santos_new

2010 Research Award Recipient

Principle Investigator: Javier Santos Vicente, MD

Hospital Vall d’Hebron
Barcelona, Spain

Dr. Santos graduated in Medicine at the University of Navarra, Spain. He then trained in clinical gastroenterology and obtained the Degree of Gastrointestinal Specialist at Hospital General Universitario Vall d’Hebron, Barcelona, Spain. In parallel, he completed predoctoral studies in basic and clinical research in neurogastroenterology, at the Digestive Diseases Research Unit, Department of Gastroenterology Hospital Vall d’Hebron, and obtained his Ph.D. from the Autonomous University of Barcelona. and later he moved for a 3-year postdoctoral stage in immunology and gastrointestinal physiology, to the Intestinal Disease Research Program, McMaster University, Canada.

His research in the field of neuro-immune-gastroenterology remains inherently transational, with special focus in mechanisms linking genetic, molecular, cellular, and environmental determinants to clinical manifestations of the irritable bowel syndrome and other functional gi disorders. His research also pursues the identification of sensitive and specific biological markers potentially useful for implementing diagnostic and therapeutic management of those disorders.

Dr Santo’s scientific contribution includes dozens of original manuscripts, reviews and editorials in top peer-reviewed journals, and numerous communications/abstracts/lectures in relevant meetings in the field. Dr. Santos has been awarded by the Association of National European and Mediterranean Societies of Gastroenterology as a 2003 European Rising Star of Gastroenterology, and recently by the International Foundation of Functional Gastrointestinal Disorders with the 2009 IFFGD Junior Investigator Research Award in Clinical Science, for his contributions to the field of functional GI disorders.

Role of mucosal eosinophils in the physiopathology of intestinal inflammationin
irritable bowel syndrome

Background: Irritable bowel syndrome (IBS) is the most common functional disorder of the gastrointestinal tract. Its unclear pathophysiology and the lack of specific diagnostic markers and effective therapeutic options determine a remarkable impairment in the quality of life of patients and a growing sanitary burden. Although its nature is reckoned as multifactorial, growing evidence supports the role of stress and gastrointestinal infections in the initiation and development of intestinal mucosal inflammation and barrier dysfunction, providing a putative yet reasonable pathophysiological link to explain visceral hypersensitivity and distorted bowel patterns. Mast cells and lymphocytes are frequently involved; however, the contribution of other immunocytes to this process is unknown.

The eosinophil, a multipotent resident of the gastrointestinal mucosa, displays extensive regulatory ability to promote or balance mucosal inflammation. Apart from primary eosinophylopathies and IBD, increased eosinophil numbers and mediators have been described in other gastrointestinal disorders of diverse etiology (allergic, infectious, vascular, autoimmune and tumoral). We have previously shown enhanced luminal release of eosinophilic cationic protein (ECP), eotaxin and RANTES in the jejunum of IBS patients, after peripheral corticotropin-releasing factor administration, suggesting stress-related eosinophil activation.

Aims: We aim to extend current knowledge on eosinophil contribution in the pathophysiology of Rome III-based IBS.

Methods: We will obtain jejunal biopsies from IBS fulfilling Rome III criteria and healthy volunteers, in which eosinophil-related gene and protein profile, and eosinophil ultrastructure and cell-to-cell interactions will be studied by molecular and electron microscopy techniques. Neurohormonal mechanisms (corticotropin-releasing factor, mast cell and eosinophil mediators, adrenergic/cholinergic receptors) involved in the development of mucosal inflammation will be investigated in jejunal biopsies and eosinophil cultures.santos_new