Contact Details:

m.perretti@qmul.ac.uk

Mauro Perretti graduated in Pharmaceutical Chemistry (Faculty of Pharmacy) from the University of Florence, Italy, in 1985.  After an important spell at the Sclavo Research Centre in Siena, he joined the William Harvey Research Institute in 1991. Here he started to investigate the patho-physiology of the process of neutrophil trafficking as well as its pharmacological exploitation: he began a fruitful line of research centered on annexin 1 (then called lipocortin) and its effects on cell migration in vivo.  This work led the award of a Doctorate of Philosophy (Faculty of Science, University of London) in 1996.  In 1997 he won a Post-doctoral fellowship by the Arthritis Research Campaign UK, an award that was fundamental for his career. Senior Lecturer (1998-2000) at Bart’s and the London Queen Mary School of Medicine and Dentistry, he was rapidly promoted to Reader and given a personal chair (2001), prelude to the Senior Fellowship by the Arthritis Research Campaign UK (2002-2007).

Current research interests

Our laboratory (>12 scientists, students and visiting fellows) focuses on the investigation of the endogenous mediators that actively promote resolution of inflammation for the regain of tissue homeostasis. Natural (resolving) Inflammation results by a concerted regulation of several mediators, so that there exists an appropriate temporal and spatial balance between endogenous pro-inflammatory & anti-inflammatory mediators and pathways.

This multinational group studies specific elements of this endogenous response, with a dual approach: 1) on one hand, the patho-physiological relevance of these mediators in models of acute (air-pouch, peritonitis) and chronic inflammation (e.g. arthritis, endotoxaemia) is determined using a combination of molecular, cellular and integrate biology approaches (e.g. transgenic tools); 2) on the other hand, an equally important goal is identification of the target(s) mediating the effects of endogenous anti-inflammation as novel leads for innovative drug discovery: these new therapeutics will potentially produce much less side effects, since they will be mimicking the way our body naturally controls the inflammatory reaction.

Within the complexity of the inflammatory reaction, a strong area of interest is the regulation of leukocyte trafficking in the microcirculation; use of imaging techniques (e.g. intravital microscopy) is abundantly done (brain, mesentery, cremaster) as well as the use of genetically modified animals. Animal models are complemented by other analysis under flow (the flow chamber assay allows to study effects on leukocyte/endothelium interaction under flow using human cells). In the last 3-4 years, most if not all our lines of research, have been investigated for their translational potential, so that more and more work is devoted to determine if there are alterations (at the cellular or molecular levels) for any of the elements that form the pathways listed below. Diseases under investigation span from large vessel vasculitides to rheumatoid arthritis, from osteoarthritis to cystic fibrosis.

Under the research niche of endogenous anti-inflammation, the following mediators/systems are investigated:

• The Annexin A1 system, that is annexin 1 (the ligand), its receptor (a specific 7-TM GPCR termed FPRL-1 or ALX), its catabolism. Current studies involve assessment of the operative modes of this system on cells of innate as and adaptive immune response. In addition, drug development based on peptido-mimetics of the Annexin A1 N-terminal region is also a major interest.
  
  
• The melanocortin peptide system, focusing on the anti-inflammatory actions of ACTH and alpha-MSH, with a strong interest on i) the receptor responsible for these inhibitory effects (hence, potential selective agonist development programmes) and ii) the assessment whether agonists (such as ACTH and alpha-MSH) could be produced in the periphery by immune cells, leading to the discovery of an anti-inflammatory loop that might be generated locally, within the inflamed tissue, during the resolution phase of inflammation.
  
  
• Galectins, the anti-inflammatory effects of Galectin-1 have been studied predominantly in the context of endothelial cell biology. Use of transgenic approaches and silencing RNA (for human cells) is allowing definition of the role of this endothelial-derived protein on lymphocyte and neutrophil interaction, as assessed by intravital microscopy and the flow chamber assays. Novel lines are emerging, linking the pharmacological and pathophysiological functions of Galectin-1 and other members of this family of lectins, branching out of acute inflammation into more chronic experimental systems.
  
