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Our research focuses on host-bacterial pathogen interactions and immune responses, with a particular focus on enteric infections and the development of vaccines protective against enteric infections, and development of diagnostic assays. Specific focus areas include Vibrio cholerae, the cause of cholera, and Salmonella enterica, the causes of typhoid and paratyphoid fever. We work in collaborative efforts with researchers at the International Centre for Diarrhoeal Disease Research in Dhaka Bangladesh (ICDDR,B).
Our laboratory is comprised of four post-doctoral fellows, three technicians, and two students.
Edward T. Ryan, M.D. is the Director of Global Infectious Diseases at Massachusetts General Hospital, Professor of Medicine at Harvard Medical School, and Professor of Immunology and Infectious Diseases at Harvard School of Public Health. Dr. Ryan received his Bachelor’s degree in Biochemical Sciences from Princeton University, and a Doctorate in Medicine from Harvard University. He performed medical residency and fellowship training in infectious diseases at Mass General. Dr. Ryan received additional training in tropical medicine and infectious diseases at the London School of Hygiene & Tropical Medicine, was a Fellow in Human Rights & Medicine, Columbia University, and was an International Fellow, International Centre for Diarrhoeal Disease Research (ICDDR, B), Dhaka, Bangladesh.
Dr. Ryan's research focuses on clinical studies of illnesses associated with residing in, immigrating from, or traveling through resource-limited settings. His research is funded by the U.S. National Institute of Allergy and Infectious Diseases (NIAID) and the U.S. Centers for Disease Control & Prevention (CDC). Dr. Ryan is the principal investigator on research projects focusing on enteric vaccine development, host-pathogen studies on V. cholerae (the cause of cholera) and Salmonella enterica serovar Typhi (the cause of typhoid fever). Particular areas of focus include the application of high throughput genomic, proteomic, immunoproteomic, and web-based platform technologies to these illnesses. Dr. Ryan is also the Director of Global TravEpiNet, a CDC-supported national consortium focusing on global infectious diseases and evaluating vaccination strategies and use among global international travelers. He is the principal investigator and program director for a Fogarty International Center, National Institutes of Health (NIH)-sponsored Training Program in Vaccine Development and Public Health between Harvard, Mass General and the ICDDR,B in Dhaka, Bangladesh. Dr. Ryan teaches tropical medicine and infectious diseases in the core curricula at Harvard Medical School, Harvard T.H. Chan School of Public Health and Harvard College, teaches students, residents and fellows at Mass General, and teaches in a number of post-graduate courses at Harvard Medical School and internationally.
Dr. Ryan has served on expert and advisory committees for the Institute of Medicine-National Academy of Sciences, U.S. Centers for Disease Control & Prevention, chaired the Clinical Research and Field Studies of Infectious Diseases Study section of the US NIH from 2006-2008, currently chairs the Standards and Treatment Guidelines Committee of the American Society of Tropical Medicine & Hygiene (ASTMH), and served as ASTMH President from 2009-2010. Dr. Ryan has been elected to Fellowship of the American College of Physicians, the Infectious Diseases Society of America, the American Society of Tropical Medicine & Hygiene, and the American Academy of Microbiology, and has published over 200 peer-reviewed journal articles and book chapters on enteric infections, infectious diseases, vaccines, and tropical medicine. Dr. Ryan is a Senior Editor of Hunter's Tropical Medicine, 9th Edition.
In a collaborative effort with researchers at the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh (ICDDR,B), we are evaluating immune responses in humans infected with Vibrio cholerae, the cause of cholera. V. cholerae is endemic in over 50 countries, infects approximately 3-5 million individuals globally, and results in the death of approximately 100,000 individuals each year. Individuals most affected by cholera are those most impoverished, especially those lacking safe water and sanitary facilities, as well as individuals displaced by war, famine, disasters, and conflict. Cholera can be explosively epidemic, and the global burden of cholera may well increase with climate change, severe weather events, and increasing urbanization. V. cholerae is a human-restricted infection, and current cholera vaccines provide relatively short-term protection against disease. The mediators of protective immunity against cholera are poorly understood. To address this, we are applying a number of high throughput and platform technologies to assess innate and adaptive immune responses in humans with cholera and their household contacts, stratifying responses in the latter by subsequent protection from disease, and comparing responses in the former to those that occur in recipients of current cholera vaccines. The goal of these studies is to identify the mediators of protection against cholera, in order to advance improved prevention strategies, as well as to advance vaccine development and deployment.
In a collaborative effort with researchers at the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh (ICDDR,B), we are evaluating host-pathogen interactions and immune responses in humans infected with Salmonella enterica serotype Typhi (the cause of typhoid fever) and S. Paratyphi (the cause of paratyphoid fever). Together, S. Typhi and S. Paratyphi cause approximately 20 million cases of enteric fever world-wide, resulting in approximately 200,000 deaths each year. Most of these deaths occur in impoverished children and young adults. Although usually caused by S. Typhi, one in four cases of enteric fever is caused by S. Paratyphi in many areas of the world. S. Typhi and S. Paratyphi are particularly common among urban residents in informal settlements and slums, although any individual lacking safe water and sanitary facilities is at risk of infection. Vaccines against S. Typhi provide only 50-60% protection against disease for 2-5 years, and, at present, there is no commercially available vaccine against S. Paratyphi. There is also no good point-of-care test to diagnose individuals with enteric fever, and S. Typhi and S. Paratyphi are becoming increasingly resistant to antimicrobial agents.To address this, we are evaluating host-pathogen interactions directly in humans infected with S. Typhi and S. Paratyphi. We are applying a number of technologies to evaluate innate and adaptive immune responses directly in humans infected with S. Typhi and S. Paratyphi in Bangladesh, and we are evaluating bacterial responses in humans during these human-restricted infections. The goal of these studies is to develop improved diagnostic assays, antimicrobial agents, and preventative strategies against these infections.
A fundamental challenge facing many enteric and mucosal vaccines is their inability to induce long-term protective immunity. Many of these vaccines may not be prominent inducers of memory cells, which play critical roles in mediating long-term protection against disease. Using our analysis of memory B and T cell induction during wild-type human enteric infection in Bangladesh, we are evaluating the ability of a number of vaccination approaches and strategies to induce long-term memory responses protective against mucosal and enteric infections, including development of enteric conjugate vaccines, and analysis of oral-transcutaneous prime-boosting approaches.
To extend our analysis of infections associated with living in, traveling through, or immigrating from resource-limited areas, we also work with the U.S. Centers for Disease Control and Prevention through the GTEN (Global TravEpiNet; Global Travelers’ Epidemiology Network) Program. GTEN’s mission is to advance the health of American residents who travel internationally, as well as to lessen the likelihood of disease importation into home communities. GTEN-relate resources are available at Heading Home Healthy
Edward T. Ryan, MD
Massachusetts General Hospital
Lucia Pizzo FlahertyAdministrative CoordinatorEmail
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