Current Projects

Peripheral Nerve Regeneration and Aging

It is accepted that the aging process significantly impairs the ability of peripheral nerves to regenerate after injury – but the molecular pathways that prevent efficient repair remain unknown. Peripheral nerves are mainly composed of axonal processes from neurons and Schwann cells; together they build an interactive and functional unit. These peripheral nerves, which must be maintained throughout adult life, are renowned for their remarkable ability to regenerate. Regeneration requires axonal regrowth, in tandem with activation of a regenerative program by resident Schwann cells. Injury prompts Schwann cells to dedifferentiate, thus becoming "repair cells", which can then switch back to be differentiated remyelinating cells. Current thinking is that imbalances in this tightly regulated system result in age-related decline in nerve maintenance and regeneration as well as in hyper-proliferative disorders such as cancer.

In her laboratory Morrison and her team are engaged in a number of projects related to the peripheral nervous system (PNS). These include

• investigating the plasticity of the Schwann cell differentiation state
• researching Schwann cell and axonal interactions
• elucidating the role of the microenvironment, both during cell repair and cancer development
• and utilizing novel mouse models for the study of tumor development in Neurofibromatosis type 2 disease (NF2).

The Morrison lab has extensive experience in NF2 research including dissecting NF2 signaling pathways and is part of the international clinical consortium Synodos.

The adult brain responds and adapts to the multitude of stimuli that affect its functional and structural composition. This plasticity is reliant upon a continuous modification of neurons and their wiring, whereby neuronal networks are in a constant process of adaptation, resulting in the restructuring of synaptic connections. My lab research prioritizes Ras and Ras-like protein activity control in synaptic and structural neuroplasticity - the cellular basis for memory formation. This study of activity-dependent regulation of synapse efficacy is an important pathway for the healthy aging brain.

Current thinking positions mainly guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) as the major determinants in neuronal Ras regulation. Using primary in vitro culture systems and in vivo mouse models, we will explore the newly discovered components of small GTPase activity control and their subsequent effect on neuronal plasticity within the adult brain. Beyond the intracellular neuronal signaling pathways that regulate synaptic plasticity, we are also screening astrocyte dependent specific contact signals that promote neuron maturation.

In addition there is a widely held perception that the brain is a structure with limited regenerative capacity. However, it is now understood that new neurons and glia cells can be generated from stem cells within the adult central nervous system (CNS). This limited regenerative potency must be strictly controlled throughout life and is known to decline with age. Our goal is to dissect key signaling events and study the cellular components e.g. neural stem cell activity during regeneration. Our intention is to learn about the molecular pathways involved in neuroprotection and repair, to progress towards healthy brain aging as well as brain repair after injury.