Shalina Ousman Lab
Multiple sclerosis
Multiple sclerosis (MS) is an autoimmune disease leading to central nervous system (CNS) degeneration in approximately 2.7 million people worldwide. Current therapies for MS are useful in some patients but they do not prevent progression of the disease and are ineffective in many patients thus underscoring a vital need for new therapies. My research interest is to (a) identify endogenous protective molecules and/or mechanisms in MS that suppress autoimmunity and CNS damage, (b) define their underlying cellular and molecular processes, and (c) mobilize the beneficial functions of the protective mechanism(s) to prevent the progression of MS.
Numerous molecules are up-regulated or down-regulated in the brains of people with MS. We are investigating the role of two such factors, alphaB-crystallin (αBC) and Cystatin C, in remyelination and astrocyte biology. We are also in interested in deciphering the mechanisms underlying progression in MS. To that end, we are studying autophagy and the gut microbiome.
Peripheral nerve regeneration
Injury to the axons of peripheral nervous system (PNS) neurons from adult mammals generally results in regeneration of nerve fibers back to their target. In humans however, PNS axon regrowth is limited and this has been attributed in part to deterioration of the supportive environment that is primarily mediated by Schwann cells (SCs). SCs benefit damaged peripheral neurons by 1) secreting neurotrophic factors to maintain cell survival until re-contact with their target, 2) producing adhesion molecules that provide a substrate for axon elongation, 3) phagocytosing myelin associated axon growth inhibitors and, 4) remyelinating regenerating axons. In humans however, these positive functions of SCs are truncated when these glial cells are denervated for a significant amount of time as occurs when the injury is severe such as a transection as compared to a crush damage, the greater the distance of the injury site from the target and, the older and unhealthier the individual. Our lab is interested in understanding the molecular signals that control the beneficial functions of SCs following peripheral nerve injury so as to enhance and prolong the growth promoting state of these glial cells until regenerating axons regain contact with their targets.
Publications
Peer reviewed papers (trainees underlined, #corresponding author)
Umansky D, Hagen KM, Chu TH, Pathiyil RK, Alzahrani S, Ousman SS and Midha R (2022) Functional Gait Assessment Using Manual, Semi-automated and Deep Learning Approaches Following Standardized Models of Peripheral Nerve Injury in Mice. Biomolecules.
Hagen KM and Ousman SS# (2021) Aging and the Immune Response in Diabetic Peripheral Neuropathy. Journal of Neuroimmunology 355(577574): 1-13. (review)
Lim EM, Hoghooghi V, Hagen KM, Kapoor K, Frederick A, Finlay TM and Ousman SS# (2021) Presence and activation of pro-inflammatory macrophages is associated with CRYAB expression in vitro and after peripheral nerve injury. Journal of Neuroinflammation 18(82): 1-16.
Hagen KM and Ousman SS# (2021) The Immune Response and Aging in Chronic Inflammatory Demyelinating Polyradiculoneuropathy. Journal of Neuroinflammation 18(78): 1-18. (review)
Hagen KM and Ousman SS# (2021) The Neuroimmunology of Guillain-Barré Syndrome and the Potential Role of an Aging Immune System. Frontiers in Aging Neuroscience 12(613628): 1-19. (review)
Hoghooghi V, Palmer AL, Frederick A, Jiang Y, Merkens JE, Balakrishnan A, Finlay TM, Grubb A, Levy E, Gordon P, Jirik FR, Nguyen MD, Schuurmans C, Visser F, Dunn SE and Ousman SS# (2020) Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis. Cell Reports 33(108236): 1-24.
Palmer AL and Ousman SS# (2018) Astrocytes and Aging. Frontiers in Aging Neuroscience 10(337): 1-14. (review)
Rothbard JB, Kurnellas MP, Ousman SS, Brownell S, Rothbard JJ and Lawrence Steinman L (2018) Small Heat Shock Proteins, Amyloid Fibrils and Nicotine Stimulate a Common Immune Suppressive Pathway with Implications For Future Therapies. Cold Spring Harbor Perspectives in Medicine 9(a034223): 1-15.
Caprariello AV, Rogers JA, Morgan ML, Hoghooghi V, Plemel JR, Koebel A, Tsutsui S, Dunn JF, Kotra LP, Ousman SS, Yong VW and Stys PK (2018) Biochemically-altered myelin triggers autoimmune demyelination. Proceedings of the National Academy of Sciences USA 115(21):5528-5533.
