In the recent years, work of many researchers throughout the world demonstrated that the immune system plays a critical role in maintaining CNS homeostasis during healthy state and disease. Neuroinflammation emerged as a common denominator in many neurodegenerative diseases including multiple sclerosis, Parkinson’s diseases, Alzheimer’s diseases, amyotopic later sclerosis, Huntigton’s diseases, epilepsy, stroke, etc. I truly believe that lessons learnt from one neurodegenerative disease can be applied to study mechanisms of several other neurodegenerative diseases. My goal is to find key players that regulate neuroinflammatory responses and to use this knowledge in designing novel therapies to treat neurodegenerative diseases.
Astrocytes and microglia:
Development of an autoimmune disorder requires hyperactivation and proliferation of autoreactive lymphocytes and, at the same time, it requires an increase in vulnerability of the target tissue. In case of MS, all people have autoreactive T-cells, but only those susceptible to neuro-inflammation develop the disease. The exact mechanism of this susceptibility is unknown. Astrocytes and microglia are the major contributors to inflammation and cytotoxicity, which are associated with the developing of neurodegenerative diseases. Astrocytes and microglia play an important role in maintaining homeostasis of the CNS by clearing cellular debris, secreting growth factors, maintaining blood brain barrier and reuptake of neurotransmitters. Misregulation of any of these functions can provoke molecular mechanisms that will lead to the increased inflammation and thus compromise homeostasis of CNS.
Novel family of proteins:
A recently discovered family of proteins, Nlrs, are among main regulatory proteins of the immune system. Nlr family of proteins comprises 23 members in human and 34 in mice and can regulate both innate and adaptive immune system. Up on pathogen recognition, these proteins can activate multiple pro-inflammatory molecular pathways including formation of inflammasome and activation of NFkB and MAP kinase pathways. Nlrs have been implicated in development of autoimmune disorders; however, their function in neuroinflammation and neurodegeneration is poorly understood.
The long term objective of Gris Lab of Neuroimmunology is to study the role of Nlrs in neuroinflammation. Currently two proteins are under investigation: Nlrx1 and Nlrp12. Both proteins have been implicated to interfere with NFkB pathway.
Tools we use:
We conduct multi-colour (9 colour) experiments and use phosophoflow combined with bar coding. We also perform intracellular cytokine staining. We use state of the art Flow cytometers: BD FACS Aria III and BD FACS Canto.
We use cell lines of mouse and human microglia, astrocytes, and neurons. Also, we use primary mouse cell culture. We look at the function of immune system including the function of T cells, microphages, neurtophil, and antigen presenting cell function.
We use transgenic mice deficient in different NLR proteins to study the mechanisms of human diseases. For our details on ethics please Read here.
We use regular epifluorescence and confocal microscopy to study the expression of NLR proteins and to study pathophysiology of neurodegenerative diseases.
Microfluidics and live cell imaging
Currently, in collaboration with Dr. Juncker, form McGill university, we are developing a model of focal ischemia in brain slices using nanotechnology based microfluidics probes.
We use other more conventional tools in cellular and molecular biology such as Western blotting, immunohistochemistry, RNA quantification, etc.