School of Medical Sciences

Current research projects

Targeting a common pathway in neurodegeneration

Our studies on the CNS show that gap junctions regulate the neuroinflammatory response and disrupt the positive feedback driven by activation of the inflammatory mediators - astrocytes and microglia. This chronic neuroinflammation follows regardless of the initial disease trigger. Connexin43 is upregulated in CNS injury and plays a significant role in the spread of damage, the neuroinflammatory response and accompanying oedema.

We are investigating the cell-specific expression of gap junction proteins in PD human brains, since we believe that regulation of gap junction protein expression and function may offer a potential treatment for the chronic inflammation characteristic of neurodegenerative diseases of the brain.


Identifying potential targets to halt the progression of Parkinson's disease

Oxidative stress, inflammation, glial cell activation and formation of neuronal cell inclusion bodies (Lewy body) are implicated in the progressive cell loss in PD but the mechanisms remain unknown. Oxidative stress accelerates the interaction between carbohydrates and proteins, called glycation, resulting in the accumulation of glycation products known as Advanced Glycation End products (AGEs). AGEs can activate glial cells and exert harmful effects via the receptor for Advanced Glycation End products, RAGE. RAGE is expressed on a number of cell types, including glial cells and neurons. The AGE-RAGE interaction can lead to a number of cytotoxic effects including inflammation. Inflammatory signals spread via cell-to-cell connections called gap junctions.

We are investigating the complex interaction between neurons and glial cells involving 'cross talk' amongst AGE, RAGE, and connexin as critical pathway in progressive cell death in Parkinson's disease.


Regulation of cell to cell communication for spinal cord injury – taking the next step

Spinal cord injury results in a devastating loss of mobility for the victim. After the initial injury, damage spreads, leading to a significant increase in the size of the area affected. This damage spread is caused by transfer of neurotoxins from the damage site to otherwise healthy tissue via intercellular channels called gap junctions.

We aim to 'block' these channels at the time of injury, using small protein molecules, in order to significantly reduce the damage spread. We believe this powerful new approach will lead to significantly improved outcomes for spinal injury victims.


Connexins as key players in neuronal differentiation

A major feature of many neurological disorders is the death of populations of neurons. Replacing lost cells with new neurons - cell transplantation therapy - offers great promise. We need to better understand the 'factors' that control neuronal differentiation - how precursor cells transform into neurons.

The cells of the developing brain exhibit a whole array of different connexins as they mature and changes in connexins are increasingly being seen as fundamental to cellular processes.

We are investigating ways of controlling gap junction proteins expressed during development to see if we can drive neuronal differentiation, with the goal of using this technology as an approach to assist brain repair.


The role of connexins in adult neurogenesis

The adult central nervous system contains stem cells that differentiate into neurons throughout adult life. These cells migrate to areas of the brain and spinal cord where cells are lost under normal conditions or as a result of disease or injury. Connexins are involved in the generation and migration of new neurons in the developing brain. We are investigating whether connexins also play a similar role during neurogenesis in the normal or injured adult brain and spinal cord.