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MIBRC Research

Principal Investigators:

Bobby Cherayil, MD

Alessio Fasano, MD >>

Verena Göbel, MD

Bryan Hurley, PhD

Hai Ning Shi, DVM, PhD

W. Allan Walker, MD

Collaborators:

Beth McCormick, PhD

Hans-Christian Reinecker, MD

Research Lab

Alessio Fasano, MD>

Director, Mucosal Immunology and Biology Research Center, MGHfC
Director, Center for Celiac Research, MGHfC
Associate Chief for Basic, Clinical and Translational Research, MGHfC
Division Chief, Department of Pediatric Gastroenterology and Nutrition, MGHfC
Visiting Professor of Pediatrics, Harvard Medical School

Phone: 617-724-4604
Fax: 617-726-4172
Email: afasano@partners.org

Research Team

Stefania Senger, Instructor, Pediatrics, Harvard Medical School
Maria Rosaria Fiorentino, Lecturer, Pediatrics, Harvard Medical School
Karen Lammers, Lecturer, Pediatrics, Harvard Medical School
Maureen Leonard, MD, Clinical Fellow

Gloria Serena, Graduate Research Assistant
Craig Sturgeon, Graduate Research Assistant
Jingang Lan, Research Laboratory Manager
Shu Yan, Research Technician

Pathophysiology of the Intestinal Paracellular Pathway

Combining the disciplines of microbiology, molecular and cell biology, and physiology, Dr. Fasano’s research focuses on the crosstalk between enteric pathogens and their hosts. Through his earlier work Dr. Fasano has elucidated various intracellular signaling pathways that govern eukaryotic cell functions.
Through the discovery of a new enterotoxin named Zot (Zonula occludens toxin) in the late 1980s, Dr. Fasano and his colleagues began the study of the mechanism of action that involves the modulation of intercellular “tight junctions.” A series of seminal discoveries clarified that the paracellular space is not completely sealed, as previously believed, but is rather a sophisticated network of proteins forming tight junctions (TJ).

Zonulin Pathway

The discovery of Zot shed light on the modulation of TJ and led to the discovery of several other toxins that affect the paracellular pathway, opening new paradigms for bacterial pathogenesis. Several years later, the Fasano team discovered zonulin, a Zot mammalian analogue involved in the regulation of TJ. Safety and efficacy testing of a zonulin inhibitor, Larazotide acetate, has been completed and phase 2B clinical trials are currently under way.

The Fasano lab has a major research interest in the pathophysiology of the paracelluar pathway and the structural changes of cell cytoskeleton and TJ induced by zonulin, its prokaryotic analogue Zot, and gluten peptides. Research conducted and reviewed by the Fasano group has linked many autoimmune diseases, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, ankylosing sponditis, IgA nephropathy, and inflammatory bowel diseases to the common denominator of aberrant intestinal permeability

Current research directed by Dr. Fasano encompasses both basic science focused on bacterial pathogenesis, gut microbiome and intestinal mucosal biology, and translational science focused on interventional clinical trials in autoimmune and inflammatory diseases, including celiac disease and asthma. Researchers are looking at how qualitative or quantitative defects in the regulation of the immune system and the role of dysbiosis can lead to the onset and progression of celiac disease and other autoimmune disorders. One objective of the Fasano lab is to understand the molecular mechanisms of the host’s functional and immune response to specific microorganisms.
This includes in-depth studies of bacteria-host interactions of three major gram negative bacterial human pathogens, including Helicobacter pylori, Salmonella enterica serovar Typhi, and Shigella dysenteriae-1, each primarily affecting a distinct major segment of the GI tract (i.e., the stomach, ileum and colon, respectively). Using new methodologies to study, in vitro and ex vivo, it is hoped that this interplay between microorganisms and host will shed light on clinical condtions in which this interplay may lead to disease status.

Dr. Fasano moving
Dr. Fasano moves into his new offices at MGH.

 

Through earlier work at the Center for Celiac Research at the University of Maryland School of Medicine, Dr. Fasano established that celiac disease affects approximately one percent of the U.S. population, a significantly higher number than previously believed. Work from the Center for Celiac Research has also recently identified molecular differences between celiac disease and gluten sensitivity, a newly defined condition on the spectrum of gluten-related disorders.

The Fasano lab is currently investigating the composition and changes in the gastrointestinal microbiota to help determine why some individuals with an inherited predisposition to celiac disease develop clinical disease while others do not. International collaborators with the Fasano lab are also investigating the role of the timing of gluten introduction to infants in the development of celiac disease and working to uncover a biomarker and to develop a diagnostic tool for gluten sensitivity. Dr. Fasano is also pursuing possible links between gluten-related disorders and conditions such as schizophrenia and Autism Spectrum Disorder in certain subgroups of patients.