In the News

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:

IRP researchers unlock pattern of gene activity for ADHD

New study uses postmortem brain tissues to understand genomic differences in individuals with attention deficit hyperactivity disorder

Researchers at the National Institutes of Health have successfully identified differences in gene activity in the brains of people with attention deficit hyperactivity disorder (ADHD). The study, led by scientists at the National Human Genome Research Institute (NHGRI), part of NIH, found that individuals diagnosed with ADHD had differences in genes that code for known chemicals that brain cells use to communicate. The results of the findings, published in Molecular Psychiatry, show how genomic differences might contribute to symptoms.

To date, this is the first study to use postmortem human brain tissue to investigate ADHD. Other approaches to studying mental health conditions include non-invasively scanning the brain, which allows researchers to examine the structure and activation of brain areas. However, these studies lack information at the level of genes and how they might influence cell function and give rise to symptoms.

The researchers used a genomic technique called RNA sequencing to probe how specific genes are turned on or off, also known as gene expression They studied two connected brain regions associated with ADHD: the caudate and the frontal cortex. These regions are known to be critical in controlling a person’s attention. Previous research found differences in the structure and activity of these brain regions in individuals with ADHD.

Experimental cancer vaccine shows promise in animal studies

NIH researchers find IV administration improves tumor-fighting action

An experimental therapeutic cancer vaccine induced two distinct and desirable immune system responses that led to significant tumor regression in mice, report investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. 

The researchers found that intravenous (IV) administration of the vaccine boosted the number of cytotoxic T cells capable of infiltrating and attacking tumor cells and engaged the innate immune system by inducing type I interferon. The innate immune response modified the tumor microenvironment, counteracting suppressive forces that otherwise would tamp down T-cell action. Modification of the tumor microenvironment was not seen in mice that received the vaccine via needle injection into the skin (subcutaneous administration).

Dubbed “vax-innate” by the scientific team, the approach achieves an important goal in the quest for more effective immunotherapeutic vaccines for cancer. The study demonstrates that IV vaccine delivery enables and enhances T-cell immunity by overcoming tumor-induced immunosuppressive activity. The researchers say the candidate vaccine might also be given intravenously to people who have already received tumor-specific T cells as a therapy. It also could improve tumor control by increasing the number of T cells and altering the tumor microenvironment to make them function better, the researchers note.

NIH names Dr. Joni L. Rutter director of the National Center for Advancing Translational Sciences

Lawrence A. Tabak, D.D.S., Ph.D., who is performing the duties of the National Institutes of Health director, has selected Joni L. Rutter, Ph.D., as director of NIH’s National Center for Advancing Translational Sciences (NCATS). Dr. Rutter has served as NCATS acting director since April 2021. She officially began her role as NCATS director on Nov. 6, 2022.

Dr. Rutter will oversee a diverse portfolio of research activities focused on improving the translational process of turning scientific discoveries into health interventions. The portfolio includes the Clinical and Translational Science Awards (CTSA) Program, which is one of NIH’s largest supported programs and has played an important role in the agency’s COVID-19 response. In addition, she will direct innovative research programs to advance diagnoses and treatments, including gene therapies, for some of the more than 10,000 known rare diseases. She also will lead labs at NIH that drive team science with the private sector to create and test innovative methods for improving the drug development process.

“Dr. Rutter took the helm at NCATS during the most critical public health challenge of our time,” said Dr. Tabak. “Throughout her scientific career and leadership roles at NIH, she has been at the forefront of many exciting and innovative initiatives, and I have great confidence that she will lead NCATS in accelerating the development paths for turning discoveries into treatments.” 

Dr. Joni L. Rutter

NCATS Director Joni L. Rutter, Ph.D.

New 3D model shows how cadmium exposure may affect heart development

NIH researchers develop new tools to demonstrate how environmental agents can lead to diseases

Researchers have developed a three-dimensional model that shows how exposure to cadmium might lead to congenital heart disease. Affecting nearly 40,000 newborns a year, congenital heart disease is the most common type of birth defect in the United States. The model was created by scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.

Cadmium is a metal that can be released into the environment through mining and various industrial processes, and it has been found in air, soil, water, and tobacco. The metal can enter the food chain when plants absorb it from soil. Previous studies suggested that maternal exposure to cadmium might be a significant risk factor for congenital heart disease.

Using models derived from human cells and tissues, called in vitro models, researchers designed a 3D organoid model that mimics how the human heart develops. The researchers saw how exposure to low levels of cadmium can block usual formation of cardiomyocytes, which are the major type of cells that form the heart. In doing so, they revealed the biological mechanisms that might explain how cadmium could induce heart abnormalities.

