Dr. Randall F. D'Souza
Background:
Non-alcoholic fatty liver diseases are the most prevalent chronic disease (NAFLD) worldwide. It usually presents as benign accumulation of hepatic lipids (NAFL), and can spontaneously escalate to more serious non-alcoholic steatohepatitis (NASH) which includes lipid accumulation, immune cell infiltration, inflammation and fibrosis. The mechanisms that underpin this escalation in pathology are poorly defined. Humans with liver disease express lower alpha-1-antitrypsin (A1AT) to neutrophil elastase (NE) ratios in circulating plasma and exogenous treatment with human A1AT in high fat diet fed mice reduced plasma NE content and liver markers of inflammation and neutrophil infiltration. A1AT is endogenously synthesized in the liver and functions to inhibit a range of neutrophil specific proteases including neutrophil elastase (NE) (the most abundant neutrophil specific proteolytic enzyme). We hypothesis therefore that neutrophil activation and infiltration into liver tissue is a critical step in the escalation of NAFL to NASH and that regulation of neutrophil proteases including NE via exogenous A1AT treatment may prevent and potentially treat diet-induced liver diseases in mice.
AIMS:
- Characterize hepatic neutrophil accumulation in NAFLD compared to NASH
- Can exogenous human-A1AT protect against diet-induced NASH?
- Is human-A1AT a likely therapeutic for the reversal of NASH?
Curriculum vitae Dr. Randall F. D'Souza
Dr. D'Souza obtained his PhD degree in Biomedical Science from the Liggins Institute, University of Auckland, New Zealand in November 2018. His PhD work was focussed on identifying novel muscle and circulatory microRNA biomarkers as predictors of changes in skeletal muscle mass, size and function to be applied in at risk populations.
Since 2018, he has been working as a postdoctoral fellow in the Discipline of Nutrition, Faculty of Medical and Health Sciences, University of Auckland, New Zealand. His current work focusses on understanding the mechanisms that underpin the development of non-alcoholic fatty liver diseases in mice and potential therapeutic strategies.