Contact Details:

f.dacquisto@qmul.ac.uk

Fulvio D’Acquisto graduated in Pharmaceutical Chemistry in 1993 from the University of Naples “Federico II” and trained in Pharmacology at the Department of Experimental Pharmacology of the Faculty of Pharmacy. In 1996 he obtained the Master in Experimental Pharmacology working on mechanisms by which Annexin-A1 exerts an exquisite control on gene expression in inflammation.

During his PhD in Experimental Pharmacology (1996 to 1999) he studied the role of the transcription factor NF-B in different models of acute and chronic inflammation demonstrating that inhibitors of NF-kB activation display a remarkable in vivo anti-inflammatory activity. He directed his efforts on this research path even further after beginning his post-doctoral training in the laboratory of Prof. Sankar Ghosh, at Yale University (1999), where he investigated novel approaches to successfully target the NF-κB pathway and that can be used as anti-inflammatory therapy (Science, 2000, 289:1550-1554; Nat Med, 2004, 10:617-624). During this time (from 1999-2003) he expanded his knowledge on inflammation by focusing on immune-mediated inflammatory diseases and investigated signalling pathways by which the T cell receptor activates NF-κB in T cells (Immunity, 2003, 18:763-775; Science, 2005, 308:114-118).

Since July 2003, he joined Prof. Perretti and Prof Flower’s lab at WHRI where he re-activated his long-term interest in Annexin-A1 biology, starting a unexplored path in the role of this protein in the adaptive immune response. In December 2004 he was awarded the New Investigator Award of the Medical Research Council. In 2006 he was appointed as Senior Lecturer in Immunopharmacology within the Centre for Biochemical Pharmacology at WHRI. He has just been conferred the title of Reader in Immunopharmacology (October 2009).

 

Current research interests

 

Research theme 1: Role of Annexin-A1 in the adaptive immune response

Dr. D’Acquisto main research interest focuses on the multiple functions and properties of Annexin-A1 in the adaptive immune system. During his MRC New Investigator Award he focused his attention on the biological role of Annexin-A1 in T cell activation and differentiation. From this work, six main research areas have developed:

Analysis of Annexin-A1 functions in mature T cells. Annexin-A1 acts as positive modulator of T cell activation (D’Acquisto et al., Blood. 2007;109:1095-102; D’Acquisto et al. Eur J Immunol. 2007;37:3131-42). In light of these findings, he is now investigating the role of endogenous Annexin-A1 and its receptor Formyl Peptide Receptor (FPR) in T cell activation and differentiation focusing - in particular - on Th1/Th2/Th17 lineages and their possible correlation with the development of autoimmune diseases. In collaboration with Prof. Mauro Perretti (WHRI), he won an ARC PhD studentship to generate transgenic mice overexpressing Annexin-A1 specifically in T cells, as a novel tool for investigating the impact of this protein on T cell activation and differentiation.

Role of Annexin-A1 in thymocyte positive and negative selection. In collaboration with Prof. Tessa Crompton (Institute of Child Health, University College London), he has investigated the role of endogenous Annexin-1 in positive and negative selection in the thymus using Annexin-A1 deficient mice (Paschalidis et al., Cell Cycle, 2010, 9:784-93). He is now investigating how increased expression of Annexin-A1 influences positive and negative selection using the T cell specific Annexin-A1 transgenic mice in conjunction with HY, OT-I and OT-II TCR transgenic mice as well as the role of this protein in glucocorticoid-induced tolerance.

Investigating the cross-talk between T cells and Antigen Presenting Cells influences the adaptive immune response. Another important cell in adaptive immune response is the dendritic cell. Supported by a PhD studentship of the Barts and the London Charitable foundation, he has discovered the role of endogenous Annexin-A1 in dendritic cell activation and differentiation (Huggins et al., FASEB J. 2009;23:985-96). He is now expanding these observations investigating how Annexin-A1 influences TLR signalling pathways in macrophages and dendritic cells and how these changes would affect, in turn, T cell activation and skewing in effector T helper cells.

Role of Annexin-A1 in autoimmune diseases. This is a major research interest. He has generated a novel and unique colony of mice over-expressing Annexin A1 selectively in T cells. The plan is to exploit this new colony to investigate the correlation between glucocorticoids and Annexin-A1 in rheumatoid arthritis (D’Acquisto et al., Rheumatology 2008; 47:636-9). Another potential application is for Multiple Sclerosis. He won an Innovative Award of the Multiple Sclerosis society aimed at investigating the role of Annexin-A1 in a mouse model of multiple sclerosis using both Annexin-A1 deficient (Paschalidis et al., J. of Neuroinflammation. 2009; In press) and Annnexin-1 transgenic mice. In collaboration with Dr. Pasquale Maffia and Dr. James Brewer (Division of Immunology, Infection & Inflammation, Glasgow Biomedical Research Centre, University of Glasgow) he is exploring the role of Annexin-A1 in the development of atherosclerosis as well as in the breach of self-tolerance.

Generation of humanized Annexin-1 neutralizing antibodies. Supported by Heptagon Fund, this project aims at developing novel neutralizing antibodies against Annnexin- A1 for the treatment autoimmune disease. Following the successful funding award, QMI was able to negotiate two commercial licences agreement with Medannex, a biotechnology company, who is currently supporting the project.

Impact of Annexin-A1 cleavage on its biological activity. In collaboration with Prof. Perretti (WHRI; see also Vong et al. J Biol Chem. 2007 12;282:29998-30004), he has engineered novel species of this anti-inflammatory protein which are resistant to cleavage and are endowed with prolonged and potent anti-inflammatory properties (Pederzoli-Ribeil et al., Blood, 2010, 116:4288-96). This study is funded by the British Heart Foundation.

