Mauro, Claudio

Reader in Metabolism and Inflammation / British Heart Foundation Research Fellow

I graduated from the University of Naples “Federico II” (Italy) with a degree in Medical Biotechnology in 2002 and a PhD in Molecular Oncology and Endocrinology in 2007.

During my PhD (2002-07) I studied the pro-inflammatory and anti-apoptotic response controlled by the NF-kappaB family of transcription factors. This work led to the publication of 8 papers, including 5 as the first author (Biochem Biophys Res Comm 2003, J Biol Chem 2004, 2x J Biol Chem 2006, J Neurol Neurosurg Psychiatry 2008). In these studies I discovered novel mechanisms of activation of NF-kB downstream of TNF receptors and upon endoplasmic reticulum stress and the contribution of NF-kB activity to thyroid tumourigenesis.

During my postdoc (2007-11) – supported in part by an Immediate Fellowship from the Italian Association for Cancer Research – I worked both at the University of Chicago (USA) and Imperial College (UK) at the identification of the molecular links between inflammation and metabolism in the adaptive immune system and in cancer. This work led to the publication of 3 papers as the first author (Methods Mol Biol 2009, Proc Natl Acad Sci 2010, Nat Cell Biol 2011).

Since I moved to the William Harvey Research Institute in 2011, I worked towards establishing an innovative line of research, identified as “Immunometabolism control in inflammation”, aimed at investigating the metabolic control of T cell effector functions and the implications of the metabolic dependence of immune responses in physiology and inflammation. This work led to the award of an Intermediate Basic Science Research Fellowship from the British Heart Foundation in 2012 and the publication of a number of papers in the field, including Mol Cell Proteomics 2014, PLoS Biol 2015, Trends Biochem Sci 2016, Eur J Immunol 2016 and Cell Metab 2017

Summary of Research

My focus is on inflammatory conditions of the cardiovascular system and the joints, including atherosclerosis, obesity and rheumatoid arthritis. Low-grade T cell-mediated inflammation is associated with these conditions and contributes to their pathogenesis and progression. Our studies indicate that interfering with metabolic pathways (i.e., lipid, glucose and oxidative metabolism) altersT cell effector functions in vitro and in vivo. The hypothesis we are investigating is that systemic metabolic alterations in cardiovascular disease and rheumatoid arthritis (RA) lead to aberrant T cell responses and migration patterns, which favour the establishment of chronic inflammation (PLoS Biol 2015, Cell Metab 2017). We are exploring the mechanisms of metabolic control of T cell-mediated immune responses, including migration, differentiation and cytokine production in physiology and under metabolic stress. We are also investigating the effect of drugs that correct altered metabolism (e.g., the antidiabetic drug metformin) on T cell trafficking and inflammation in murine models of atherosclerosis, obesity and RA. These studies are proving crucial to provide insights into the role of energy balance on physiologic T cell-mediated immune responses and the effect of altering metabolism on the development of T cell-mediated inflammation, as well as new therapeutic targets to prevent inflammation in these human conditions.

 

Members of the Group

Current members:

Dr Joanne Smith (British Heart Foundation-funded graduate research assistant)
Dr Danilo Cucchi (British Heart Foundation-funded postdoctoral research assistant)
Dr Valentina Pucino (ARUK Clinical Research Fellow; co-supervision with Professor Pitzalis and Dr Bombardieri)
Mr Christopher Sefia (SBCS undergraduate student)
Mr David Tang (4th year medical student)

Former members:

Dr Robert Haas, PhD (2016) – Postdoc at the Crick Institute
Dr Ken Cheung, PhD (2015) – Postdoc at QMUL
Ms Ridhika Poojara, MRes (2015) - Research assistant at Imperial College
Ms Claire Macdougall MRes (2015) - PhD student at QMUL
Ms Jayna Narendra, MRes (2014) - PhD student at QMUL
Mr Shoaib Ansar Nasim, BSc (2016) - Medical student at Imperial College
Mr Chris Palmer-Jones, BSc (2014) - Medical student at QMUL

Key Publications

For a full list of publist publications click here

Mauro C (corresponding), Smith J, Cucchi D, Coe D, Fu H, Bonacina F, Bagaretti A, Cermenati G, Caruso D, Mitro N, Catapano AL, Ammirati E, Longhi MP, Okkenhaug K, Norata GD  and Marelli-Berg FM (2017). Obesity-induced metabolic stress leads to biased effector memory CD4+ T cell differentiation via PI3K p110delta-Akt-mediated signals. Cell Metab, 25:593-609 10.1016/j.cmet.2017.01.008
Commentary in: Chapman NM and Hongbo C (2017). Dietary fat inflames CD4+ T cell memory in obesity. Cell Metab, 25:490-2 10.1016/j.cmet.2017.02.012

Pucino V, Bombardieri M, Pitzalis C and Mauro C (2016). Lactate at the crossroads of metabolism, inflammation and autoimmunity. Eur J Immunol, 47:14-21 10.1002/eji.201646477

Haas R, Cucchi D, Smith J, Pucino V, Macdougall CE and Mauro C (2016). Intermediates of metabolism: from bystanders to signaling molecules. Trends Biochem Sci, 41:460-71 10.1016/j.tibs.2016.02.003

Haas R, Smith J, Rocher-Ros V, Nadkarni S, Montero-Melendez T, D’Acquisto F, Bland EJ, Bombardieri M, Pitzalis C, Perretti M, Marelli-Berg FM and Mauro C (2015). Lactate regulates metabolic and pro-inflammatory circuits in control of T-cell migration and effector functions. PLoS Biol,13:e1002202 10.1371/journal.pbio.1002202 

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