  
• New Projects, Opportunities are often explored to augment the efforts of this lab in elucidating novel and pivotal endogenous anti-inflammatory mediators and targets. Examples are current research on Resolvins (in collaboration with Prof CN Serhan, at Harvard) and Chemerin (in collaboration with Dr D Greaves, Oxford University).
  
  
• Glucocorticoids. A long-dated expertise in glucocorticoid biology (and anti-inflammatory effects) stemmed from the link between these hormones (and their synthetic derivatives) and annexin A1. Current interests are to reduce side effects of glucocorticoids therapeutic application: this is experimented in an innovative way, a major interest being analysis of the positive (reduction of arthritis) and negative (blockade of bone catabolism) interaction between Glucocorticoids and Calcitonin. Studies on non-genomic effects of glucocorticoids in platelets are also ongoing, with attention to RA.
  

 

Commercial Partnerships

Two patents associated to these projects have been licenced to Unigene Corp (Fairfield, NJ), a testimony to the constant attention for therapeutic development. As part of this deal, Perretti's lab will work together with this US Biotech to attain a therapeutic benefit from the potential synergism between calcitonin and glucocorticoids for the treatment of rheumatoid arthritis and other forms of arthritides. In addition, the Unigene Corp. proprietary know-how on peptide production and peptide oral delivery will be applied to the development of small fragments of the anti-inflammatory protein Annexin A1 for the treatment of post-ischaemic pathological conditions. Other collaborative projects are on-going with Action Pharma A/S (Copenhagen, DK) and UCB (Slough, UK).

 

Videos:

 

 

 

 

 

Key publications

 

• Gastardelo T, Damazo AS, Sawmynaden P, Dalli J, Flower RJ, Perretti M*, Oliani SM*. Functional and ultrastructural analysis of annexin A1 and its receptor in extravasating neutrophil during acute inflammation. AM J PATHOL 174:177-83, 2009.
  
  
• Hecht I, Jiang R, Sampaio AL, Hermesh C, Rutledge C, Shemesh R, Toporik A, Beiman M, Dassa L, Niv H, Cojocaru G, Zauberman A, Rotman G, Perretti M, Vinten-Johansen J, Cohen Y. A novel peptide agonist of FPRL1 (ALX) displays anti-inflammatory and cardioprotective effects. J PHARMACOL EXP THER 328:426-34, 2009.
  
  
• Perretti M, D’Acquisto. Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. NAT REV IMMUNOL 9: 62-70, 2009.
  
  
• Norling LV, Perretti M, Cooper D: Endogenous Galectins and the control of host inflammatory response. J ENDOCRINOL 201: 169-184, 2009.
  
  
• Piqueras L, Sanz MJ, Perretti M, Morcillo E, Norling L, Mitchell JA, Li Y, Bishop-Bailey D. Activation of PPAR{beta}/{delta} inhibits leukocyte recruitment, cell adhesion molecule expression, and chemokine release. J LEUKOC BIOL 86:115-122, 2009.
  
  
• McColl A, Bournazos S, Franz S, Perretti M, Morgan BP, Haslett C, Dransfield I. Glucocorticoids induce protein S-dependent phagocytosis of apoptotic neutrophils by human macrophages. J IMMUNOL 183: 2167-2175, 2009.
  
  
• Norling LV, Sampaio ALF, Cooper D & Perretti M: Inhibitory control of endothelial galectin-1 on in vitro and in vivo lymphocyte trafficking. FASEB J 22:682-90, 2008.
  
  
• Cooper D, Norling LV & Perretti M: Novel insights into the inhibitory effects of galectin-1 on neutrophil recruitment under flow. J LEUKOC BIOL 83:1459-1466, 2008.
  
  
• D'Acquisto F, Paschalidis N, Raza K, Buckley CD, Flower RJ & Perretti M. Glucocorticoid treatment inhibits annexin-1 expression in rheumatoid arthritis CD4+ T cells. RHEUMATOLOGY (Oxford). 47:636-9, 2008.

 

 

 

 

 

 

 

 

Search for more publications by Mauro Perretti

 

<< Return to staff list