Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:
BETHESDA, Md. (AP) — Sam Srisatta, a 20-year-old Florida college student, spent a month living inside a government hospital here last fall, playing video games and allowing scientists to document every morsel of food that went into his mouth.
From big bowls of salad to platters of meatballs and spaghetti sauce, Srisatta noshed his way through a nutrition study aimed at understanding the health effects of ultraprocessed foods, the controversial fare that now accounts for more than 70% of the U.S. food supply. He allowed The Associated Press to tag along for a day.
“Today my lunch was chicken nuggets, some chips, some ketchup,” said Srisatta, one of three dozen participants paid $5,000 each to devote 28 days of their lives to science. “It was pretty fulfilling.”
Examining exactly what made those nuggets so satisfying is the goal of the widely anticipated research led by National Institutes of Health nutrition researcher Kevin Hall.
“What we hope to do is figure out what those mechanisms are so that we can better understand that process,” Hall said.
National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has selected Rena N. D’Souza, D.D.S., M.S., Ph.D., as director of NIH’s National Institute of Dental and Craniofacial Research (NIDCR). A licensed dentist, Dr. D’Souza is currently the assistant vice president for academic affairs and education for health sciences at the University of Utah, Salt Lake City. There she also serves as a professor of dentistry, the Ole and Marty Jensen Chair of the School of Dentistry and professor of neurobiology and anatomy, pathology and surgery in the School of Medicine and the Department of Biomedical Engineering. She is expected to begin her new role as the NIDCR director later this year.
“Dr. D’Souza is renowned for her research in craniofacial development, genetics, tooth development and regenerative dental medicine. She has worked as a proponent for NIH for decades, serving on critical advisory committees and as an expert consultant on multiple projects,” said Dr. Collins. “I look forward to having her join the NIH leadership team later this year. I also want to thank NIH Principal Deputy Director Lawrence A. Tabak, D.D.S., Ph.D., for his valuable leadership as the acting director of NIDCR since January 1, 2020.”
As NIDCR director, Dr. D’Souza will oversee the institute’s annual budget of over $475 million, which supports basic, translational and clinical research in areas of oral cancer, orofacial pain, tooth decay, periodontal disease, salivary gland dysfunction, craniofacial development and disorders and the oral complications of systemic diseases. The institute funds approximately 770 grants, 6,500 researchers and 200 organizations. Additionally, NIDCR supports research training and career development programs for approximately 350 people at various stages of their careers, from high school students to independent scientists.
According to a new study, mortality rates from the most common lung cancer, non-small cell lung cancer (NSCLC), have fallen sharply in the United States in recent years, due primarily to recent advances in treatment.
The study was led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The findings were published August 12, 2020, in the New England Journal of Medicine.
“Reduced tobacco consumption in the U.S. has been associated with a progressive decrease in lung cancer deaths that started around 1990 in men and around 2000 in women. Until now, however, we have not known whether newer treatments might contribute to some of the recent improvement,” said Douglas R. Lowy, M.D., NCI deputy director and co-author of this study. “This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, non-small cell lung cancer, are declining faster than its incidence, an advance that correlates with the U.S. Food and Drug Administration approval of several targeted therapies for this cancer in recent years.”
National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has selected Lindsey A. Criswell, M.D., M.P.H., D.Sc., as director of NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). A rheumatologist, Dr. Criswell is currently the vice chancellor of research at the University of California, San Francisco (UCSF). She is a professor of rheumatology in UCSF’s Department of Medicine, as well as a professor of orofacial sciences in its School of Dentistry. She is expected to begin her new role as the NIAMS director in early 2021. She will succeed long-time director Stephen I. Katz, M.D., Ph.D., who passed away suddenly in December 2018.
“Dr. Criswell has rich experience as a clinician, researcher and administrator. Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well-positioned to direct NIAMS,” said Dr. Collins. “I look forward to having her join the NIH leadership team early next year. I also want to thank Robert H. Carter, M.D., for his exemplary work as the acting director of NIAMS since December 2018.”
As NIAMS director, Dr. Criswell will oversee the institute’s annual budget of nearly $625 million, which supports research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases. The institute advances health through biomedical and behavioral research, research training and dissemination of information on research progress in these diseases.