Finlay TM, Palmer AL and Ousman SS# (2018) Murine neutrophils treated with alphaB-crystallin reduce IL-12p40 production by dendritic cells. Immunology 155: 72-84.
Ousman SS#, Frederick A and Lim EMF (2017) Chaperone proteins in the central nervous system and peripheral nervous system after nerve injury. Frontiers in Neuroscience 11(79): 1-10. (Invited review)
Lim EMF, Musa A, Frederick A and Ousman SS# (2017) AlphaB-crystallin expression correlates with aging deficits in the peripheral nervous system. Neurobiology of Aging 53: 138-149.
Lim EMF, Nakanishi ST, Hoghooghi V, Eaton SEA, Palmer AL, Frederick A, Stratton JA, Stykel MG, Whelan PJ, Zochodne DM, Biernaskie J and Ousman SS# (2017) AlphaB-crystallin regulates remyelination following peripheral nerve injury. Proceedings of the National Academy of Sciences USA 114(9): E1707-E1716.
Scott BNV, Roberts DJ, Robertson HL, Kramer AH, Lauplan KB, Ousman SS, Kubes P and Zygun D (2013) Incidence, prevalence, and occurrence rate of infection among adults hospitalized after traumatic brain injury: study protocol for a systematic review and meta-analysis. Systematic Reviews 2(68): 66-74.
Acharjee S, Nayani N, Tsutsui M, Hill MN, Ousman SS and Pittman QJ (2013) Altered cognitive-emotional behavior in early experimental autoimmune encephalitis - cytokine and hormonal correlates. Brain Behavior and Immunity 33: 164-72.
Quach QL, Metz LM, Thomas JC, Rothbard JB, Steinman L and Ousman SS# (2013) CRYAB modulates the activation of CD4+ T cells from relapsing-remitting multiple sclerosis patients. Multiple Sclerosis Journal 19(14):1867-1877.
Oyebamiji AI, Finlay TM, Hough RM, Hoghooghi V, Lim EM, Wong CHY and Ousman SS# (2013) Characterization of migration parameters on peripheral and central nervous system T cells following treatment of experimental allergic encephalomyelitis with CRYAB. Journal of Neuroimmunology 259(1-2):66-74.
Steinman L, Axtell RC, Barbieri D, Bhat R, Brownell SE, de Jong BA, Dunn SE, Grant JL, Han MH, Ho PP, Kuipers HF, Kurnellas MP, Ousman SS and Rothbard JB (2013) Piet Mondrian's trees and the evolution in understanding multiple sclerosis, Charcot Prize Lecture 2011. Multiple Sclerosis Journal 19(1):5-14.
Kurnellas MP, Brownell S, Su L, Leon S, Malkovskiy AV, Rajadas J, Dolganov G, Chopra S, Schoolnik GK, Sobel RA, Webster J, Ousman SS, Becker RA, Steinman L and Rothbard JB (2012) Chaperone activity of small heat shock proteins underlies therapeutic efficacy in experimental autoimmune encephalomyelitis. Journal of Biological Chemistry 287(43):36423-34.
Ousman SS# and Kubes P# (2012) Immune surveillance in the central nervous system. Nature Neuroscience 15(8):1096-1101 (Invited review)
Pangratz-Fuehrer S, Kaur K, Ousman SS, Steinman L and Liao YP (2011). Functional rescue of experimental ischemic optic neuropathy with B-crystallin. Eye 25(6): 809-817.
deLuca LS, Pikor N, O’Leary N, Galicia-Rosas G, Ward LA, Defreitas D, Finlay TM, Ousman SS, Osborne LR and Gommerman JL (2010) Substrain differences reveal novel disease-modifying gene candidates that alter the clinical course of a rodent model of multiple sclerosis. Journal of Immunology 184(6):3174-85.
Hung J, Chansard M, Ousman SS, Nguyen MD and Colicos MA (2010) Activation of microglia by neuronal activity: results from a new in vitro paradigm based on neuronal-silicon interfacing technology. Brain Behavior Immunity 24(1):31-40.
