The Canadian Association for Neuroscience is very proud to present Arkady Khoutorsky, PhD, Associate Professor in the Department of Anesthesia and Faculty of Dental Medicine and Oral Health Sciences at McGill University, with a 2023 CAN New Investigator Award. Prof. Khoutorsky is making disruptive contributions in two key areas of neuroscience: translational control in neurological disorders and chronic pain, and his work in both areas is bringing forward new concepts for developing novel types of therapeutic interventions.
One of Prof. Khoutorsky’s greatest impact to date has been the introduction of novel molecular concepts to the understanding of pain regulation and the initiation of pathological pain. Chronic pain is caused by sensitization of the nervous systems via numerous mechanisms that involve structural and functional plasticity and new gene expression. Prof. Khoutorsky has recently identified a novel structural plasticity mechanism in peripheral pain neurons (called nociceptors). They showed that tissue inflammation induces growth and branching of free nociceptive nerve endings in the epidermis, contributing to pain hypersensitivity, and demonstrated that this mechanism is mediated via mTORC2. In another study, his research revealed a new mechanism by which spinal microglia promote pain. He found that neurons transmitting pain signals to the brain (projection neurons) are exclusively surrounded by extracellular matrix structures called perineuronal nets (PNNs) and demonstrated that the activation of microglia after nerve injury leads to the degradation of PNNs around these neurons, resulting in increased neuronal activity and thus pain. In another innovative study, his team studied the effect of nerve injury on gene expression and found one specific protein, called Apoe, which was upregulated in the chronic phase of neuropathic pain in mice. The team also showed a strong link between polymorphisms in the APOE gene and chronic, but not acute pain, in people. These exciting findings have led to a better understanding of many factors that can lead to chronic pain.
Prof. Khoutorsky has also made several discoveries relating to regulation of protein synthesis in neurological disorders. His team discovered cell-type specific dysregulation of protein synthesis in a mouse model of Fragile X syndrome (Fmr1 null mutant mice) and in brain samples from humans with Fragile X syndrome that is changing our understanding of this disease. In another study, they discovered a mechanism by which repeated anesthesia in juvenile mice leads to long-lasting cognitive deficits and showed a beneficial effect of intranasal insulin administration in preventing repeated anesthesia- induced memory deficits. In addition, he has published several papers related to translational control in the regulation of seizure threshold, cerebellar functions, and the role of a specific protein called MNK1 in synaptic plasticity and memory.
Overall, Arkady is a rare and outstanding young scientist, a true rising star. His discoveries have been impactful to the fields of chronic pain and neurological diseases. Given his drive, creativity, intelligence and insights I am confident that he will continue to be transformative as his career progresses. -Michael W. Salter MD PhD FRSC Senior Scientist, Hospital for Sick Children & Professor of Physiology University of Toronto
Prof. Khoutorsky’s publication record is impressive. His h-index already stands at 35, with >3800 total citations. What is even more remarkable than simply his volume of published work is the quality of the venues he publishes in. In 2021, Prof. Khoutorsky published papers, all as senior author, in Progress in Neurobiology (2020 impact factor: 9.4), Proc. Natl. Acad. Sci. USA (12.2), Cell Reports (9.4), and Scientific Reports (4.4). In 2022, Prof. Khoutorsky was senior author on papers published in Nature Communications (impact factor: 14.9), two in Journal of Clinical Investigation (14.8), Brain (15.3), and Science (47.7). Importantly, these contributions are truly transformative.
Prof. Khoutorsky has won several early career awards, including being named a NARSAD Young Investigator (for work on Fragile X syndrome), and winning the prestigious Rita Allen Scholar award from the Rita Allen Foundation and the American Pain Society. In addition to obtaining two FRQS salary awards, he has been named a McGill William Dawson Scholar. In terms of grant funding, he has been particularly successful at the national level (multiple NSERC and CIHR grants) and internationally (ERA-NET NEURON program of the European Union and SFARI). With this support, Prof. Khoutorsky runs a bustling lab and is now training some of the most exciting young scientists in the field. He has supervised eight graduate students, three postdoctoral fellows, three research associates and more than 18 undergraduate research projects.