Vaccine currently being evaluated in Phase 3 clinical testing
The investigational vaccine known as mRNA-1273 protected mice from infection with SARS-CoV-2, the virus that causes COVID-19, according to research published today in Nature. Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the biotechnology company Moderna, based in Cambridge, Massachusetts, along with collaborators from the University of North Carolina at Chapel Hill, Vanderbilt University Medical Center in Nashville, and the University of Texas at Austin conducted the preclinical research. NIAID Vaccine Research Center (VRC) scientists worked with investigators from the University of Texas at Austin to identify the atomic structure of the spike protein on the surface of the novel coronavirus. This structure was used by VRC and Moderna in the development of the vaccine candidate.
The findings show that the investigational vaccine induced neutralizing antibodies in mice when given as two intramuscular injections of a 1-microgram (mcg) dose three weeks apart. Additional experiments found that mice given two injections of the 1-mcg dose and later challenged with SARS-CoV-2 virus either 5 or 13 weeks after the second injection were protected from viral replication in the lungs and nose. Importantly, mice challenged 7 weeks after only a single dose of 1 mcg or 10 mcg of mRNA-1273 were also protected against viral replication in the lung.
Cells heavily infected with SARS-COV-2 virus particles (orange), isolated from a patient sample.
Discovery provides new target for anti-malaria treatments
Researchers at the National Institutes of Health and other institutions have discovered another set of pore-like holes, or channels, traversing the membrane-bound sac that encloses the deadliest malaria parasite as it infects red blood cells. The channels enable the transport of lipids — fat-like molecules — between the blood cell and parasite, Plasmodium falciparum. The parasite draws lipids from the cell to sustain its growth and may also secrete other types of lipids to hijack cell functions to meet its needs.
The finding follows an earlier discovery of another set of channels through the membrane enabling the two-way flow of proteins and non-fatty nutrients between the parasite and red blood cells. Together, the discoveries raise the possibility of treatments that block the flow of nutrients to starve the parasite.
Colorized scanning electron micrograph of red blood cell infected with malaria parasites, which are colorized in blue. The infected cell is in the center of the image area. To the left are uninfected cells with a smooth red surface.
Two doses of an experimental vaccine to prevent coronavirus disease 2019 (COVID-19) induced robust immune responses and rapidly controlled the coronavirus in the upper and lower airways of rhesus macaques exposed to SARS-CoV-2, report scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. SARS-CoV-2 is the virus that causes COVID-19.
The candidate vaccine, mRNA-1273, was co-developed by scientists at the NIAID Vaccine Research Center and at Moderna, Inc., Cambridge, Massachusetts. The animal study results published online today in the New England Journal of Medicine complement recently reported interim results from an NIAID-sponsored Phase 1 clinical trial of mRNA-1273. The candidate mRNA-1273 vaccine is manufactured by Moderna.
In this study, three groups of eight rhesus macaques received two injections of 10 or 100 micrograms (µg) of mRNA-1273 or a placebo. Injections were spaced 28 days apart. Vaccinated macaques produced high levels of neutralizing antibodies directed at the surface spike protein used by SARS-CoV-2 to attach to and enter cells. Notably, say the investigators, animals receiving the 10-µg or 100-µg dose vaccine candidate produced neutralizing antibodies in the blood at levels well above those found in people who recovered from COVID-19.
Colorized scanning electron micrograph of a cell (blue) heavily infected with SARS-CoV-2 virus particles (red), isolated from a patient sample.
A new study, which analyzed 40 years of Framingham Heart Study data, found an association between lowered rates of hip fractures and decreases in smoking and heavy drinking.The rates of hip fractures in the United States have been declining over the past few decades. Although some experts attribute this change primarily to improved treatments for bone health, a new National Institutes of Health-supported study suggests other factors. These results indicate that modifiable lifestyle factors, along with treatments, may be beneficial to bone health. The findings appear July 27, 2020 in JAMA Internal Medicine.
The analysis included information from 4,918 men and 5,634 women who participated in the Framingham Study. These individuals were followed for a first hip fracture between Jan. 1, 1970, and Dec. 31, 2010. The rates for hip fractures, which were adjusted for age, dropped by 4.4% each year across the 40-year study period. The decrease was seen in both men and women.
Multi-site trial to test candidate developed by Moderna and NIH
A Phase 3 clinical trial designed to evaluate if an investigational vaccine can prevent symptomatic coronavirus disease 2019 (COVID-19) in adults has begun. The vaccine, known as mRNA-1273, was co-developed by the Cambridge, Massachusetts-based biotechnology company Moderna, Inc., and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The trial, which will be conducted at U.S. clinical research sites, is expected to enroll approximately 30,000 adult volunteers who do not have COVID-19.