Han MH, Hwang S-I, Roy DB, Lundgren DH, Price JV, Ousman SS, Fernald GH, Gerlitz B, Robinson WH, Baranzini SE, Grinnell BW, Raine CS, Sobel RA, Han DK and Steinman L (2008) Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature 451 (7182):1076-81.
Ousman SS, Tomooka BH, van Noort JM, Wawrousek EF, O’Conner K, Hafler DA, Sobel RA, Robinson WH and Steinman L (2007) Protective and therapeutic role for alphaB-crystallin in autoimmune demyelination. Nature 448 (7152): 474-479.
Dunn SE*, Ousman SS*, Sobel R, Zuniga L, Crowell A, Loh J and Steinman L (2007) Peroxisome proliferator-activated receptor (PPAR)-alpha expression in T cells mediates gender differences in development of T cell-mediated autoimmunity. Journal of Experimental Medicine 204(2): 321-330. *Co-first authors
Wacher C, Müller M, Markus HJ, Getts DR, Zabaras R, Ousman SS, Terenzi F, Sen GC, King NJC and Campbell IL (2006) Coordinated regulation and widespread cellular expression of the interferon stimulated genes (ISG)-49, ISG-54 and ISG-56 in the central nervous system after infection with distinct viruses. Journal of Virology 81(2):860-71. (Impact factor=5.076)
Ousman SS, Wang JP and Campbell IL (2005) Differential regulation of interferon regulatory factor (IRF)-7 and IRF-9 gene expression in the central nervous system during LCMV viral infection. Journal of Virology 79(12):7514-27.
Ousman SS and Campbell IL (2005) Regulation of murine interferon regulatory factor gene expression in the central nervous system determined by multiprobe RNase protection assay. In: Methods in Molecular Medicine: Interferon Methods and Protocols, Humana Press Inc., Totowa, NJ. Ed. Carr, Daniel J. J. Vol. 116 p. 115-134. (Invited book chapter)
David S and Ousman SS (2002) Recruiting the immune response to promote axon regeneration in the injured spinal cord. The Neuroscientist 8(1): 33-41. (Invited review)
David S and Ousman S (2002) Stimulating immune system – central nervous system interaction to promote long distance axon regeneration. In: Glial Interfaces in the Nervous System, Hakan Aldskogius and John Frahar (eds), IOS Press, Amsterdam, Netherlands, 2002, pp 153-164. (Invited book chapter)
Ousman SS and David S (2001) MIP-1alpha, MCP-1, GM-CSF, and TNF control the immune response mediates rapid phagocytosis of myelin from the adult mouse spinal cord. Journal of Neuroscience 21(13):4649-4656.
Ousman SS and David S (2000) Lysophosphatidylcholine induces rapid recruitment and activation of macrophages in the adult mouse spinal cord. GLIA 30 (1): 92-104.
Issued patents
Steinman L, Ousman SS and Robinson WH. Alpha B-crystallin as a therapy for multiple sclerosis. Stanford University Office of Technology Transfer, Stanford, CA, USA. US Patent No. 8,835,391; filed May 29, 2000, Issued September 16, 2014.
Steinman L, Ousman SS and Robinson WH. Alpha B-crystallin as a therapy for ischemia or inflammation. Stanford University Office of Technology Transfer, Stanford, CA, USA. US Patent No. 8,771,689; filed June 23, 2011, Issued July 8, 2014.
Steinman L, Ousman SS and Robinson WH. Alpha B-crystallin as a therapy for autoimmune demyelination. Stanford University Office of Technology Transfer, Stanford, CA, USA. Israeli Patent No. 199223; Issued April 30, 2013.
Steinman L, Ousman SS and Robinson WH. AlphaB-crystallin as a therapy for rheumatoid arthritis. Stanford University Office of Technology Transfer, Stanford, CA, USA. US Patent No. 7,875,589; filed December 11, 2007, Issued January 25, 2011, Licensed to Cardinal Therapeutics.
