MRC Centre for Inflammation Research
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Professor Adriano G Rossi

Adriano Rossi's lab aims to gain a better understanding of the mechanisms controlling inflammatory processes with a view to help develop novel therapies for chronic inflammatory diseases.

Professor Adriano Rossi

Chair of Respiratory and Inflammation Pharmacology

  • MRC Centre for Inflammation Research
  • Research Theme: Tissue remodelling and regeneration, Imaging Inflammation

Contact details

Group Members

  • Rodger Duffin - MRC Senior Lecturer/Academic Fellow in Respiratory Medicine
  • John A Marwick - Senior Postdoctoral Research Fellow
  • Tiina Kipari - MRC Postdoctoral Scientist
  • Sara F Rinaldi - Postdoctoral Scientist with Professor Jane Norman
  • Christopher D Lucas - Clinical Lecturer
  • David A Dorward - Clinical Lecturer and PhD training fellow (STMTI scheme): co-supervisors are Dr Kev Dhaliwal and Professor Chris Haslett
  • Jorine Willems - PhD student co-supervised with Professor Chris Gregory (primary supervisor)
  • Laura Hoodless - MRC PhD student co-supervised with Dr Carl Tucker
  • Greg Armstrong - MRC PhD student co-supervised with Professor Hilary Critchley (primary supervisor))
  • Pallavi Mandal - PhD training fellow co-supervised with Dr Adam Hill (primary supervisor) and Dr Donald Davidson
  • Manjit Sidhu - Clinical Research Fellow co-supervised by Dr Adam Hill (primary supervisor)
  • Jillian Rennie - Research Assistant
  • Calum Robb - Research Assistant
  • Amanda Croasdell - Postdoc Research Fellow
  • Magdalena Oremek - PhD student
  • Philippe Potey - PhD student
  • Simone Arienti - MRes student
  • Giulia Rinaldi - MRes student

Background

Aims

We aim to gain a better understanding of the mechanisms controlling inflammatory processes with a view to help develop novel therapies for chronic inflammatory diseases. For this we aim to elucidate the mechanism regulating inflammatory cell behaviour and apoptosis and manipulate the processes controlling the resolution of inflammation in order to develop new therapeutic strategies to remove unwanted and dysregulated inflammation.

Background

Although neutrophilic and eosinophilic granulocytes are key effector cells in host defence against invading bacteria and parasites, over-recruitment, uncontrolled activation and defective removal by macrophages of these cells plays a prominent role in the initiation and propagation of chronic inflammatory conditions including, emphysema, bronchitis, rheumatoid arthritis, inflammatory bowel disease, asthma, etc.  Apoptosis or programmed cell death is a fundamental process regulating inflammatory cell survival providing an efficient non-inflammatory mechanism for removal of potentially histotoxic cells from inflamed sites by resident or recruited macrophages and is critically involved in the successful resolution of inflammation. 

Approaches and Progress

My group has been investigating how neutrophil and eosinophil apoptosis as well as macrophage phagocytosis of apoptotic cells can be regulated by pharmacological intervention, and we believe that selective interference of these fundamental processes may be harnessed for therapeutic gain. Signalling pathways, including those involving transcription factors (eg, NF-kB) and kinases (eg, MAPK and PI3K) have been shown by my research team to be key regulators of inflammatory cell survival and apoptosis in vitro. In addition, we have demonstrated that manipulation of such pathways in vivo has indicated that they also play a role in the resolution of inflammation. Furthermore, we have shown that anti-inflammatory glucocorticoids dramatically enhance the capability of macrophage to phagocytose apoptotic granulocytes and are currently investigating how other mediators of inflammation regulate this process.   Furthermore, we have shown that manipulation of proteins directly involved in the control of apoptosis, such as Bcl-2 family members and caspases, can also be targeted in vivo to influence inflammatory resolution. Recently we have shown that cyclin-dependent kinase (CDK) inhibitor drugs, under development for the treatment of cancer, induce caspase-dependent human neutrophil apoptosis possibly by altering levels of the anti-apoptotic Bcl-2 family member, Mcl-1. Importantly, we have provided evidence that CDK inhibitor drugs augment the resolution of established 'neutrophil dominant' models of inflammation (including pleurisy, pulmonary fibrosis and arthritis) by promoting apoptosis of neutrophils. Thus we believe that manipulation of apoptotic pathways together with ensuring macrophage clearance of apoptotic cells appear to be viable pharmacological targets for reducing established inflammation.  Our approach to understanding the molecular mechanisms governing inflammatory cell function and the resolution of inflammation involves an integrated in vitro, in vivo and translational strategy using wide-ranging technologies.