“The models we created are useful for not only studying cadmium, but for studying other chemicals and substances as well,” said study lead Erik Tokar, Ph.D., from the Mechanistic Toxicology Branch of the NIEHS Division of Translational Toxicology (DTT).

2D model showing how the pluripotent stem cells react to human relevant doses of cadmium over 8 days

2D model showing how the pluripotent stem cells react to human relevant doses of cadmium over 8 days. From the control in the first panel, to the last panel, researchers can see how the differentiation to cardiomyocytes is inhibited with different doses of cadmium.

IRP study in mice provides insight into how brain activity is fine-tuned

Research explores how new information is consolidated across the sleep-wake cycle

Using a mouse model, researchers have discovered a new daily rhythm in a type of synapse that dampens brain activity. Known as inhibitory synapses, these neural connections are rebalanced so that we can consolidate new information into long-lasting memories during sleep. The findings, published in PLOS Biology, may help explain how subtle synaptic changes enhance memory in humans. The study was led by researchers at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

“Inhibition is important for every aspect of brain function. But for over two decades, most sleep studies have focused on understanding excitatory synapses,” said Dr. Wei Lu, senior investigator at NINDS. “This is the first study to try to understand how sleep and wakefulness regulate inhibitory synapses.”

In the study, Kunwei Wu, Ph.D., a postdoctoral fellow in Dr. Lu’s lab, examined what happens at inhibitory synapses during sleep and wakefulness in mice. Electrical recordings from neurons in the hippocampus — a brain region important for memory formation — showed a previously unappreciated pattern of activity. During wakefulness, steady 'tonic' inhibitory activity increased, while fast 'phasic' inhibition decreased. They also found much larger activity-dependent enhancement of inhibitory electrical responses in neurons from awake mice suggesting that wakefulness, but not sleep, could strengthen these synapses to a greater degree.

Interneurons (green) in the hippocampus of a mouse

Interneurons (green) in the hippocampus of a mouse

Monoclonal antibody prevents malaria infection in African adults

One dose of an antibody drug safely protected healthy, non-pregnant adults from malaria infection during an intense six-month malaria season in Mali, Africa, a National Institutes of Health clinical trial has found. The antibody was up to 88.2% effective at preventing infection over a 24-week period, demonstrating for the first time that a monoclonal antibody can prevent malaria infection in an endemic region. These findings were published today in The New England Journal of Medicine and presented at the American Society of Tropical Medicine & Hygiene 2022 Annual Meeting in Seattle.

“We need to expand the arsenal of available interventions to prevent malaria infection and accelerate efforts to eliminate the disease,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “These study results suggest that a monoclonal antibody could potentially complement other measures to protect travelers and vulnerable groups such as infants, children, and pregnant women from seasonal malaria and help eliminate malaria from defined geographical areas.”

NIAID sponsored and funded the trial, which was led by Peter D. Crompton, M.D., M.P.H., and Kassoum Kayentao, M.D., M.P.H., Ph.D. Dr. Crompton is chief of the Malaria Infection Biology and Immunity Section in the NIAID Laboratory of Immunogenetics, and Dr. Kayentao is a professor at the University of Sciences, Techniques and Technologies (USTTB) of Bamako, Mali.

diagram showing how an antibody drug called CIS43LS prevents malaria infection by interrupting the lifecycle of the Plasmodium falciparum parasite.

An antibody drug called CIS43LS prevents malaria infection by interrupting the lifecycle of the Plasmodium falciparum parasite. The antibody binds to and neutralizes sporozoites, the stage of the parasite transmitted from mosquitos to humans.

Experimental monoclonal antibodies show promise against Epstein-Barr virus

A panel of investigational monoclonal antibodies (mAbs) targeting different sites of the Epstein-Barr virus (EBV) blocked infection when tested in human cells in a laboratory setting. Moreover, one of the experimental mAbs provided nearly complete protection against EBV infection and lymphoma when tested in mice. The results appear online today in the journal Immunity. Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in collaboration with researchers from Walter Reed Army Institute of Research, led the study.

EBV is one of the most common human viruses. After an EBV infection, the virus becomes dormant in the body but may reactivate in some cases. It is the primary cause of infectious mononucleosis and is associated with certain cancers, including Hodgkin lymphoma, and autoimmune diseases, such as multiple sclerosis. People with weakened immune systems, such as transplant recipients, are more likely than immunocompetent people to develop severe symptoms and complications from EBV infection. There is no licensed vaccine to protect against the virus.

