Researching Host Response to Infections

Brendon Scicluna is Assistant Professor in the Center for Experimental Molecular Medicine and the Department of Clinical Epidemiology and Data science in the Amsterdam University Medical Center (Academic Medical Center, Amsterdam). Brendon’s research is focused on the systems biology of the host response to infections, with a particular emphasis on using genomics to better understand sepsis immunopathologies in the clinical context.

He obtained his Bachelor’s degree in chemistry from St. John’s University and the College of St. Benedict, Minnesota, and studied for a Master’s degree in molecular pathology at the University of Malta, Malta. After a short period in the pharma industry, Brendon was offered a PhD studentship in molecular cardiology at the Academic Medical Center, Amsterdam.

“My PhD focused on systems biology approaches to identify risk genes for cardiac electrical disorders, for example long QT and Brugada syndromes”.

Brendon works in COMBACTE-CARE’s WP1C – or MARS – a study that seeks to identify patients with pneumonia or abdominal sepsis who are at high risk for a poor outcome, based on molecular biomarkers expressed in blood leukocytes. Biomarker discovery studies performed in COMBACTE-CARE can contribute to optimizing patient selection in future studies.

“As a researcher in the successful MARS project, led by Marc Bonten and Tom van der Poll, I was approached to join the COMBACTE team in WP1C.

My primary role in WP1C is to identify host response biomarkers to delineate critically ill patients at high risk of mortality, after being diagnosed with sepsis due to hospital-acquired pneumonia or intra-abdominal infections.

WP1C was tasked with identifying candidate RNA biomarkers that could assist in identifying poor prognosis patients with sepsis due to abdominal or nosocomial (hospital-acquired) pneumonia. To this end, the team and I have measured RNA levels of over 60,000 transcripts in whole blood leukocyte samples obtained on ICU admission. We also had additional, and independent patient samples for validation purposes. The data and findings have been published in a recent issue of eLife (Scicluna BP etal eLife 2020 Dec 11;9:e58597).

The extensive data we have gathered will allow us to mine it deeper and deeper for years to come! Besides this, we have learned a lot and we’ll be applying that knowledge to similar types of analyses in the ASPIRE-ICU observational study. I am currently working on identifying alternatively spliced transcripts that could assist in diagnosis and prognosis of sepsis patients.”

In the last few years, Brendon has published papers on various aspects of the host response during sepsis, for example a clinical genomics study wherein he discovered four molecular endotypes in a cohort of sepsis patients from the MARS project. The endotypes, determined with samples obtained on ICU admission, may be used to predict poor prognosis (Scicluna BP et al Lancet Resp Med 2017;5(10):816-826).

“Together with colleagues in Nijmegen, we have uncovered novel biological pathways in sepsis that may represent exciting new avenues for treatment development, for example, a study that identified broad disturbances in immunometabolic processes in immune cells of sepsis patients (Cheng SC*, Scicluna BP*, Arts R* et al Nat Immunol. 2016;17(4):406-13.)” says Brendon. In addition, Brendon and his team found novel circular RNA molecules elevated in specific peripheral blood mononuclear cells of sepsis patients (Khan HN et al Crit Care 2020;24(1):423).