and-life/life/health/u-of-m-researchers-battle-ms-from-new-angle-483291013.html) and by CBC Radio-Canada “Sclérose en plaques: des travaux porteurs d’espoir."
My trainees were recognized this year through 15 research prizes, recognition and studentships. Most notably, Arsalan Alizadeh was invited to deliver the Drewry Memorial Lecture in 2018 as the recipient of the 2017 Drewry Award for Excellence of Research in the Health Sciences. Chris Hart received two Gold Medal Poster prizes and was also honored to be invited by the Gairdner Foundation to attend the 2018 Gairdner Symposium and Gala in Toronto and meet with Gairdner laureates. Arsalan Alizadeh received the Hilary Kaufman Lerner Memorial Fund from the Rady Faculty of Health Sciences that is awarded to top research trainees/residents who work on demyelinating conditions. Graham McLeod (BSc Med Student) received four major awards including Award to top BSc Med students to represent Manitoba in the National Medical Student Forum in Galveston, Texas in spring 2019, Award for the best BSc Med thesis with potential for commercial applications, MMSF thesis award, and Award for Outstanding BSc Med Presentation. My laboratory also celebrated graduation of four graduate and BSc Med students who defended their thesis high distinctions.
I was invited as senior and corresponding author to write two major reviews in highly reputable journals on the topic of electrical synapses, along with two co‐authors. These reviews focus on three general issues concerning electrical synapses. First, from a historical perspective, the field of electrical synapses in the mammalian CNS appeared to emerge relatively suddenly at the turn of the last century, and has progressed at a relatively rapid pace. These two points have left those outside the field somewhat behind and perplexed, wondering how and why did all this happen, and what caused this sudden transformation in knowledge. It is therefore instructive to consider the multiple discoveries and technological advances that initially enabled the revolution in understanding of electrical synapses in higher vertebrates and convey this to a broad neuroscience audience. Such advances include identification of connexin proteins, especially those forming neuronal gap junctions (e.g., connexin36, Cx36), novel approaches to ultrastructural detection of gap junctions, and application of definitive methods for analysis of neuronal electrical coupling. Second, despite progress on and acceptance of the widespread distribution of electrical synapses in the mammalian CNS and their functional contributions to neuronal network activity, there are still numerous regions in brain and spinal where Cx36‐containing gap junctions are abundant as seen by our immunofluorescence studies, but have otherwise received little attention. These sites have not been investigated for either cellular, subcellular or ultrastructural localization of those junctions, and have not been subject to electrophysiological analysis. Consequently, their potential contribution to these structures. Third, electrical synaptic transmission between neurons is regulated by numerous neurotransmitters and modulators, and by alterations in the phosphorylation state of Cx36. However, little is known about how modifications in Cx36 trafficking and changes in rates of gap junction turnover, including assembly and disassembly, could contribute to short or long term regulation of transmission at electrical synapses. Our identification of the macromolecular protein components of Cx36‐containing gap junctions that form electrical synapses provides opportunities to consider novel mechanisms whereby intracellular signaling pathways could influence the formation and structural integrity of these synapses and thereby contribute to regulating strength of electrical coupling. These components include structural and scaffolding proteins, transcellular adhesion proteins, and a variety of regulatory and signaling proteins.
In collaboration with Dr. Katinka Stecina, we are continuing our investigation of the locomotor propriospinal relay system. Our hypothesis, based on our earlier work using an in vitro neonatal rat model, is that this system is critical for the activation of locomotion in adult mammals (including humans). This technically demanding series is now almost complete. We believe we have confirmatory evidence of the existence of such a system.
The only constant variable in my lab’s research activity in the past year was change. With the relocation of my mouse laboratory this summer, we are now one step closer to the establishment of the new human research facility! The new transcranial magnetic stimulator, although not utilized in the human function lab yet, was put to good use during our NeuroTalks day science outreach activities. It was a popular hit with the high school students! Other ongoing animal research experiments either in collaboration with Dr. Schmidt and Dr. Larry Jordan or my personal research projects are developing well with results being published in the very near future.