Research Overview

Inflammatory diseases and especially inflammatory lung diseases like chronic bronchitis and emphysema (COPD) and scarring conditions are responsible for a huge burden of illness and untimely deaths in the UK, but current treatments are at best poorly-effective. Over the past 20 years we have been taking an alternative approach to harness the mechanisms by which some inflammatory responses are known to get better spontaneously. Specifically we have identified a mechanism by which key inflammatory cells called neutrophils can be made to 'commit suicide' and be removed silently by local scavenger cells called macrophages. Unfortunately this suicide process is usually overcome by powerful survival factors present in the inflamed lung. In work newly-published in the leading international medical science journal 'Nature Medicine' we have shown that a CDK inhibitor called R-roscovitine, currently under clinical trial in cancer patients, causes a hitherto unexpected induction of  neutrophil suicide, even in the presence of survival factors, and makes relevant models of human inflammatory lung disease resolve. This work has recently been publicised in the lay press. A part of our proposed programme of research will define exactly how drugs such as R-roscovitine works, an approach which may lead to the discovery of other useful anti-inflammatory drugs. We will also in the processes of carrying out a clinical study of the drug's effectiveness using cutting-edge imaging technology to monitor the progress of the disease non-invasively and demonstrate its response to treatment.

Alumni

  • Dr Andy Conway Morris: Clinical Lecturer in Critical Care
  • Dr A Leticia Alessandri: Postdoctoral Fellow
  • Dr Debbie A Sawatzky: visiting Postdoctoral Fellow
  • Dr Joanna Murray: Postdoctoral Fellow
  • Dr Carol Ward: PhD student and Postdoctoral Fellow
  • Dr Annemieke Walker: Postdoctoral Fellow
  • Dr Emma L Taylor: PhD student and Postdoctoral Fellow
  • Dr Sarah Fox: PhD student and Postdoctoral Fellow
  • Dr Michela Festa: visiting Postdoctoral Fellow
  • Dr Keith E Norman: PhD student
  • Dr Joanne M Cousin: PhD student
  • Dr Morag C Martin: PhD student
  • Dr Satoko Fujihara: PhD student
  • Dr Lorna A Murray: PhD training fellow
  • Dr Sylwia Michlewska: PhD student
  • Dr Andrew E Leitch: PhD Training Fellow
  • Dr Nicola Riley: PhD student
  • Dr Katy I Mecklenburgh: PhD student (primary supervisor Professor Edwin Chilvers)
  • Dr Katherine M Giles: PhD student (primary supervisor Professor Ian Dransfield)
  • Dr Michael S Crane: PhD student (primary supervisor Professor Ian Megson)
  • Dr Catherine A Shaw: PhD student (primary supervisor Professor Ian Megson)
  • Dr Louise Dickson: PhD student (primary supervisor Dr Keith Finlayson)
  • Dr Catriona M Turnbull (nee Scott): PhD student (primary supervisor Professor Ian Megson)
  • Dr Marta Pasikowska: PhD student (primary supervisor Professor Chris Gregory)
  • Dr Irini Bournazou: PhD student (primary supervisor Professor Chris Gregory)
  • Dr Megan Mowbray: MD training fellow (primary supervisor Dr Richard Weller)
  • Dr Hsin-Ni Li: PhD student (primary supervisor Dr Donald Davidson)
  • Dr Michelle L LeBrocq: PhD student (primary supervisor Professor Ian Megson)
  • Dr Mark Nixon: PhD student (primary supervisor Dr Ruth Andrews)
  • Dr Gabrielle Montanaro: visiting PhD student (primary supervisors Professors Alberto Gasco and Roberta Fruttero)
  • Dr Paolo Marcarino: visiting PhD student (primary supervisors Professors Alberto Gasco and Roberta Fruttero)
  • Dr Shalini Rajagopal: PhD student co-supervised with Professor Jane Norman (primary supervisor))
  • Dr Gareth Tomlinson: PhD student (primary supervisor Dr Mohini Gray) 
  • Dr David Griffith: MD Training Fellow co-supervised with Professor Tim Walsh (primary supervisor))
  • Miss Tara A Sheldrake: Research Assistant

Sources of Funding

More information on funding at Adriano Rossi's Research Explorer profile.