Dr. Mauro Corrado
Research Area: Immunometabolism, Mitochondrial Biology, Inflammation
1. Research Background:
The research in my group focuses on the role of mitochondrial metabolism, and in particular of cardiolipin (the distinctive inner mitochondrial membrane phospholipid), in shaping immunity, inflammation, and ageing. The importance of cardiolipin in mitochondrial function is evidenced not just by the X-linked inherited pathology Barth syndrome, a result of cardiolipin remodeling deficiency but also by its role in many conditions ranging from neurodegeneration to traumatic brain injury, from multiple sclerosis to heart failure.
We have showed how the dynamic synthesis and remodeling of cardiolipin is responsible for the metabolic and functional plasticity of CD8+ T cells during an immune response (Corrado et al., 2020). Our research also highlights CD8+ lymphopenia and functional impairments as previously uncharacterized features of Barth syndrome, where patients have Tafazzin mutations and so defective cardiolipin remodeling. Moreover, our recent work on the metabolic regulation of thymic development has shown how metabolism influences the immune system starting from the developmental stage (Corrado et al., 2021). This is important because one of the first manifestations of ageing is thymic involution.
Our lab is also interested in how mitochondria participate and amplify inflammatory signals. Indeed, in addition to their metabolic roles, mitochondria can release damage-associated molecular patterns (DAMPs) to activate inflammation or prevent it during apoptosis. Interestingly, during ageing progressive decline in mitochondrial function is linked to higher systemic inflammation in a process called “inflammageing”.
2. Research questions addresses by the group:
- How does mitochondrial fitness regulate T cell differentiation and function? How can we harness metabolism to modulate T cell function (improving it in the context of cancer immunotherapy or blocking it in case of autoimmunity)?
- What are the systemic consequences of immune cell metabolic decline during ageing? Can we counteract this process and improve healthspan and immune function during ageing?
- How do mitochondrial deficiencies modulate inflammation? Which inflammatory pathways are activated when mitochondria are dysfunctional?
To answer these questions, we use metabolomics and high throughput screenings in combination with deep in vivo immunephenotyping in mice. We aim to translate our findings in the context of cancer immunotherapy, metabolic diseases and mitochondrial-related pathologies.
3. Possible project(s):
We offer multi-disciplinary projects that combine classic immunology experiments to study in vivo T cell immunity in transgenic mouse models in the context of infection, cancer and autoimmunity and integrate them with state-of-the-art metabolomic and high throughput approaches to characterize their metabolism and function.
4. Applied Methods and model organisms:
We use genetic mouse models to study the mechanisms regulating immunity, tissue homeostasis and inflammation in vivo. We combine in vivo mouse phenotyping with in vitro biochemical, genome editing techniques and quantitative proteomics and metabolomics by mass spectroscopy. We are developing high throughput screenings to mechanistically define the metabolic rewiring and inflammatory pathways activated in metabolically impaired immune cells..
5. Desirable skills and qualifications:
We are seeking a highly motivated PhD candidate to join our team investigating the role of metabolism in shaping the immune response. Applicants should have a solid background in cell biology, biochemistry and immunology. Experience in mouse experimentation would be advantageous but is not a prerequisite.
- Corrado M, Edwards-Hicks J, Villa M et al., Dynamic cardiolipin synthesis is required for CD8+ T cell immunity. Cell Metabolism (2020); 32 (6): 981-995. e7.
- *Corrado M, Samardzic D, Giacomello M et al., Deletion of the mitochondria-shaping protein Opa1 during early thymocyte maturation impacts mature memory T cell metabolism. Cell Death and Differentiation (2021); 28: 2194-2206. *Corresponding author
- *Corrado M, Pearce EL: Targeting memory T cell metabolism to improve immunity, The Journal of Clinical Investigation (2022); 132: 1. *Corresponding author
- *Simula L, *Corrado M, Accordi B et al., JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction. Cell Death and Differentiation (2020); 27: 2749-2767. *Equal contribution
- Klein Geltink RI, O’Sullivan D, Corrado M, et al., Mitochondrial priming by CD28. Cell (2017); 171 (2): 385-397 .e11