Research Interests

Signaling between neurons and glia (the non-neuronal cells of the brain), as well as between glial cells themselves, is critical for the maintenance of brain homeostasis, yet very little is known about this process under physiological conditions.  One of the main focuses of our laboratory is to identify novel intercellular signaling molecules and mediators in the brain and studying their physiological roles.  Our current research shows that mitochondrial transcription factor A (Tfam), which normally resides inside the cells, can be released into the extracellular space by stimulated and dying cells.  Once released extracellularly, Tfam can be recognized by specific receptors on glial cell membranes and can trigger their physiological responses.

In addition to Tfam, microparticles are released from resting, activated and dying cells and could be used as a means of intercellular signaling to communicate the functional status of the donor cell to the surrounding target cells without direct cell-to-cell contact.  Microparticles are small (0.1-1 mm) vesicles that are formed by outward blebbing of cellular membrane.  They may contain phospholipids, DNA, RNA and both membrane-bound and cytoplasmic proteins of the donor cell.  Microparticle functions have been characterized extensively in peripheral tissues, but only recently have their roles in the central nervous system physiology emerged.  It has been reported that most types of brain cells can shed microparticles, which contribute to intercellular communication during neuronal development, synaptic activity and nerve regeneration.  The composition of microparticles could vary depending on the activation status of the donor cells.  Therefore, both Tfam and microparticles could be critical for transmitting information about the functional status of surrounding cells to glia. 

Our research goal is to identify the receptors and intracellular signaling pathways mediating the effects of extracellular Tfam as well as microparticles originating from different types of brain cells under different conditions.  This information is critical not only for our understanding of the mechanisms governing homeostasis of the central nervous system, but it could also lead to identification of novel molecular targets that could be used to manipulate the functional responses of glial cells. 

An increasing body of evidence indicates that glial cell activation is part of a series of physiological events, but it can also contribute to various central nervous system pathologies, such as stroke, trauma and neurodegenerative disorders including Alzheimer’s disease.  Therefore, an additional focus of our laboratory is identification of novel drugs and natural compounds that could be used to modify glial functions.  In the past, we have performed studies with bioactive compounds extracted from plants and bacteria, as well as novel chemical compounds synthesized by our collaborators from UBC Okanagan and internationally.  Our current focus are metal-containing compound; we have demonstrated that select organo-metallo compounds can inhibit harmful activation of glial cells and protect neurons from glial toxins.  We are currently studying a series of new derivatives of the most active compounds in order to improve their activity as glial cell inhibitors.  In a parallel collaborative effort, we are developing a novel class of organo-metallo compounds which target several different cellular and biochemical mechanisms believed to play key roles in the pathogenesis of Alzheimer’s disease.

"Your theory is crazy, but it's not crazy enough to be true."
- Niels Bohr
"The saddest aspect of life right now is that science gathers knowledge faster than society gathers wisdom."
- Isaac Asimov