My research focuses on better understanding the early events in the brain that contribute to neurological disorders such as Alzheimer’s Disease. We use human neurons grown in plastic dishes for our experiments. The cells originally come from human skin samples and these skin cells are ‘reprogrammed’ to become stem cells that have the potential to generate any cell in the human body. These are known as ‘induced pluripotent stem cells’ or iPSCs.
Using a cocktail of biological factors, we direct the iPSCs to become neurons and this provides a model of human neuronal development: the iPSCs are instructed to make a pool of neuronal progenitor cells that over time, give rise to neurons that can no longer divide. These neurons mature, make connections or synapses with one another to generate a neuronal network, and are electrically active, similar to cells found in the body. We can generate human neurons from both healthy controls and from those people who carry rare genetic mutations that give rise to inherited forms of Alzheimer’s Disease.
We are investigating the idea that that there are subtle changes in synapses that precede the onset of neurological symptoms. If we can understand these harmful early synaptic changes, we may be able to design strategies to correct them and ultimately prevent synapse and neuronal loss, the events considered to underlie memory loss seen in patients. We also use this human model to ask fundamental questions about normal brain development. For example, how is neurogenesis regulated in human neuronal progenitor cells and how do they contribute to the different types of mature neuron found in the human brain? These questions will keep us busy for years to come and will ultimately impact our understanding of how the brain develops, matures and ages.
As well as research, I teach on the MSc in Pharmacology and on the Pluripotent Stem Cell Technology Workshop, run by the Department of Continuing Education
A Highly Efficient Human Pluripotent Stem Cell Microglia Model Displays a Neuronal-Co-culture-Specific Expression Profile and Inflammatory Response.
Haenseler W. et al, (2017), Stem cell reports, 8, 1727 - 1742
Neuronal Chloride Regulation via KCC2 Is Modulated through a GABAB Receptor Protein Complex.
Wright R. et al, (2017), J neurosci, 37, 5447 - 5462
Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics.
Handel AE. et al, (2016), Hum mol genet, 25, 989 - 1000
The hematopoietic chemokine CXCL12 promotes integration of human endothelial colony forming cell-derived cells into immature vessel networks.
Newey SE. et al, (2014), Stem cells dev, 23, 2730 - 2743
Microvessel networks pre-formed in artificial clinical grade dermal substitutes in vitro using cells from haematopoietic tissues (vol 38, pg 691, 2012)
Athanassopoulos A. et al, (2013), Burns, 39, 194 - 194