reSEArch-EU - European University of the Seas

Title: “Epigenetic properties of immune cell functions: implications for sepsis pathophysiology”

Abstract

Sepsis is a complex syndrome understood to be initiated by a dysfunctional host response to infection leading to lethal organ dysfunction. The global incidence was estimated at 48.9 million cases in 2017, with 11 million sepsis-associated deaths worldwide. Respiratory infections, particularly pneumonia, are a major determinant of sepsis, and leading cause of mortality especially in elderly populations. It is expected that sepsis will remain a global problem due to a combination of factors, including a progressively ageing population, surgical interventions, antimicrobial resistance and emergence of viruses with pandemic potential. Several clinical trials targeting components of the inflammatory response during sepsis have so far resulted in no significant improvements. Those numerous shortcomings have been ascribed to patient heterogeneity and incomplete knowledge of sepsis pathophysiology.

By leveraging on the genomics and machine learning toolkit, my work has uncovered novel immunopathological pathways, identified candidate diagnostic biomarkers, and stratified patients as molecular subgroups (or endotypes) with pathophysiological and clinical implications. Altogether, classifying sepsis patients as blood molecular endotypes revealed that poor prognosis sepsis was characterized by a state of immunosuppression, and manifestation of septic shock. The latter representing a major complication of sepsis reflecting vascular endothelium failure. My recent work in functional genomics has shown that circulating monocytes obtained from patients hospitalized due to community-acquired pneumonia (CAP), a major determinant of sepsis, manifested impaired cytokine production indicative of immunosuppression, which was explained considerably by an epigenetic and transcriptomic axis. Notably, even after one-month recovery cytokine production capacities of circulating monocytes from the same CAP patients were not fully resolved.

Brendon P. Scicluna short CV

Before joining the University of Malta in 2022 as Assistant Professor in Applied Biomedical Science, Dr. Scicluna held a tenured position at the respected Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands, as well as faculty position in the Center for Experimental Molecular Medicine, Amsterdam Institute of Infection and Immunity. Dr. Scicluna’s research focuses on immunobiology and pathophysiology of sepsis, critical illness due to non-infectious aetiologies, immunity, and cancer. Dr. Scicluna’s work is published in several prestigious international journals that include Nature, Nature Immunology, Nature Reviews Immunology, Journal of the American Medical Association, Lancet Respiratory Medicine, Cell Metabolism, Genome Medicine and the American Journal of Respiratory and Critical Care Medicine.

He has authored more than 130 peer-reviewed publications with a web of science H-index of 30. His recent work in identifying sepsis molecular endotypes with clinical implications, published in Lancet Respiratory Medicine, has been highlighted as a key bridge to fulfil the promise of personalized medicine in the context of infectious diseases and intensive care medicine. He is an active member of international consortia, including a Personalized Immunotherapy for Sepsis consortium (IMMUNOSEP), a transatlantic Sepsis Subclasses consortium, and the Combatting Antimicrobial Resistance in Europe (COMBACTE) consortium. Dr. Scicluna is a member of the European Society of Intensive Care Medicine, European Group for the Immunology of Sepsis, American Thoracic Society and the European Shock Society. He is recipient of various awards, including the recent prestigious European Society of Intensive Care Medicine Established Investigator award.

Dr. Scicluna read for his undergraduate degree at St. John’s University and the College of St. Benedict, Collegeville, Minnesota, USA, which he followed with a Master of Science degree from the University of Malta. He then joined the University of Amsterdam’s Academic Medical Center to read for his Ph.D. specializing in Experimental Medicine. Dr. Scicluna has collaborated with several respected research groups in the USA, Europe and United Kingdom. He has mentored several graduates, post-graduate students, and doctoral students (five) having successfully defended their thesis including a cum laude. He is a much sought-after mentor by post-doctoral fellows from all over the globe, including Sweden, United Kingdom and Japan. He currently teaches undergraduate and graduate courses in molecular biology, genomics, genetics, research methods, model organisms in biological research, applied molecular bioscience and data science at the University of Malta.

brendon.scicluna@um.edu.mt