Jasna Kriz, Ph.D., M.D.
Professor, Department of Psychiatry and Neurosciences, Faculty of Medecine, Université Laval
Innovative approaches to understand the role of immune cells in brain diseases
Dr. Jasna Kriz studies the role of brain immune cells, called microglia, in the healthy brain, in cerebral ischemia, and in neurodegenerative diseases such as amyotrophic lateral sclerosis.
Dr. Kriz has developed mouse models in which she can detect the activation of genes of interest by bioluminescence, and thus see which genes are activated or inhibited during brain damage, or in neurodegenerative diseases. These models make it possible to see the expression of genes in real time and in living mice, with great precision.
These mice represent a powerful tool for analysis to understand the evolution of the disease in living animals. They are also used to test drugs to see their potential to block or slow down the effects of brain damage and neurodegenerative diseases.
Dr. Kriz's research has led to a better understanding of the immune response in amyotrophic lateral sclerosis and frontotemporal dementia and cerebral ischemia, as well as sepsis and ischemia in neonates.
Her team is also involved in clinical and preclinical studies with a class of molecules, withanolides, which, when administered early, have increased the lifespan of mouse models of amyotrophic lateral sclerosis.
Dr. Kriz’s initial research program focuses on the biology and pathology of glial cells in the acute brain injuries as well as in the models of chronic neurological disorders.
Over the past years in Dr Kriz developed and validated series of mouse models of bioluminescence and fluorescence allowing the non-invasive and time-lapse imaging of processes associated with brain injuries and repair including inflammation, neuronal damage and regeneration. The strategy was to generate transgenic mice expressing dual reporters, the firefly luciferase (Fluc) and the green fluorescence reporter GFP, whose transcription is dependent upon the selected gene promoter. The Fluc bioluminescence is measured and quantified in living intact animals by using high sensitivity/high resolution cooled charged-coupled device (CCD) camera whereas high resolution fluorescence imaging can be done with microscopes equipped with two-photon laser scanning capabilities. These mice represent a novel powerful analytical tool for understanding in vivo pathology of chronic neurological disorders as well as for evaluating pharmacokinetics and longitudinal responses to drug therapies.
Our initial studies suggest that biophotonic signals imaged from the live animals can be used as valid biomarkers to screen for novel biocompatible molecules and/or to visualize distinct pathological events in brain injuries and in chronic neurological disorders such as amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia. More recently to link real-time cellular imaging phenotypes with distinct molecular signatures Dr Kriz also developed novel model-systems for in –vivo cell type specific molecular profiling of neurons and microglial cells.
The following projects are currently active in the laboratory:
- The role of innate immune response and microglial cells in neonatal brain injuries
- Galectin-3 as endogenous immunomodulatory molecule • Glia- neuron crosstalk in ALS pathogenesis
- Preclinical and clinical studies with withanolides: Therapeutic effects, molecular signatures and biomarkers
- Canadian Consortium of Neurodegeneration and Aging (Team#2 Inflammation and Trophic Factor Deregulation
Yuan Cheng Weng, Research Assistant
Hejer Boutej, Postdoc
Louis-Charles Béland, PhD student
Reza Rahimian, PhD student
Sai Sampath Thammisetty, PhD student
Senthil Krishnasamy, Phd student
- Gravel M, Béland LC, Soucy G, Abdelhamid E, Rahimian R, Gravel C, Kriz J (2016). IL-10 Controls Early Microglial Phenotypes and Disease Onset in ALS Caused by Misfolded Superoxide Dismutase, J Neurosci. 2016 Jan 20;36(3):1031-48
- Cordeau P Jr, Lalancette-Hébert M, Weng YC, Kriz J (2016). Estrogen receptors alpha mediates postischemic inflammation in chronically estrogen-deprived mice Neurobiol Aging. 2016 Apr;40:50-60
- Patel P, Julien JP, Kriz J. (2015) Early-stage treatment with withaferin a reduces levels of misfolded superoxide dismutase 1 and extends lifespan in a mouse model of amyotrophic lateral sclerosis. Neurotherapeutics. 2015 Jan;12(1):217-33
- Lalancette-Hébert M, Swarup V, Beaulieu JM, Bohacek I, Abdelhamid E, Weng YC, Sato S, Kriz J. (2012) Galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury. J Neurosci. 2012 Jul 25;32(30):10383-95
- Swarup V, Phaneuf D, Bareil C, Roberston J, Kriz J*, Julien JP*(2011). Pathological hallmarks of ALS/FTLD in transgenic mice produced with genomic fragments encoding wild-type or mutant forms of human TDP-43. Brain Pt 9:2610 * co-corresponding author
- Lalancette–Hébert M, Julien C, Cordeau P, Bohacek I , Weng YC, Calon F, Kriz J (2011). Accumulation of Dietary DHA in the Brain Attenuates Acute Immune Response and Development of Post-ischemic Neuronal Damage. Stroke 10:2903
- Lalancette-Hébert, M., Phaneuf, D., Soucy, G., Weng, Y.C. and Kriz*, J. (2009) Live imaging of Toll-like receptor 2 response in cerebral ischaemia reveals a role of olfactory bulb microglia as modulators of inflammation. Brain 132:940-54.
- Keller F,*Gravel M*, Kriz J (2009). Live imaging of ALS: Marked induction of GFAP in Schwann cells determines disease onset. Glia
- Lalancette-Hébert M, Gowing G, Simard A, Weng YC and Kriz J *(2007) Selective ablation of proliferating microglia exacerbates ischemic injury in brain. J. Neurosci. 27, 2596-2605
- Maysinger, D, Behrendt M, Lalancette-Hébert M, Kriz J (2007). Real time imaging of astrocyte response to quantum dots: In vivo screening model system for biocompatibility of nanoparticles. Nano Lett. 7, 2513-20.
Dr. Jasna Kriz obtained her MD and PhD in Biomedicine & Health from University of Rijeka, Croatia followed by postdoctoral training at the Centre for Research in Neuroscience of McGill University, Montreal, Canada (1999-2003). 2004 she was recruited at Laval University, Quebec City, Canada where she presently holds a title of Professor at the Department of Psychiatry and Neuroscience, Faculty of Medicine Laval University. At 2006 she received prestigious R&D/HRF/CIHR (Canadian Institutes for Health Research) Career Award (Project entitled: Brain inflammatory response as a therapeutic target in cerebral ischemia). Her studies, using a transgenic model for selective ablation of proliferating microglial cells provided one of the first in vivo evidence of the neuroprotective potential of microglial cells in brain ischemia. Moreover, to study inflammation and brain recovery from living animals and in real time she developed series of novel biophotonic (bioluminescence and fluorescence) transgenic models for in vivo analysis of microglial activation/innate immune response, astrogliosis as well as brain recovery. These novel model-systems represent a powerful analytical tool for evaluating biocompatibility and pharmacokinetics of novel molecules as well as longitudinal responses to drug therapies. Moreover, recent studies from her laboratory showed that the biophotonic mouse models may serve to generate new knowledge in in vivo pathology and in development of immunomodulatory therapeutic strategies in acute in chronic neurodegenerative disorders.
FRSQ (Fonds de recherché en santé) Senior Scholar (12/2011-12/2015)
R&D/Health Research Foundation/CIHR, Career Award (07/2006-12/2011)
FRSQ (Fonds de recherché en santé) Junior Scholar (07/2004-07/2007)
2601 Chemin de la Canardière Québec (Québec) G1J 2G3 Canada
