Thursday, August 6, 2020
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.
Lindsey A. Criswell, M.D., M.P.H., D.Sc.
Wednesday, August 5, 2020
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.
Thursday, July 30, 2020
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.
The research team was led by Joshua Zimmerberg, M.D., Ph.D., a senior investigator in the Section on Integrative Biophysics at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study appears in Nature Communications.
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.
Tuesday, July 28, 2020
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.
Monday, July 27, 2020
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.
Timothy Bhattacharyya, M.D., a researcher with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of NIH, led the analysis to determine what may be causing the drop in hip fracture rates. The research team included scientists from NIH’s National Cancer Institute, the Hinda and Arthur Marcus Institute for Aging Research, part of the Hebrew SeniorLife, Beth Israel Deaconess Medical Center, Boston, and Harvard Medical School, Boston.
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.
Monday, July 27, 2020
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.
Friday, July 24, 2020
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.
Dr. Michael F. Chiang
Thursday, July 23, 2020
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.
Monday, July 20, 2020
Gene expression data suggest potential role of sex chromosomes
A scientific analysis of more than 2,000 brain scans found evidence for highly reproducible sex differences in the volume of certain regions in the human brain. This pattern of sex-based differences in brain volume corresponds with patterns of sex-chromosome gene expression observed in postmortem samples from the brain’s cortex, suggesting that sex chromosomes may play a role in the development or maintenance of sex differences in brain anatomy. The study, led by researchers at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, is published in Proceedings of the National Academy of Sciences.
“Developing a clearer understanding of sex differences in human brain organization has great importance for how we think about well-established sex differences in cognition, behavior, and risk for psychiatric illness. We were inspired by new findings on sex differences in animal models and wanted to try to close the gap between these animal data and our models of sex differences in the human brain,” said Armin Raznahan, M.D., Ph.D., study co-author and chief of the NIMH Section on Developmental Neurogenomics.
Researchers have long observed consistent sex-based differences in subcortical brain structures in mice. Some studies have suggested these anatomical differences are largely due to the effects of sex hormones, lending weight to a “gonad-centric” explanation for sex-based differences in brain development. However, more recent mouse studies have revealed consistent sex differences in cortical structures, as well, and gene-expression data suggest that sex chromosomes may play a role in shaping these anatomical sex differences. Although the mouse brain shares many similarities with the human brain, it is not clear whether these key findings in mice also apply to humans.
Tuesday, July 14, 2020
The accomplishment opens a new era in genomics research
Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, have produced the first end-to-end DNA sequence of a human chromosome. The results, published today in Nature, show that generating a precise, base-by-base sequence of a human chromosome is now possible, and will enable researchers to produce a complete sequence of the human genome.
Humans have two sets of chromosomes, one set from each parent. For example, biologically female humans inherit two X chromosomes, one from their mother and one from their father. However, those two X chromosomes are not identical and will contain many differences in their DNA sequences.
In this study, researchers did not sequence the X chromosome from a normal human cell. Instead, they used a special cell type – one that has two identical X chromosomes. Such a cell provides more DNA for sequencing than a male cell, which has only a single copy of an X chromosome. It also avoids sequence differences encountered when analyzing two X chromosomes of a typical female cell.