In addition to research excellence, he has taken on leadership roles at McGill including chairing the events committee of the Alan Edwards Centre for Research on Pain, one of the country’s leading pain centres. He has served as a peer reviewer on the CIHR NSB panel which attests not only to his service, but also to the very high regard with which he is held by the neuroscience community. In addition, he teaches two courses through Dentistry and one neuropharmacology course. He is a member of more than a half dozen committees at McGill.
Taken together, Prof. Khoutorsky’s work has resulted in discoveries that substantially advance the understanding of mechanisms underlying pathological pain and the role of translational control in brain functions in health and disease. In both areas, Prof. Khoutorsky’s discoveries are bringing forward new concepts for developing novel types of therapeutic interventions. Prof. Khoutorsky is an outstanding young scientist who has made several ground-breaking discoveries across various areas of neuroscience and has already achieved national and international visibility at an early stage of his career.
The Canadian Association for Neuroscience is proud to present him with a 2023 CAN New Investigator Award.
Learn more on the Khoutorsky lab website: https://arkady-khoutorsky.lab.mcgill.ca/
Five most significant contributions
Tansley, S., N. Gu, A. Guzmán, E. Muñoz-Pino, C. Wong, N. Yousefpour, W. Cai, J. Heal, N. Wu, A. Castonguay, Lean, E. Muir, M. Prager-Khoutorsky, J. Zhang, J. W. Fawcett, L. Diatchenko, A. Riberio-da-Silva, Y. De Koninck, J. Mogil, A. Khoutorsky. (2022). Microglia-mediated degradation of perineuronal nets promotes pain. Science, Jul;377(6601):80-86.
Wong, C, O. Barkai, S. Lev, Tansley, N. Yousefpour, K. Lister, M. Latif, M. Prager-Khoutorsky, P. Séguéla, A. Ribeiro-da-Silva, A. Binshtok, A. Khoutorsky. (2022). mTORC2 mediates structural plasticity in distal nociceptive endings that contributes to pain hypersensitivity following inflammation. Journal of Clinical Investigation, May 17:e152635.
Tansley, S., S. Uttam, A. Ureña Guzmán, M. Yaqubi, A. Pacis, M. Parisien, O. Rabau, L. Haglund, J. Ouellet, Santaguida, J. Ragoussis, J. Zhang, M. W. Salter, L. Diatchenko, L. M. Healy, J. S. Mogil and A. Khoutorsky. (2022). Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain. Nature Communication. 2022 Feb 11;13(1):843.
Roque PS, Thörn Perez C, Hooshmandi M, Wong C, Eslamizade MJ, Heshmati S, Brown N, Sharma V, Lister KC, Goyon VM, Neagu-Lund L, Shen C, Daccache N, Sato H, Sato T, Mogil JS, Nader K, Gkogkas CG, Iordanova MD, Prager-Khoutorsky M, McBride HM, Lacaille JC, Wykes L, Schricker T, and Khoutorsky. (2022). Parvalbumin interneuron loss mediates repeated anesthesia-induced memory deficits. Journal of Clinical Investigation, doi: 10.1172/JCI159344.
Hooshmandi, M, Truong, T, Fields, E, Thomas, RE, Wong, C, Sharma, V, Gantois, I, Soriano Roque, P, Chalkiadaki, K, Wu, N, Chakraborty, A, Tahmasebi, S, Prager-Khoutorsky, M, Sonenberg, N, Suvrathan, A, Watt, AJ, Gkogkas, CG and Khoutorsky. (2021). 4E-BP2-dependent translation in cerebellar Purkinje cells controls spatial memory but not autistic-like behaviours. Cell Reports, Apr 27;35(4):109036. doi: 10.1016/j.celrep.2021.109036.