IRCM Researchers

Mechanisms of asymmetric cell division
The ability of stem cells to generate two daughter cells of different types is essential for the production of cell diversity and tissue function. When cellular and molecular mechanisms governing this process, called asymmetric cell division, are altered, various developmental malformations or diseases can arise. In order to better understand the contribution of asymmetric cell divisions in the development of pathologies, we are studying the fundamental mechanisms that precisely regulate the production of asymmetric divisions. More specifically, we are working to understand how stem cells orient their mitotic spindle so as to unevenly distribute certain proteins or mRNAs in daughter cells in order to influence their fate differently.

Direct neuronal reprogramming
The use of stem cells to regenerate various tissues following degenerative diseases or injury has gained a lot of attention in recent years. As stem cells are multipotent, they can be differentiated into any cell type of interest, which can then be grafted to reconstitute a given cell population. However, this approach is facing different challenges, especially in the nervous system, where the efficiency of transplantation and the level of integration of transplanted cells into neural circuits is low. To get around this problem, we are working to identify approaches to directly reprogram glial cells of nervous tissue into neurons. We have developed a method that allows us to screen a large number of parameters to identify the conditions for converting glial cells into neurons in situ. This approach avoids complex cell transplantation surgeries and takes advantage of the presence of glial cells already integrated into the nervous system to replace neurons lost in various neurodegenerative diseases.

Control of cell polarity 
The functional organization of different tissues depends on the ability of the cells that constitute them to precisely localize molecules or organelles asymmetrically. Cells then use this information to orient themselves in space and control various physiological functions. Some projects in our laboratory aim to better understand the molecular mechanisms governing the production of cell polarity and its role in the development and function of nervous tissues, in particular the retina.

Temporal patterning in neural development
During development of the nervous system, neural stem cells produce different cell types at specific times. This temporal patterning is critical to the production of a functioning nervous system, guiding the formation of neural circuits that control our movements, perception, learning and emotions. The production of cells at the wrong time of development can have serious consequences such as malformation of the neural tube (spina bifida), cognitive delays, and perception problems. Some of our work therefore aims to identify the molecular mechanisms allowing the production of the right cell type at the right time. More specifically, we use genomic approaches to identify the genetic networks involved in these decisions, with particular emphasis in identifying transcription factors that allow neural stem cells to change their temporal identity as development proceeds.

Genetic and molecular bases of retinal degenerative diseases
Inherited retinal degenerations cause the death of photoreceptors, the highly specialized cells in the retina that convert light into nervous signals. These diseases remain incurable and can lead to blindness. Thus, the identification of genetic mutations causing retinal degeneration is essential for the development of therapeutic approaches such as gene therapy. Identifying the disease-causing mutations is an important first step, but how these mutations precisely lead to photoreceptor cell death is often not understood, hampering therapeutic development efforts. To overcome this problem, we are collaborating with clinical geneticists who identify genetic mutations associated with retinal degenerations and model the disease in mice to elucidate how the mutations affect photoreceptor survival.

Protein homeostasis and neuroprotection
Several neurodegenerative diseases are caused by the accumulation of toxic proteins in neurons. These findings suggest that understanding how these proteins accumulate in cells could help design ways to lower their levels, which could have a beneficial effect on disease progression. Some projects in the lab try to identify the cellular and molecular mechanisms controlling homeostasis of these disease-associated proteins and to use this knowledge to develop methods to reduce the levels of these proteins in diseased neurons.