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I have always been fascinated by how cells integrate hundreds of different environmental cues into specific responses in a fast and accurate fashion. Cells achieve this functional plasticity by sensing extracellular factors present in their milieu, which engage cell surface receptors and trigger a cascade of downstream signalling events that ultimately result in alterations of cell function and fate. Cytokines are such factors and control every aspect of the immune response, making them the perfect model system to study how information is transmitted from the plasma membrane into cellular responses. My first contact with cytokines occurred during my PhD studies in Dr. Sandra Pellegrini’s laboratory at the Pasteur Institute in Paris, France. My work on the type I Interferon system showed that cells dynamically manipulate their responses to any given ligand by altering their proteome. In particular I showed that cell surface receptor density, which is actively controlled by cells, is a key determinant of differential activities exhibited by cytokines.
This work got me interested in the role that cytokine receptors play in determining the specificity of signalling outputs. Though trained in biochemistry and molecular cell biology, I appreciated the key importance of structural biology to tackle this problem and decided to join Prof. Chris Garcia's laboratory at Stanford University, USA, who was at the forefront of cytokine structural analyses. During my postdoctoral studies, I applied protein engineering and structural biology to truly re-engineer the geometry of a cytokine receptor complex and could unambiguously show differential signalling induced by different ligand-receptor binding geometries. This work has opened completely new avenues to design synthetic cytokines with tailored therapeutic properties.
In my laboratory in the Cell Signalling and Immunology Department at University of Dundee, I continue pursuing my interest in cytokine signalling and cytokine functional pleiotropy at the mechanistic level. By quantitatively mapping downstream signalling events using biochemical, genetic, engineering and fluorescence imaging techniques I plan to pinpoint the events critical for cellular decisions and to exploit this insight to generate synthetic cytokine agonists with tailored functional properties for potential pharmaceutical application.
Research Interests
Papers共 60 篇Author StatisticsCo-AuthorSimilar Experts
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Nature Communicationsno. 1 (2024): 1-11
The FEBS journalno. 10 (2023): 2525-2552
bioRxiv (Cold Spring Harbor Laboratory) (2023)
Elsevier eBookspp.37-64, (2022)
Proceedings of the National Academy of Sciences of the United States of Americano. 33 (2022): e2112006119-e2112006119
crossref(2022)
Reference Module in Biomedical Sciences (2021)
Cell reportsno. 12 (2020): 108545-108545
C. Gorby, J. Sotolongo Bellón,S. Wilmes,W. Warda,E. Pohler,P.K. Fyfe,A. Cozzani,C. Ferrand,M.R. Walter,S. Mitra,J. Piehler,I. Moraga
Science Signalingpp.1-46, (2020)
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Author Statistics
#Papers: 60
#Citation: 2332
H-Index: 22
G-Index: 35
Sociability: 6
Diversity: 2
Activity: 4
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