Miss Xinyi Ding1,2, Dr Jennifer Li1,2, Professor Natasha Rogers1,2, Professor Philip O'Connell1,2
1The Westmead Institute for Medical Research, Westmead, Australia, 2The University of Sydney, , Australia
Biography:
Bio to come
Aim:
To curate a novel, comprehensive cell death atlas of kidney injury and screening for druggable targets that can limit long-term damage to the kidney.
Background:
Long-term graft and patient survival after kidney transplantation have largely remained stagnant over the past 20 years, with only a handful of drugs being tested in the therapeutic pipeline. Most of the agents tested focus on modulating the excessive immune response in transplant rejection but little is available to limit cellular and tissue damage following immune activation. Limiting cell death, the severity of the injury, and subsequent maladaptive repair processes will significantly impact the preservation of the health and longevity of the transplanted kidney. Conventional mechanisms of cell death (apoptosis and necrosis) are important but many, pro-inflammatory forms of cell death (such as pyroptosis, necroptosis for example) have been discovered in the past 20 years. The relative importance of one cell death pathway over another, and how they coordinate and interact following kidney injury is unclear.
Methods:
Analysis of human kidney tissue of various kidney diseases at different time points using spatial technologies, including imaging mass cytometry and spatial transcriptomics.
Results:
Spatial transcriptomic (Visium) data and UMAP comparing the cell composition across non-rejected kidney and rejected kidney.
Conclusions:
There is a clear difference in the immune landscape between non-rejected kidney and rejected kidney where the rejected kidney shows a clear increase of specialised immune cell types within the influx of immune cells. The data also allows us to visualise the complex structure of the kidney more accurately with single-cell level of precision.