Human plasma extracellular vesicles during severe malaria – potential biomarkers of disease severity?
Extracellular vesicles (EVs), through their unique composition and ability to drive cell-cell communication have been identified as important players in the pathogenesis of several diseases. Associate Professor Valéry Combes and her team first found elevated EV numbers in the plasma of Malawian children with CM and demonstrated using animal models that EVs were likely involved in CM pathogenesis. They also showed the deleterious effects of EVs on endothelial integrity in an in vitro model of CM.
As both CM and severe malarial anaemia (SMA) result in high mortality rates and in survivors, significant neurocognitive impairment (NCI), the mechanisms of which remain unknown, in addition to their role in disease pathogenesis, we also hypothesised that the cargo of plasma malaria EVs aligned with the clinical status the patients and can be used a biomarker of disease severity.
Transcriptomic analysis of plasma EVs from Ugandan children with severe malaria with different clinical outcomes allowed us to identify microRNA with high prognostic value especially when distinguishing the outcomes of cerebral malaria. A comparative proteomic analysis was also conducted on similar samples and a series of differentially expressed proteins that could discriminate between children with cerebral malaria and severe malarial anaemia, as well as children who would develop neurocognitive impairment or succumb to complications was identified.
Associate Professor Valéry Combes will discuss these findings that suggest that early characterisation of EVs at the time of admission could inform the management of the patient. In addition, these omics analyses will allow the identification of molecules that are potentially associated with disease pathogenesis and will provide new treatment avenues where certain molecules carried by EVs could be targeted to prevent severe complications.
Speaker
Associate Professor Valéry Combes
Associate Professor Valéry Combes obtained her PhD in 2001 from the Universite de la Mediterranee (Marseille, France) on the role of endothelial microparticles in the pathogenesis of thrombotic diseases and moved to the University of Sydney in 2006. She is a vascular biologist with 25+ years of experience and leadership in the field of extracellular vesicle biology working on shifting the paradigm that extracellular vesicles (EVs) are not bystanders but true biological effectors notably in malaria infection.
In 2014, she joined the University of Technology Sydney where she is the Associate Head of School Education & Students in the School of Life Sciences and leads the Microvesicles and Malaria Research Group.
Valéry demonstrated the role of extracellular vesicles in cell-cell communication and also used experimental cerebral malaria in order to demonstrate the role of extracellular vesicles in the pathogenesis of this disease and to explore the role of their cargo. She is also studying the composition and role of EVs in human malaria, characterising the microRNA and protein content of patient plasma EVs and using in vitro models of the blood brain barrier to determine their role in the vascular lesions.
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