The researchers developed several investigational mAbs targeting two key proteins—gH and gL—found on EBV’s surface. The two proteins are known to facilitate EBV fusion with human cells and cause infection. When tested in the laboratory setting, the investigational mAbs prevented EBV infection of human B cells and epithelial cells, which line the throat at the initial site of EBV infection. Analyzing the structure of the mAbs and their two surface proteins using X-ray crystallography and advanced microscopy, the researchers identified multiple sites of vulnerability on the virus to target. When tested in mice, one of the experimental mAbs, called mAb 769B10, provided almost complete protection against EBV infection when given. The mAb also protected all mice tested from EBV lymphoma.

An electron microscopy image showing three Epstein-Barr virions

An electron microscopy image showing three Epstein-Barr virions

IRP researchers home in on a new cause of Stargardt disease

Study may help lead to gene therapy for rare inherited blinding disease

Using a new stem-cell based model made from skin cells, scientists found the first direct evidence that Stargardt-related ABCA4 gene mutations affect a layer of cells in the eye called the retinal pigment epithelium (RPE). The discovery points to a new understanding of Stargardt disease progression and suggests a therapeutic strategy for the disease, which currently lacks treatment. The study took place at the National Eye Institute (NEI), part of the National Institutes of Health. The findings published online today in Stem Cell Reports.

“This new model will accelerate development of therapies for Stargardt disease,” said NEI Director Michael F. Chiang, M.D. “We lack a therapy for this disease in part because it’s rare. This model theoretically creates an unlimited supply of human cells for study.” Stargardt affects about 1 in every 10,000 people in the U.S.

Stargardt disease causes progressive loss of central and night vision. The vision loss is associated with the toxic build-up of lipid-rich deposits in the RPE, whose main job is to support and nourish the retina’s light sensing photoreceptors. Under normal conditions, the ABCA4 gene makes a protein that prevents this toxic build-up. Prior research showed that Stargardt disease is caused by a variety of mutations in the ABCA4 gene. More than 800 ABCA4 mutations are known to be associated with a broad spectrum of Stargardt disease phenotypes.

A cross section of the stem-cell generated RPE is shown after it has been fed photoreceptor outer segments. Arrows point to lipid deposits (green). This buildup of lipids is toxic to the cell, and similar to that seen in patients with Stargardt disease.

A cross section of the stem-cell generated RPE is shown after it has been fed photoreceptor outer segments. Arrows point to lipid deposits (green). This buildup of lipids is toxic to the cell, and similar to that seen in patients with Stargardt disease.

IRP scientists discover essential step in recharging the eye’s light-sensing retina

Scientists have discovered a mechanism by which an area of a protein shape-shifts to convert vitamin A into a form usable by the eye’s light-sensing photoreceptor cells. A previously uncharacterized area of the protein known as RPE65 spontaneously turns spiral-shaped when it encounters intracellular membranes, or thin structures that surround different parts of a cell.

This shapeshifting enables RPE65 to enter the endoplasmic reticulum — a network of sac-like structures and tubes — where RPE65 performs the crucial task of vitamin A conversion. The scientists say the discovery provides better understanding of RPE65’s function and will inform potential treatments for vision disorders linked to RPE65 gene mutations. Researchers at the National Eye Institute, part of the National Institutes of Health, conducted the research, which published in Life Science Alliance.

Hair straightening chemicals associated with higher uterine cancer risk

Women who used chemical hair straightening products were at higher risk for uterine cancer compared to women who did not report using these products, according to a new study from the National Institutes of Health. The researchers found no associations with uterine cancer for other hair products that the women reported using, including hair dyes, bleach, highlights, or perms.

The study data includes 33,497 U.S. women ages 35-74 participating in the Sister Study, a study led by the National Institute of Environmental Health Sciences (NIEHS), part of NIH, that seeks to identify risk factors for breast cancer and other health conditions. The women were followed for almost 11 years and during that time 378 uterine cancer cases were diagnosed. 

The researchers found that women who reported frequent use of hair straightening products, defined as more than four times in the previous year, were more than twice as likely to go on to develop uterine cancer compared to those who did not use the products.

“We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%,” said Alexandra White, Ph.D., head of the NIEHS Environment and Cancer Epidemiology group and lead author on the new study. “This doubling rate is concerning. However, it is important to put this information into context - uterine cancer is a relatively rare type of cancer.”

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This page was last updated on Wednesday, May 11, 2022