“Although face coverings, physical distancing and proper isolation and quarantine of infected individuals and contacts can help us mitigate SARS-CoV-2 spread, we urgently need a safe and effective preventive vaccine to ultimately control this pandemic,” said NIAID Director Anthony S. Fauci, M.D. “Results from early-stage clinical testing indicate the investigational mRNA-1273 vaccine is safe and immunogenic, supporting the initiation of a Phase 3 clinical trial. This scientifically rigorous, randomized, placebo-controlled trial is designed to determine if the vaccine can prevent COVID-19 and for how long such protection may last.”
Moderna is leading the trial as the regulatory sponsor and is providing the investigational vaccine for the trial. The Biomedical Advanced Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response and NIAID are providing funding support for the trial. The vaccine efficacy trial is the first to be implemented under Operation Warp Speed, a multi-agency collaboration led by HHS that aims to accelerate the development, manufacturing and distribution of medical countermeasures for COVID-19.
National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has chosen Michael F. Chiang, M.D., as director of NIH’s National Eye Institute (NEI). A practicing ophthalmologist, Dr. Chiang is currently the Knowles Professor of Ophthalmology & Medical Informatics and Clinical Epidemiology at Oregon Health & Science University (OHSU), Portland, and is associate director of the OHSU Casey Eye Institute. He is expected to begin his new role as the NEI director in late 2020. NEI conducts and supports research and training into blinding eye diseases, visual disorders, mechanisms of visual function, preservation of sight and the special health problems and requirements of the visually impaired.
“Dr. Chiang brings extensive experience as a clinician, researcher and educator to NIH. His work in biomedical informatics and telehealth research are particularly important for the future of vision research,” said Dr. Collins. “I look forward to having him join the NIH leadership team later this year. I also want to recognize Santa J. Tumminia, Ph.D., for her dedicated leadership in serving as the acting director of NEI since October 2019.”
As director, Dr. Chiang will oversee NEI’s annual budget of nearly $824 million, the large majority of which supports vision research through approximately 1,600 research grants and training awards made to scientists at more than 250 medical centers, universities and other institutions across the country and around the world. NEI research leads to sight-saving treatments, reduces visual impairment and blindness and improves the quality of life for people of all ages. The institute also conducts laboratory and patient-oriented research at its own facilities on the NIH campus in Bethesda, Maryland.
IL-17, known for driving inflammation, also puts on the brakes, NIH scientists report
The inflammatory molecule interleukin-17A (IL-17A) triggers immune cells that in turn reduce IL-17A’s pro-inflammatory activity, according to a study by National Eye Institute (NEI) researchers. In models of autoimmune diseases of the eye and brain, blocking IL-17A increased the presence of other inflammatory molecules produced by Th17 cells, immune cells that produce IL-17A and are involved in neuroinflammation. The finding could explain why IL-17-targeted treatments for conditions like the eye disease autoimmune uveitis and multiple sclerosis (MS) have failed. A report on the findings was published in Immunity. NEI is part of the National Institutes of Health.
In autoimmune uveitis, immune cells become abnormally activated and begin to destroy healthy cells, including light-sensing photoreceptors and neurons. A key immune cell involved in this response is the Th17 lymphocyte, which produces several pro-inflammatory molecules known as cytokines. A hallmark of Th17 cells is the ability to produce IL-17A, which attracts immune cells called neutrophils that can damage tissue. Nevertheless, multiple clinical trials of drugs that block IL-17A have failed to help people with autoimmune uveitis or MS.
“IL-17 is the prototypical inflammatory immune molecule blamed for autoimmunity in the neuro-retina and the brain, but there’s been some controversy about the role it plays,” said Rachel Caspi, Ph.D., chief of the Laboratory of Immunology at NEI and senior author of the study. “In our model of autoimmune uveitis, we noticed that without IL-17, the amount of tissue damage unexpectedly stayed the same and we had higher levels of other inflammatory molecules.”
After activation through its T-cell receptor, Th17 cells produce IL-17A, which binds to its own receptor on the Th17 cell. This activates the NFκB pathway. NFκB drives production of IL-24, which in turn suppresses the Th17 cytokine program via SOCS1 and 3.
