Dr Tanya Smith
Approximately 70% of dialysis patients are male. However, women are more likely to be diagnosed with kidney disease. We do not understand why women appear to be protected from severe chronic kidney disease (CKD).
Ischemia Reperfusion Injury (IRI) is one of the most important contributors to CKD. It is a major contributor to Acute Kidney Injury (AKI) following which, failed kidney recovery may progress to CKD and the need for dialysis or a kidney transplant. There are no specific treatments for IRI and clinicians rely on the kidney’s intrinsic capacity to repair.
The mechanisms of kidney repair versus its failure following IRI are poorly understood. Proximal tubular cells (PTC’s) are the most abundant cell type in the kidney and are highly metabolically active, placing them at particular risk following ischemia. To date, PTC’s have typically been considered en masse, but in fact, heterogeneity in their responses has a key role in AKI resolution versus fibrosis. In response to our limited understanding of IRI in the kidney, researchers from our lab have identified new PTC phenotypes in renal fibrosis by a process known as single nuclear RNA sequencing (snRNAseq). We uncovered significant complexity in PTC phenotypes and identified PTC’s with discrete types delineated by unique expression profiles of disease-associated markers. The hypothesis of my PhD thesis is that there are sex-specific differences in PTC phenotypes that define responses to ischemic injury. The purpose of my project is to categorise these differences, uncover the key regulators of proximal tubular cell phenotype in this context, and test the effect of their manipulation.