Plenary Speakers

A Plenary Lecture is featured on both Monday and Tuesday mornings during the ACT Annual Meeting. The Program Committee has selected interesting and timely speakers for the ACT Annual Meeting Plenary Lectures.

Monday, November 18, 8:00 AM–8:55 AM

Alessio Fasano, MD

W. Allan Walker Chair, Pediatric Gastroenterology and Nutrition
Chief, Division of Pediatric Gastroenterology and Nutrition
Director, Center for Celiac Research and Treatment
Director, Mucosal Immunology and Biology Research Center
Associate Chief, Department of Pediatrics, Basic, Clinical and Translational Research
MassGeneral Hospital for Children
Professor of Pediatrics, Harvard Medical School
Professor of Nutrition, Harvard T.H. Chan School of Public Health

Alessio Fasano, MD, is a professor of pediatrics at Harvard Medical School and the director of the Mucosal Immunology and Biology Research Center at MassGeneral Hospital for Children (MGHfC). Dr. Fasano’s current research expertise encompasses basic science focused on bacterial pathogenesis, gut microbiome composition and function in health and disease, the regulation of gut permeability, and intestinal mucosal biology and immunology, as well as translational science focused on the role of impaired intestinal barrier function in the pathogenesis of autoimmune and inflammatory diseases, including celiac disease and type 1 diabetes.

In 2000, Dr. Fasano’s group was responsible for the discovery of zonulin, a protein involved in the regulation of tight junctions that is released in conditions of dysbiosis. The director of the Center for Celiac Research and Treatment at MGHfC, Dr. Fasano is also the author of Gluten Freedom. Dr. Fasano is widely sought after as an expert in celiac disease, intestinal permeability, and autoimmune disorders.

Abstract

Title: The Healing Power of Nutrition: How Diet Can Reshape the Gut Microbiome and Influence the Balance between Health and Disease

Description: Improved hygiene leading to a reduced exposure to microorganisms has been implicated as one possible cause for the recent “epidemic” of chronic inflammatory disease (CID) in industrialized countries. This is the essence of the hygiene hypothesis that argues that the rising incidence of CID may be, at least in part, the result of lifestyle and environmental changes that have made us too “clean” for our own good. Apart from genetic makeup and exposure to environmental triggers, three more elements have recently been identified as key players in the pathogenesis of autoimmunity. A third element, the inappropriate increase in intestinal permeability, which may be influenced by the composition of the gut microbiota, has been proposed. The immune system responsible for the tolerance-immune response represents the fourth element involved in the pathogenesis of CID. Finally, the composition of the gut microbiome and its epigenetic influence on the host genomic expression has been identified as a fifth element in causing CID.

The gut microbiome consists of more than 100 trillion microorganisms, most of which are bacteria. It has just recently been recognized that there is a close bidirectional interaction between the gut microbiome and our immune system, and this cross talk is highly influential in shaping the host’s gut immune system function and, ultimately, shifting genetic predisposition to clinical outcome. This observation has led to a revisitation of the possible causes of the CID epidemic, suggesting a key pathogenic role of microbiome composition. While factors such as modality of birth delivery, neonatal feeding regimens, infections, and use of antibiotics can influence microbiota composition, diet is by far the most important variable affecting the gut ecosystem. Therefore, reshaping gut microbiota through dietary manipulation is becoming an extremely active area of research for the prevention or treatment of a multitude of CIDs.

Tuesday, November 19, 8:00 AM–8:55 AM

Thomas Hartung, MD, PhD

Director, Center for Alternatives to Animal Testing (CAAT)
Professor, Evidence-Based Toxicology
Joint Appointment: Department of Molecular Microbiology and Immunology
Johns Hopkins University Center for Alternatives to Animal Testing
Director, CAAT-Europe
Professor for Pharmacology and Toxicology
University of Konstanz, Germany

Thomas Hartung, MD, PhD, is the Doerenkamp-Zbinden Chair for Evidence-Based Toxicology with a joint appointment for Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. He holds a joint appointment as a professor for pharmacology and toxicology at the University of Konstanz in Germany. Dr. Hartung also is the director of the Center for Alternatives to Animal Testing (CAAT) of both universities. CAAT hosts the secretariat of the Evidence-Based Toxicology Collaboration, the Good Read-Across Practice Collaboration, the Good Cell Culture Practice Collaboration, the Green Toxicology Collaboration, and the Industry Refinement Working Group. As PI, Dr. Hartung headed The Human Toxome Project, funded as a National Institutes of Health Transformative Research Grant. He is the former head of the European Centre for the Validation of Alternative Methods (ECVAM) in Ispra, Italy, and has authored more than 550 scientific publications.

Abstract

Title: From Microphysiological to Micropathophysiological Models

Description: Organotypic cell culture of spheroids and organ- and human-on-chip technologies is a disruptive approach increasingly enabling the replacement of animal studies with healthy human tissues and their combinations. At the same time, the shortcomings of traditional animal tests, with respect to costs, duration, throughput, and human relevance, are increasingly recognized.

Major parts of the (developmental) biology can now be recapitulated, especially in human stem cell-derived models. In combination with computational approaches, acute and topical toxicities can be tackled, and an increasing number of animal-free OECD test guidelines is available. The real challenge, however, are the systemic toxicities (repeat-dose organ toxicities, reproductive toxicity, and cancer) and drug development. We need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us in modeling these systems using bioengineering and virtual computer models (i.e., via systems biology or systems toxicology approaches). Experimental multi-organ-on-chip and microphysiological systems (MPS) provide a more physiological view of the organism, facilitating more comprehensive coverage of systemic toxicities (i.e., the perturbation on the organism level) without using substitute organisms (animals). The next challenge is to establish disease models (i.e., micropathophysiological systems [MPPS]) to expand their utility to encompass biomedicine and especially drug development. Combining computational and experimental systems approaches and the challenges of validating them are being discussed. The suggested 3S approach promises to leverage 21st-century technology and systematic thinking to achieve a paradigm change in studying systemic effects.