Funding
OPERATING GRANTS
CIHR
Oct 1, 2020-Sept 30, 2025: Operating Grant, Canadian Institutes of Health Research (The injured peripheral nervous system and aging; Principal Investigator)
Oct 1, 2019-Sept 30, 2020: Bridge Funding, Canadian Institutes of Health Research (Aging and the injured peripheral nervous system; Principal Investigator)
Oct 1, 2014-Sept 30, 2019: Operating grant, Canadian Institutes of Health Research (Investigating the role of Cystatin C in multiple sclerosis; Principal Investigator)
Oct 1, 2009-Sept 30, 2014: Operating Grant, Canadian Institutes of Health Research (Mechanisms underlying alphaB-crystallin function in multiple sclerosis; Principal Investigator)
MS Canada
Apr 1, 2017-Mar 31, 2020: Operating Grant, Multiple Sclerosis Society of Canada (Elucidating the role and regulation of astrocytes in multiple sclerosis; Principal Investigator)
Apr 1, 2014-Mar 31, 2017: Operating grant, Multiple Sclerosis Society of Canada,(Investigating the role of Cystatin C in multiple sclerosis; Principal Investigator)
Jul 1, 2012-Jun 30, 2015: Salary Award, Dr. Donald Paty Career Development Award, Multiple Sclerosis Society of Canada
Jul 1, 2009-Jun 30, 2012: Salary Award, Dr. Donald Paty Career Development Award, Multiple Sclerosis Society of Canada
AHFMR
Jul 2009-Jun 2016: Salary Award, AHFMR Scholar, Alberta Heritage Foundation for Medical Research
Jul 1, 2009-Jun 30, 2016: Research Allowance, Alberta Heritage Foundation for Medical Research (Function of alphaB-crystallin in multiple sclerosis; Principal Investigator)
Jul 1, 2009-Jun 30, 2015: Investigator Incentive Award (Operating) (for holding dual salary awards), Alberta Heritage Foundation for Medical Research (Function of alphaB crystallin in multiple sclerosis; Principal Investigator).
Jul 1, 2009-Jun 30, 2012: Establishment Grant, Alberta Heritage Foundation for Medical Research (Function of alphaB-crystallin in multiple sclerosis; Principal Investigator)
CFI
Mar 1, 2010-Mar 31 2013: Equipment grant, Canada Foundation for Innovation Leaders Opportunity Fund and Government of Alberta Advanced Education and Technology Small equipment grant program, Project # 22137 (Establishment of microscopy and real-time quantitative PCR infrastructure to investigate neurodegenerative disorders; Co-PI with Dr. Roger Thompson)
UCalgary
Apr 1, 2019-Mar 31, 2020: Operating Grant, Alberta Multiple Sclerosis Collaboration Translation, Commercialization and Implementation Competition (Targeting Cystatin C with Valsartan as a treatment for multiple sclerosis; Principal Investigator)
Apr 1, 2019-Mar 31, 2021: Pilot Grant (Operating), HBI MS NeuroTeam Pilot Grant (The Role of Autophagy in the Transition to Progressive Multiple Sclerosis; Principal Investigator, Co-PI: Dr. Jodie Burton)
Apr 1, 2019-Mar 31, 2020: Bridge Funding (Operating), Calgary Cumming School of Medicine Bridge Funding Program (Aging and the injured peripheral nervous system; Principal Investigator)
Nov 2018-Oct 2019: High Risk High Reward Grant (Operating), Hotchkiss Brain Institute (Astrocytes and CD4+ T cells during autoimmune demyelination; Principal Investigator)
Jan 1, 2018-Jun 30, 2019: Seed Grant (Operating), Project # 1045929, University Research Grants Committee, University of Calgary (Aging and the injured peripheral nervous system; Principal Investigator)
Apr 1, 2018-Mar 31, 2019: Bridge Funding (Operating), Calgary Cumming School of Medicine Bridge Funding Program (Aging and the injured peripheral nervous system; Principal Investigator)
Aug 2014-Jul 2015: Bridge Funding (Operating), AIHS Sustainability Funding program and University of Calgary Cumming School of Medicine Bridge Funding program (Mechanisms underlying regeneration of the injured peripheral nervous system; Principal Investigator)
Oct 30, 2012-Dec 31, 2013: Seed Grant (Operating), University Research Grants Committee, University of Calgary (The alphaB-crystallin of peripheral nerve regeneration; Principal Investigator).
