Our Group studies mechanisms of immune activation and tolerance in humans, discovering how the immune system works, with a focus on the interaction between metabolism and immune function. We aim at finding new ways to modulate the human immune response, important to restore homeostasis (which is defective in chronic inflammation) or boost the effector arm (beneficial when the body fights infection or cancer). To achieve this, we study how metabolites and metabolic routes interact with the immune response at the cellular and systemic levels. We envision that in the near future, we will be able to inform immune interventions through diet.
People
PhD Student
Senior Lecturer in Experimental Rheumatology
Projects
IL-10 regulation in effector T cells
IL-10 is a very potent anti-inflammatory cytokine and key to maintaining health. However, the molecular mechanisms that drive and control IL-10 expression are unclear, which hinders the possibility for targeting these pathways therapeutically. We focus on understanding how effector T cells can switch from a pro-inflammatory status towards homeostatic one by acquiring the ability to express IL-10. Because effector T cells are the main orchestrators of the immune response, we believe that the discovery of these molecular switches will allow for a more tailored manipulation of the overall immune response, important to maintain a healthy individual.
Cholesterol metabolism: a new tool for understanding and manipulating inflammation
Cholesterol is a key component of cellular structures, but its metabolic route also provides metabolites that are implicated in very important cellular processes such as signal transduction. It is also an infection rheostat, through the production of 25-hydroxycholesterol (25-HC). We have recently discovered novel functions of 25-HC in cells of the adaptive immune system, with potent immune-regulatory properties. We are now trying to understand the molecular mechanism behind the role of cholesterol homeostasis and 25-HC in controlling the outcome of the immune response. Interestingly, as systemic and cellular cholesterol are interlinked, our work will provide new knowledge on the influence of systemic cholesterol in the immune system.
Metabolic armouring for improvement of current immunotherapies
Metabolic restrictions and maladaptations dampen the ability of the immune system to maintain a healthy body. This is the case for metabolic diseases like obesity, but also in cancer, where metabolic competition between cancer and immune cells often drives immune cell exhaustion and tumour progression. We aim at understanding the metabolic constrains of immune cells in disease and design strategies that will help overcome these maladaptations and promote health. Recently, we have discovered that providing CAR T cells with the ability to metabolise fructose can bypass the metabolic competition for glucose and improve the anti-tumour response.
Publications
Awards
- Unravelling new immune-regulatory switches by manipulating cellular cholesterol metabolism in humans.
Springboard Acacemy of Medical Sciences - Immunometabolism in tolerance and inflammation: insights from checkpoint inhibitor therapy for solid tumours.
Medical Research Council – Doctoral Training Partnership - Neuroimmune and immunometabolic underpinnings of autism.
King’s College London - Multiscale Models for Life Centre for Doctoral Training - Investigating the role of TET2 in the regulation of cholesterol homeostasis in endothelial cells.
British Heart Foundation - Almonds and their impact on immune optimization to viral infection: a randomized controlled trial of vaccination model of immune response.
Almonds Board of California
Alumni
Perucha Lab Alumni:
- Carl Coyle - PhD student (2019-2022)
- Aoife O’Byrne - Research Assistant (2019-2020)
- Robert Page - PhD student (2018-2020)
- Jack Bibby - PhD student (2017-2019)
- Heather Cross - Research Assistant (2022-2023)
- Rozalyn Yorke - PhD student (2020-2024)
- Rebecca Milton - PhD student (2021-2024)
People
PhD Student
Senior Lecturer in Experimental Rheumatology
Projects
IL-10 regulation in effector T cells
IL-10 is a very potent anti-inflammatory cytokine and key to maintaining health. However, the molecular mechanisms that drive and control IL-10 expression are unclear, which hinders the possibility for targeting these pathways therapeutically. We focus on understanding how effector T cells can switch from a pro-inflammatory status towards homeostatic one by acquiring the ability to express IL-10. Because effector T cells are the main orchestrators of the immune response, we believe that the discovery of these molecular switches will allow for a more tailored manipulation of the overall immune response, important to maintain a healthy individual.
Cholesterol metabolism: a new tool for understanding and manipulating inflammation
Cholesterol is a key component of cellular structures, but its metabolic route also provides metabolites that are implicated in very important cellular processes such as signal transduction. It is also an infection rheostat, through the production of 25-hydroxycholesterol (25-HC). We have recently discovered novel functions of 25-HC in cells of the adaptive immune system, with potent immune-regulatory properties. We are now trying to understand the molecular mechanism behind the role of cholesterol homeostasis and 25-HC in controlling the outcome of the immune response. Interestingly, as systemic and cellular cholesterol are interlinked, our work will provide new knowledge on the influence of systemic cholesterol in the immune system.
Metabolic armouring for improvement of current immunotherapies
Metabolic restrictions and maladaptations dampen the ability of the immune system to maintain a healthy body. This is the case for metabolic diseases like obesity, but also in cancer, where metabolic competition between cancer and immune cells often drives immune cell exhaustion and tumour progression. We aim at understanding the metabolic constrains of immune cells in disease and design strategies that will help overcome these maladaptations and promote health. Recently, we have discovered that providing CAR T cells with the ability to metabolise fructose can bypass the metabolic competition for glucose and improve the anti-tumour response.
Publications
Awards
- Unravelling new immune-regulatory switches by manipulating cellular cholesterol metabolism in humans.
Springboard Acacemy of Medical Sciences - Immunometabolism in tolerance and inflammation: insights from checkpoint inhibitor therapy for solid tumours.
Medical Research Council – Doctoral Training Partnership - Neuroimmune and immunometabolic underpinnings of autism.
King’s College London - Multiscale Models for Life Centre for Doctoral Training - Investigating the role of TET2 in the regulation of cholesterol homeostasis in endothelial cells.
British Heart Foundation - Almonds and their impact on immune optimization to viral infection: a randomized controlled trial of vaccination model of immune response.
Almonds Board of California
Alumni
Perucha Lab Alumni:
- Carl Coyle - PhD student (2019-2022)
- Aoife O’Byrne - Research Assistant (2019-2020)
- Robert Page - PhD student (2018-2020)
- Jack Bibby - PhD student (2017-2019)
- Heather Cross - Research Assistant (2022-2023)
- Rozalyn Yorke - PhD student (2020-2024)
- Rebecca Milton - PhD student (2021-2024)
Our Partners
Group lead
Senior Lecturer in Experimental Rheumatology