An interview with María Chaparro

Javier P. Gisbert: Investigator-initiated studies (IIS) are clinical studies initiated and managed by non-pharmaceutical company researchers, including individual investigators, institutions, collaborative study groups and cooperative groups. The researcher is responsible for the legal and regulatory responsibilities of the trial sponsor for the conduct and management of the study as defined by all applicable laws and regulations. Your group at La Princesa Hospital (Madrid, Spain) has remarkable experience in this type of study. What attracts you most to such studies?

Francesca Maria Onidi © Francesca Maria Onidi

The award of an N-ECCO Travel Grant, organised by ECCO, enabled me to spend time as an intern in the prestigious Inflammatory Bowel Diseases Centre at Humanitas Research Hospital, the largest IBD centre in Italy. The Centre provides the most innovative treatments and therapeutic strategies for IBD patients in accordance with current scientific evidence and offers a multidisciplinary approach to IBD with the help of industry experts and novel technologies. At the Humanitas outpatient clinic dedicated to IBD, patients are followed by IBD nurse Simona Radice. In addition to the provision of medical assistance to patients, the Centre is strongly engaged in research activities aimed at developing new treatments and diagnostic and/or therapeutic strategies. Participation in clinical trials is subject to a preliminary clinical evaluation during a specialist visit to the Centre.

The role of Nlrp9b in regulating intestinal inflammation  

Danping Zheng © Danping Zheng

Aim of the research

Innate immune signalling pathways, including inflammasome-forming Noll-like receptors (NLR), are thought to mediate the risk of Inflammatory Bowel Disease (IBD) since this system acts as the first line of defence in the recognition of enteric pathogens. In our preliminary study, we identified a new NLR member, Nlrp9b, whose role in the pathogenesis of IBD remains to be clarified. The aim of our study is to investigate the role of Nlrp9b in regulating intestinal inflammation and the underlying mechanisms.

TSG-6, a potential new therapeutic target in fistulising Crohn’s Disease  

Sudharshan Elangovan © Sudharshan Elangovan

Background

Fistulising Crohn’s Disease (CD) represents a demanding, complex, and as yet unresolved issue, characterised by lesions with active pus drainage through the external fistula openings. Despite advances in understanding of the pathophysiology, to date there are no specific and efficient therapies or molecular markers for its treatment or prevention. TNF-α stimulated gene/protein-6 (TSG-6), an anti-inflammatory protein produced in response to signals from injured tissue, has been shown to exert remarkable therapeutic effects on colitis and on wound healing in various disease models.

Monocyte-derived macrophages as crucial players in the resolution of inflammation and tissue repair in Inflammatory Bowel Disease  

Sales Ibiza © Sales Ibiza

Background

Inflammatory Bowel Disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract leading to debilitating symptoms. No curative therapies are currently available for IBD, with the consequence that the disease has a significant impact on the emotional, financial and social status of patients and their families. Although most studies conducted on IBD over the past few decades have investigated abnormal adaptive immunity, the focus has recently shifted towards alterations in innate immune response. Recent data suggest a causal link between defects in the resolution of inflammation associated with impaired bacterial clearance, excessive cytokine secretion and altered monocyte-macrophage (Mφ) transition in patients with IBD.

Deciphering the gut-specific B cell response in Inflammatory Bowel Disease (IBD)  

Mathieu Uzzan © Mathieu Uzzan

Aim of the research

Given that there is a large complement of mucosal B cells that plays a pivotal role in the regulation of the microbiome and in mucosal homeostasis, it is likely that they play an important but yet understudied role in the pathogenesis of IBD. Therefore, we hypothesize that mucosal inflammation as seen in IBD will induce a B cell response with homeostatic and perhaps pathogenic properties.

Investigation of the role of Par4-associated cell polarity and associated barrier defects in Inflammatory Bowel Diseases  

Federica Branchi © Federica Branchi

Aim of the research

In Inflammatory Bowel Diseases (IBD), epithelial barrier defects occur as a consequence of chronic inflammation. Recent research has suggested that cell polarity alterations may be upstream of barrier defects and additionally play a role in IBD-associated carcinogenesis (colitis-associated and small intestinal carcinoma). Par4 is a gene encoding a protein crucial in the development of cell polarity. LKB1, its human homologue, is mutated in Peutz-Jeghers syndrome (PJS), a genetic condition characterised by a higher risk of epithelial cancers. Considering the pivotal role of Par4/LKB1 in the development of epithelial cell polarity, this project aims to assess its involvement in IBD-associated barrier defects and carcinogenesis.

Viktor Domislović  © Viktor Domislović

Cumulative burden of inflammation predicts colorectal neoplasia risk in Ulcerative Colitis: A large single-centre study

Choi CR, Al Bakir I, Ding NJ, Lee GH, Askari A, Warusavitarne J, Moorghen M, Humphries A, Ignjatovic-Wilson A, Thomas-Gibson S, Saunders BP, Rutter MD, Graham TA, Hart AL
Gut. 2017 Nov 17. pii: gutjnl-2017-314190. doi: 10.1136/gutjnl-2017-314190.

Valentina Petito © Valentina Petito

Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in Inflammatory Bowel Disease

Häsler R, Sheibani-Tezerji R, Sinha A, Barann M, Rehman A, Esser D, Aden K, Knecht C, Brandt B, Nikolaus S, Schäuble S, Kaleta C, Franke A, Fretter C, Müller W, Hütt MT, Krawczak M, Schreiber S, Rosenstiel P
Gut. 2017;66:2087–2097. doi:10.1136/gutjnl-2016-311651

Nuha Yassin © ECCO

With the Y-ECCO Interview corner, we travel the world and share the thoughts of some of the most inspirational IBD leaders. Today we travel to Australia in order to share the IBD journey of a very successful and inspirational IBD leader, Professor Jane Andrews, who is head of the IBD service and Education in the Department of Gastroenterology and Hepatology at The Royal Adelaide Hospital in Australia and a clinical professor at the School of Medicine, University of Adelaide.