TRAINEE AWARDS
Ruiqi Wang
2023: MS Canada Trainee Scientific Conference Travel Award
2023-2025: HBI International Graduate Recruitment Scholarship – PhD
Yohan Zonta
2022-2026: Multiple Sclerosis Society of Canada Doctoral Studentship
2022-2024: Harley N. Hotchkiss Doctoral Scholarship in Neuroscience
Megan Krysak
2021: Alberta MS Network Summer Studentship
Zachary Bailey
2020: Alberta Graduate Excellence Scholarship
Kathleen Hagen
2022: Canadian Association for Neuroscience Travel Award
2022: Keith Sharkey Graduate Travel Award
2022: First Place, 17th Annual Hotchkiss Brain Institute Research Day Poster Competition
2022: Second Prize in Hotchkiss Brain Institute Advanced Microscopy Platform Striking Image Competition
2020: Spinal Cord Nerve Injury & Pain NeuroTeam Studentship
2021: Society for Neuroscience Trainee Professional Development Award
Matthew Joel
2018: University of Calgary Queen Elizabeth II Scholarship
2018: Spinal Cord Nerve Injury & Pain NeuroTeam Studentship
Sophie Gobeil
2017: Alberta Innovates Summer Research Studentship
2017: Alberta MS Network Summer Studentship (declined)
Kaylyn Kubes
2020: Alberta MS Network Summer Studentship
2019: Alberta Innovates Summer Research Studentship
2018: Program for Undergraduate Research Experience Studentship (declined)
2018: Alberta MS Network Summer Studentship
2017: Alberta Innovates Summer Research Studentship
2017: Alberta MS Network Summer Studentship (declined)
Ronald Tran
2017: Faculty of Science/Hotchkiss Brain Institute Summer Research Studentship
Alexandra Palmer
2019: William H. Davies Medical Research Scholarship
2018: Alberta MS Network Travel Award
2018: Canada Neuroimmunology Knowledge Dissemination Award
2018: Hotchkiss Brain Institute Conference Travel Award
2016: MDNS GSE MTF Funds for Conference/Travel
2016: Alberta MS Network Travel Award
2015: Achievers in Medical Science Graduate Recruitment Scholarship
Vahid Hoghooghi
2018: Canada Neuroimmunology Knowledge Dissemination Award
2016: MDNS GSE MTF Funds for Conference/Travel
2015: MDNS GSE MTF Funds for Conference/Travel
2014: Graduate Studies Travel Award
2013-2017: Multiple Sclerosis Society of Canada Doctoral Studentship
2012: University of Calgary Queen Elizabeth II Scholarship
Marshal Wolff
2012: University of Calgary BSc Neuroscience Program Summer Research Scholarship
Erin-Mai Lim
2015: MDNS GSE MTF Funds for Conference/Travel
2012: Graduate Studies Travel Award
2012: Arun Anbazhagan HBI Travel Award
2011-2016: Alberta Innovates-Health Solutions Graduate Studentship
2011: University of Calgary Queen Elizabeth II Scholarship
2011: HBI Spinal Cord and Nerve Injury Program Scholarship
Trisha Finlay
2012: Graduate Studies Travel Award
2012: International Society for Neuroimmunology Travel Award
2011-2014: CIHR Vanier Canada Graduate Scholarship
2010-2015: Alberta Innovates-Health Solutions Graduate Studentship
2010: Multiple Sclerosis Society of Canada Doctoral Studentship
2010: HBI Dr. T. Chen Fong Scholarship in Neuroscience
Omid Javizian
2011: Multiple Sclerosis Society of Canada Summer Studentship
Jenna Thomas
2010: Multiple Sclerosis Society of Canada Summer Studentship
Rachael Hough
2010: Alberta Innovates-Health Solutions Summer Studentship
2009: Summer Work Employment Experience Program Studentship
Shalina S. Ousman, PhD. Associate Professor
Associate Professor (2015-present), University of Calgary (Clinical Neurosciences; Cell Biology & Anatomy)
Assistant Professor (2008-2015), University of Calgary (Clinical Neurosciences; Cell Biology & Anatomy)
PDF (2004-2008), Stanford University (Neurology & Neurological Sciences)
PDF (2001-2004), The Scripps Research Institute (Neuropharmacology)
PhD (1995-2001), McGill University (Neurology and Neurosurgery)
MSc (1993-1995), Queen’s University (Physiology)
BScH (1989-1993), Queen’s University (Biology)