Edward Thomas Ryan | |
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Born | |
Alma mater | Princeton University (A.B.) Harvard University (M.D.) |
Scientific career | |
Institutions | Massachusetts General Hospital Harvard University |
Website | Laboratory Webpage |
Edward Thomas Ryan (born September 5, 1962) is an American microbiologist, immunologist, and physician at Harvard University and Massachusetts General Hospital. Ryan served as president of the American Society of Tropical Medicine and Hygiene from 2009 to 2010. Ryan is Professor of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health, Professor of Medicine at Harvard Medical School, and Director of Global Infectious Diseases at the Massachusetts General Hospital. Ryan's research and clinical focus has been on infectious diseases associated with residing in, immigrating from, or traveling through resource-limited areas. Ryan is a Fellow of the American Society of Microbiology, the American Society of Tropical Medicine and Hygiene, the American College of Physicians, and the Infectious Diseases Society of America.
Ryan's investigative work has focused on tropical, emerging and global infectious diseases, especially understanding host-pathogen interactions, and relating that knowledge to the discovery, development, and implementation of advanced diagnostics and vaccines. Particular areas of focus include cholera, typhoid, shigella, COVID-19 and the transmission of infectious diseases by humans crossing international borders.
Ryan was born in New York City and educated at the Horace Mann School. He received his bachelor's degree in biochemical sciences at Princeton University. He received a doctorate in medicine from Harvard University. He performed medical residency and fellowship training in infectious diseases at the Massachusetts General Hospital. Ryan received additional training at the London School of Hygiene and Tropical Medicine and the International Center for Diarrhoeal Disease Research (ICDDRB) in Dhaka, Bangladesh. Ryan was also an overseas fellow of the Center for the Study of the Society and Medicine, Columbia University College of Physicians and Surgeons. Following his training, Ryan joined the faculty of Harvard University and the staff of the Massachusetts General Hospital. He was appointed Professor at Harvard University in April, 2012. Ryan resides in Wellesley, Massachusetts.
Together with Dr. Stephen Calderwood, Dr. Jason Harris, Dr. Regina LaRocque, Dr. Daniel Leung, Dr. Richelle Charles and colleagues at Harvard, and Dr. Firdausi Qadri and colleagues at the ICDDRB, Ryan has focused on advancing understanding of host-pathogen and immune responses during cholera, a human-restricted infection that largely afflicts impoverished individuals in resource-limited areas of the world. Ryan's investigative work is supported by the U.S. National Institutes of Health. Significant contributions include the finding that contrary to the previously established paradigm, cholera induces a pro-inflammatory response in afflicted humans, and that this response correlates with magnitude and duration of immunity against cholera. [1] [2] [3] Ryan has particularly focused on analyzing immune responses against the polysaccharide coating of the Vibrio cholerae organism, the O-specific polysaccharide (OSP), working with Dr. Paul Kovac of the National Institutes of Health. [4] [5] Immune responses to OSP mediate protection against cholera in humans, [6] and Ryan et al have shown that this protection is associated with the ability of antibodies targeting V. cholerae OSP to inhibit the normally highly mobile bacteria from swimming inside the intestinal lumen. [7] [8] This work has informed advanced vaccine development. [9] [10] [11] Ryan has been awarded a MERIT Award from the NIH in support of these efforts.
Ryan's efforts in typhoid have largely focused on using high throughput analyses to characterize both pathogen responses during typhoid fever, including bacterial gene expression in infected humans, and human immune responses to bacterial infection. [12] [13] [14] This collaborative work with Charles and Qadri has identified a biomarker of chronic carriage of the bacillus that causes typhoid fever (YncE; STY1479), [15] and included the first transcriptional (gene expression) analysis of a bacterial pathogen directly in the bloodstream of an infected human; [16] [17] work that was performed in humans with typhoid and paratyphoid fever in Bangladesh. This work has informed diagnostic assay development. [18] [19]
Ryan's efforts on shigellosis have focused on vaccine development and host-pathogen interactions. [20] [21] In 2006, Ryan showed that administration of antibiotics to children with shigellosis in Bangladesh did not increase toxin production by the bacterium. [22] This finding supports targeted antimicrobial treatment of humans with shigellosis. Such treatment is usually contraindicated in humans infected with Shiga-toxin expressing E. coli infection (STEC/EHEC: enterohemorrhagic E. coli, Verotoxin-producing Escherichia coli), in whom such treatment substantially increasing the risk of renal failure. [23]
