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Gabrielle Chappell
DPhil student
I am a third year DPhil student in the group of Associate Professor Jelena Bezbradica Mirkovic interested in the unique immunology of tissue resident macrophages. After my BSc in Mathematics and Biology at the University of St Andrews, I completed an MSc in Integrated Immunology at the University of Oxford. I began my DPhil at the Kennedy Institute of Rheumatology in October 2021, funded by a Kennedy Trust Prize Studentship.
My master’s thesis was supervised by Associate Professor Marco Fritzsche and investigated the relationship between calcium flux kinetics and immune synapse formation in T-cells. I have been a Summer Student for two years in the Surgery Branch of the National Cancer Institute (NCI) within the National Institutes of Health (NIH) in Bethesda, Maryland. During my time at the NIH, I worked in the labs of Dr. Nick Restifo and Dr. Steven Rosenberg, respectively, examining the role of lymphodepletion, radiation, vaccination, and exogenous IL-2 in immunotherapy models of adoptive T-cell transfer. My interest in macrophages was motivated from working in industry and studying how GM-CSF may drive cytokine release syndrome in the context of CAR-T cell therapy, graft-versus-host disease, and COVID-19 acute respiratory distress syndrome.
The NLRP3 inflammasome is a critical intracellular sensor of both sterile and pathogen-derived threats. As inflammasome activation results in highly inflammatory processes including cytokine release and pyroptosis, its activation must be tightly regulated. Tissue resident macrophages must be immunologically quiescent yet poised for phagocytic and anti-pathogen activity to maintain tissue homeostasis. Whether tissue resident macrophages possess unique pathways that suppress inflammasome activation is poorly characterised. I am currently studying inflammasome regulation in tissue resident macrophages within the synovium and how these mechanisms become dysregulated in the context of rheumatoid arthritis.
Recent publications
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Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial
Journal article
Temesgen Z. et al, (2022), The lancet respiratory medicine, 10, 237 - 246
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S49 C-reactive protein as a biomarker for improved efficacy of lenzilumab in Covid-19 patients: results from the LIVE-AIR trial
Conference paper
Temesgen Z. et al, (2021), Developing treatments for covid-19
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C-REACTIVE PROTEIN AS A BIOMARKER FOR IMPROVED EFFICACY OF LENZILUMAB IN PATIENTS WITH COVID-19: RESULTS FROM THE LIVE-AIR TRIAL
Journal article
TEMESGEN Z. et al, (2021), Chest, 160, A2522 - A2524
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GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia
Journal article
Temesgen Z. et al, (2020), Mayo clinic proceedings, 95, 2382 - 2394
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An effective mouse model for adoptive cancer immunotherapy targeting neoantigens
Journal article
Hanada K-I. et al, (2019), Jci insight, 4