Research theme 2: Inflammatory properties of T cell derived cytokines

The main aim of this research is to characterize the inflammatory effects of novel cytokines produced by Th effector cells. He has recently investigated the inflammatory properties of Interleukin-17 in classical mouse models of inflammation (Maione et al. Biochem Pharmacol. 2009; 77:878-87) as well as its effect on human platelets (Maione et al., Biochem Biophys Res Commun, 2011). He is now expanding these studies and characterizing the effects of “novel” inflammatory cytokines” (D’Acquisto et al., Biochem Pharmacol. 2009) in classical models of inflammation.

Research theme 3: Role of “unconventional” T cells in inflammation

In collaboration with Prof. Tessa Crompton (Institute of Child Health, University College London), he is characterizing the inflammatory response in mice bearing a deficient adaptive immune system focusing on particular on the role of “unconventional” T cells (Maione et al., Autoimmunity, 2010, 43:672-81; D'Acquisto and Crompton Biochem Pharmacol, 2011).

Research theme 4: Pain and the adaptive immune response

In collaboration with Dr. Marzia Malcangio (Wolfson CARD, King's College London), he is investigating how the adaptive immune system might influence pain sensation during inflammation (Leger et al., J Neuroimmunol. 2011; Staniland et al., J Neurochem, 2011, 114:1143-57).

 

Key publications for each research theme

 

Role of Annexin-A1 in the adaptive immune response

• L Spurr, S Nadkarni, M Pederzoli-Ribeil, NJ Goulding, M Perretti, F D'Acquisto: Comparative analysis of Annexin A1-formyl peptide receptor 2/ALX expression in human leukocyte subsets. Int Immunopharmacol, 2011, 11:55-66.

• M Pederzoli-Ribeil, F Maione, D Cooper, A Al-Kashi, J Dalli, M Perretti, F D'Acquisto: Design and characterization of a cleavage-resistant Annexin A1 mutant to control inflammation in the microvasculature. Blood, 2010, 116:4288-96.

• N Paschalidis, A Huggins, NJ Rowbotham, AL Furmanski, T Crompton, RJ Flower, M Perretti, F D'Acquisto: Role of endogenous annexin-A1 in the regulation of thymocyte positive and negative selection. Cell Cycle, 2010, 9:784-93.

• D Renshaw, T Montero-Melendez, J Dalli, A Kamal, V Brancaleone, F D'Acquisto, G Cirino, M Perretti: Downstream gene activation of the receptor ALX by the agonist annexin A1. PLoS One, 2010, 5.

• N Dufton, R Hannon, V Brancaleone, J Dalli, HB Patel, M Gray, F D'Acquisto, JC Buckingham, M Perretti, RJ Flower: Anti-inflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. J Immunol, 2010, 184:2611-9.

• M Perretti, F D'Acquisto: Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol 2009, 9:62-70.

• N Paschalidis, AJ Iqbal, F Maione, EG Wood, M Perretti, RJ Flower, F D'Acquisto: Modulation of experimental autoimmune encephalomyelitis by endogenous annexin A1. J Neuroinflammation 2009, 6:33.

• A Huggins, N Paschalidis, RJ Flower, M Perretti, F D'Acquisto: Annexin-1-deficient dendritic cells acquire a mature phenotype during differentiation. FASEB J 2009, 23:985-96.

• F D'Acquisto: On the adaptive nature of annexin-A1. Curr Opin Pharmacol 2009, 9:521-8.

• F D'Acquisto, M Perretti, RJ Flower: Annexin-A1: a pivotal regulator of the innate and adaptive immune systems. Br J Pharmacol 2008, 155:152-69.

• F D'Acquisto, N Paschalidis, K Raza, CD Buckley, RJ Flower, M Perretti: Glucocorticoid treatment inhibits annexin-1 expression in rheumatoid arthritis CD4+ T cells. Rheumatology (Oxford) 2008, 47:636-9.

Inflammatory properties of T cell-derived cytokines

• F Maione, C Cicala, A Liverani, N Mascolo, M Perretti, F D'Acquisto: IL-17A increases ADP-induced platelet aggregation. Biochem Biophys Res Commun, 2011 Apr 22.

• F Maione, N Paschalidis, N Mascolo, N Dufton, M Perretti, F D'Acquisto: Interleukin 17 sustains rather than induces inflammation. Biochem Pharmacol 2009, 77:878-87.

• F D'Acquisto, F Maione, M Pederzoli-Ribeil: From IL-15 to IL-33: the never-ending list of new players in inflammation. Is it time to forget the humble aspirin and move ahead? Biochem Pharmacol, 2010, 79:525-34.

Role  of “unconventional” T cells in inflammation

• F Maione, N Paschalidis, AJ Iqbal, T Crompton, M Perretti, F D'Acquisto: Analysis of the inflammatory response in HY-TCR transgenic mice highlights the pathogenic potential of CD4- CD8- T cells. Autoimmunity, 2010, 43:672-81.
  
  
• F D'Acquisto and T Crompton: CD3+CD4-CD8- (double negative) T cells: saviours or villains of the immune response? Biochem Pharmacol, 2011.

Pain and adaptive immune response

• T Leger, J Grist, F D'Acquisto, AK Clark, M Malcangio: Glatiramer acetate attenuates neuropathic allodynia through modulation of adaptive immune cells. J Neuroimmunol. 2011.
  
  
• AA Staniland, AK Clark, R Wodarski, O Sasso, F Maione, F D'Acquisto, M Malcangio: Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice. J Neurochem, 2011, 114:1143-57.

 

 

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