Ryan co-directs the Global TravEpiNet (GTEN) consortium and program with Dr. Regina LaRocque. GTEN's focus has been to advance the health of U.S. residents who cross international borders. The GTEN network and its support tools were developed with support from the Centers for Disease Control and Prevention with the goal of lessening illness relating to crossing international borders and the likelihood of disease importation into home communities. This program has included the development of a number of public health programs and resources, including web tools that provide up-to-date recommendations on health interventions and risks; these resources are maintained within the Heading Home Healthy Program. [24]
When the COVID-19 pandemic began, Ryan pivoted his focus to working collaboratively on COVID-19. Efforts included development of an EUA (Expanded Access Authorized) laboratory-based PCR test, development of serologic assays for SARS-CoV-2 (the virus that causes COVID-19), analysis of persistence and decay of human antibody responses in COVID-19 patients, assessment of test performance characteristics of available serological and PCR assays against SARS-CoV-2, development of ultrasensitive antigen and antibody detection systems for SARS-CoV-2, assessment of immunologic cross-reactivity of SARS-CoV-2 with other coronaviridae, assessment of immune responses to SARS-CoV-2 in children, assessment of COVID-19 in Bangladesh, analysis of antibody functionality and signature during SARS-CoV-2 infection in relationship to mortality outcome, comparison of immune responses following vaccination to those induced by SARS-CoV-2 infection, assessment of plasma viral load with severity and mortality, and evaluation of the genomic epidemiology of SARS-CoV-2 in the Boston area. The detailed genomic epidemiology research identified that SARS-CoV-2 was imported repeatedly into the Boston area in early 2020 through international and domestic travel, and that a single superspreading event in Boston was genetically linked to over 300,000 subsequent cases in multiple states and in at least 9 countries in Europe, Asia and Oceania. [25]
Ryan is a staff Physician and Pediatrician at the Massachusetts General Hospital. He is Board certified in both Internal Medicine and Infectious Diseases, and has expertise in global infectious diseases and tropical medicine, including clinical parasitology, virology, bacteriology and mycology. Ryan is the Director of Global Infectious Diseases at Massachusetts General Hospital, and in 2006 isolated a new bacterial species ( Bartonella rochalimae) in the blood of a woman with fever and splenomegaly who had recently been in Peru. The bacterium was characterized with colleagues at the University of California at San Francisco and the Centers for Disease Control and Prevention. [26] Ryan served with the Massachusetts General Hospital field deployment team aboard the USNS Mercy hospital ship in Banda Aceh, Indonesia following the December 26, 2004 Indian Ocean earthquake and tsunami. [27] [28]
Ryan teaches at Harvard College, Harvard Medical School and the Harvard School of Public Health. He trains post-doctoral fellows and students in his laboratory, as well as intern, resident, fellow and student clinicians-in-training at the Massachusetts General Hospital. He directs a Fogarty International Center Training program between the Massachusetts General Hospital and the ICDDRB in Bangladesh.
Ryan has served on advisory and review committees for the National Institutes of Health, the US Centers for Disease Control and Prevention, and the Institute of Medicine.
Ryan has authored or co-authored over 300 publications, including over 200 in the peer-reviewed literature. He also has served in editorial capacities for PLoS Neglected Tropical Diseases, the CDC Yellow Book [29] (Health Information for International Travel), Microbes and Infections, [30] and is Senior Editor of Hunter’s Tropical Infectious Diseases.
Cholera is an infection of the small intestine by some strains of the bacterium Vibrio cholerae. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea lasting a few days. Vomiting and muscle cramps may also occur. Diarrhea can be so severe that it leads within hours to severe dehydration and electrolyte imbalance. This may result in sunken eyes, cold skin, decreased skin elasticity, and wrinkling of the hands and feet. Dehydration can cause the skin to turn bluish. Symptoms start two hours to five days after exposure.
Typhoid fever, also known as typhoid, is a disease caused by Salmonella serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several days. This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting. Some people develop a skin rash with rose colored spots. In severe cases, people may experience confusion. Without treatment, symptoms may last weeks or months. Diarrhea may be severe, but is uncommon. Other people may carry it without being affected, but are still contagious. Typhoid fever is a type of enteric fever, along with paratyphoid fever. S. enterica Typhi is believed to infect and replicate only within humans.
Vibrio cholerae is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimp, and other shellfish. Some strains of V. cholerae are pathogenic to humans and cause a deadly disease called cholera, which can be derived from the consumption of undercooked or raw marine life species.
El Tor is a particular strain of the bacterium Vibrio cholerae, the causative agent of cholera. Also known as V. cholerae biotype eltor, it has been the dominant strain in the seventh global cholera pandemic. It is distinguished from the classic strain at a genetic level, although both are in the serogroup O1 and both contain Inaba, Ogawa and Hikojima serotypes. It is also distinguished from classic biotypes by the production of hemolysins.
Vibrio is a genus of Gram-negative bacteria, possessing a curved-rod (comma) shape, several species of which can cause foodborne infection, usually associated with eating undercooked seafood. Being highly salt tolerant and unable to survive in fresh water, Vibrio spp. are commonly found in various salt water environments. Vibrio spp. are facultative anaerobes that test positive for oxidase and do not form spores. All members of the genus are motile. They are able to have polar or lateral flagellum with or without sheaths. Vibrio species typically possess two chromosomes, which is unusual for bacteria. Each chromosome has a distinct and independent origin of replication, and are conserved together over time in the genus. Recent phylogenies have been constructed based on a suite of genes.
In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization.
An asymptomatic carrier is a person or other organism that has become infected with a pathogen, but shows no signs or symptoms.
A conjugate vaccine is a type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.
Pneumococcal vaccines are vaccines against the bacterium Streptococcus pneumoniae. Their use can prevent some cases of pneumonia, meningitis, and sepsis. There are two types of pneumococcal vaccines: conjugate vaccines and polysaccharide vaccines. They are given by injection either into a muscle or just under the skin.
The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome. One component is known as the A subunit, and the remaining five components are B subunits. All of these toxins share a similar structure and mechanism for entering targeted host cells. The B subunit is responsible for binding to receptors to open up a pathway for the A subunit to enter the cell. The A subunit is then able to use its catalytic machinery to take over the host cell's regular functions.
Orientia tsutsugamushi is a mite-borne bacterium belonging to the family Rickettsiaceae and is responsible for a disease called scrub typhus in humans. It is a natural and an obligate intracellular parasite of mites belonging to the family Trombiculidae. With a genome of only 2.0–2.7 Mb, it has the most repeated DNA sequences among bacterial genomes sequenced so far. The disease, scrub typhus, occurs when infected mite larvae accidentally bite humans. Primarily indicated by undifferentiated febrile illnesses, the infection can be complicated and often fatal.
The discovery of disease-causing pathogens is an important activity in the field of medical science. Many viruses, bacteria, protozoa, fungi, helminthes and prions are identified as a confirmed or potential pathogen. In the United States, a Centers for Disease Control program, begun in 1995, identified over a hundred patients with life-threatening illnesses that were considered to be of an infectious cause, but that could not be linked to a known pathogen. The association of pathogens with disease can be a complex and controversial process, in some cases requiring decades or even centuries to achieve.
The seventh cholera pandemic is the seventh major outbreak of cholera and occurred principally from the years 1961 to 1975, but the strain involved persists to the present. WHO and some other authorities believe this should be considered as an ongoing pandemic. As stated in its cholera factsheet dated 30 March 2022, the World Health Organization (WHO) continues to define this outbreak as a current pandemic, and with cholera having become endemic in many countries. In 2017, WHO announced a global strategy aiming to end this pandemic by 2030.
The CTXφ bacteriophage is a filamentous bacteriophage. It is a positive-strand DNA virus with single-stranded DNA (ssDNA).
Firdausi Qadri is a Bangladeshi scientist with specialization in immunology and infectious disease research. She has worked over 25 years on the development of vaccines for cholera and has expertise on other infectious disease like ETEC, Typhoid, Helicobacter pylori, rotavirus, etc. Currently, she is working as a director for Centre for Vaccine Sciences of International Centre for Diarrhoeal Disease and Research, Bangladesh (ICDDR,B). She also serves as chairperson of the Institute for developing Science and Health initiatives. Her scientific achievements lie in enteric infections and vaccines including Vibrio cholerae and enterotoxigenic Escherichia coli—major causes of severe diarrhea. She has also focused on studying the immune response in Helicobacter pylori infected people in Bangladesh and the responses in patients with typhoid fever as well as vaccinees. The Government of Bangladesh awarded her the Independence Award in 2023.
Ira M. Longini is an American biostatistician and infectious disease epidemiologist.
Nirmal Kumar Dutta (1913–1982) was an Indian pharmacologist, medical academic and the director of Haffkine Institute, Mumbai. He was known for his contributions to the studies on cholera and was an elected fellow of the National Academy of Medical Sciences, National Academy of Sciences, India and the Indian National Science Academy. The Council of Scientific and Industrial Research, the apex agency of the Government of India for scientific research, awarded him the Shanti Swarup Bhatnagar Prize for Science and Technology, one of the highest Indian science awards for his contributions to Medical Sciences in 1965.
John Glenn Morris, Jr. is an American physician and epidemiologist. He is the founding and current director of the Emerging Pathogens Institute, an interdisciplinary research facility located within the University of Florida, having served since 2007.
Melanie Blokesch is a German microbiologist. Her research focuses on Vibrio cholerae, the bacterium causing cholera. She is a professor of life sciences at École Polytechnique Fédérale de Lausanne (EPFL), where she heads the Laboratory of Molecular Microbiology.
Jan Roland Holmgren is a Swedish physician, microbiologist, immunologist, and vaccinologist, known for his research on cholera and mucosal immunology, specifically, for his leadership in developing "the world's first effective oral cholera vaccine".