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:
Whether you’re shedding pounds with the help of effective new medicines, slimming down after weight loss surgery or cutting calories and adding exercise, there will come a day when the numbers on the scale stop going down, and you hit the dreaded weight loss plateau.
In a recent study, Kevin Hall, a researcher at the National Institutes of Health who specializes in measuring metabolism and weight change, looked at when weight loss typically stops depending on the method people were using todrop pounds. He broke down the plateau into mathematical models using data from high-quality clinical trials of different ways to lose weight to understand why people stop losing when they do. The study published Monday in the journal Obesity.
NIH researchers achieved tumor shrinkage in three of seven patients with colorectal cancers
Early findings from a small clinical trial provide evidence that a new cellular immunotherapy approach may be effective in treating metastatic solid tumors. In the trial, researchers from the National Institutes of Health (NIH) genetically engineered normal white blood cells, known as lymphocytes, from each patient to produce receptors that recognize and attack their specific cancer cells. These initial findings are from people with metastatic colorectal cancer who had already undergone multiple earlier treatments. The personalized immunotherapy shrank tumors in some patients and was able to keep the tumors from regrowing for up to seven months. The findings were published July 11, 2024, in Nature Medicine.
One form of cellular immunotherapy, chimeric antigen receptor (CAR) T-cell therapy, has already been shown to be effective against some blood cancers, and another, called tumor-infiltrating lymphocyte (TIL) therapy, has proven to be effective against metastatic melanoma. However, to date, a cellular therapy that’s effective against any other solid cancers has been elusive, according to Steven A. Rosenberg, M.D., Ph.D., of NCI’s Center for Cancer Research (CCR), who co-led the study with Maria Parkhurst, Ph.D., of CCR’s Surgery Branch.
“The fact that we can take a growing metastatic solid cancer and get it to regress shows that the new cellular immunotherapy approach has promise,” Dr. Rosenberg said. “However, it’s important to understand that these findings are preliminary and that the approach needs to be further refined and tested in more types of solid cancers.”
Cross-sectional CT images showing a metastatic tumor in the left lung of a patient (top image) and no tumor following treatment (bottom image).
The findings in non-human primates could shed light on how our brains develop facial recognition skills
Scientists at the National Institutes of Health (NIH) have uncovered a brain circuit in primates that rapidly detects faces. The findings help not only explain how primates sense and recognize faces, but could also have implications for understanding conditions such as autism, where face detection and recognition are often impaired from early childhood. The newly discovered circuit first engages an evolutionarily ancient part of the brain called the superior colliculus, which can then trigger the eyes and head to turn for a better look. This better view enables different brain areas in the temporal cortex to engage in more complex facial recognition. The study was published in the journal Neuron.
“Quick recognition of faces is a key skill in humans and other primates,” said Richard Krauzlis, Ph.D., of NIH’s National Eye Institute (NEI) and senior author of the study. “This newly discovered circuit explains how we’re able to quickly detect and look at faces, even if they first show up in the peripheral visual field where visual acuity is poor. This circuit could be what spotlights faces to help the brain learn to recognize individuals and understand complex facial expressions, helping us acquire important social interaction skills.”
Researchers Gongchen Yu, Ph.D., Leor Katz, Ph.D., and Richard Krauzlis, Ph.D. have uncovered a brain circuit in primates that rapidly detects faces.
Findings come from an NIH analysis of more than two decades of dietary data from 390,124 U.S. adults
A large analysis of data from nearly 400,000 healthy U.S. adults followed for more than 20 years has found no association between regular multivitamin use and lower risk of death. The study, led by researchers at the National Institutes of Health’s National Cancer Institute, was published June 26, 2024, in JAMA Network Open.
Many adults in the United States take multivitamins with the hope of improving their health. However, the benefits and harms of regular multivitamin use remain unclear. Previous studies of multivitamin use and mortality have yielded mixed results and been limited by short follow-up times.
To more deeply explore the relationship between long-term regular multivitamin use and overall mortality and death from cardiovascular disease and cancer, the researchers analyzed data from three large, geographically diverse prospective studies involving a total of 390,124 U.S. adults who were followed for more than 20 years. The participants included in this analysis were generally healthy, with no history of cancer or other chronic diseases.
Combination therapy developed by NIH researchers demonstrates the power of precision medicine
Researchers at the National Institutes of Health (NIH) have developed a non-chemotherapy treatment regimen that is achieving full remissions for some people with aggressive B-cell lymphoma that has come back or is no longer responding to standard treatments. The five-drug combination targets multiple molecular pathways that diffuse large B-cell lymphoma (DLBCL) tumors use to survive.
In a clinical trial at NIH’s National Cancer Institute, researchers tested the combination of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (called ViPOR) in 50 patients with DLBCL, the most common type of lymphoma. The treatment shrank tumors substantially in 26 of 48 (54%) evaluable patients, with 18 (38%) of those patients’ tumors disappearing entirely, known as a complete response. At two years, 36% of all patients were alive and 34% were free of disease. These benefits were seen mainly in people with two specific subtypes of DLBCL.
The findings were published June 20, 2024, in the New England Journal of Medicine.
“Many of these patients who stopped responding to standard treatments would have otherwise died within a year, and now we have a good proportion who are still alive past two years, and some past four years,” said Christopher J. Melani, M.D., of NCI’s Center for Cancer Research, who co-led the study. “It’s gratifying to see these long-term remissions and potential cures in patients.”
Before treatment with ViPOR, full-body and cross-sectional PET scans of a patient show large lymphoma tumors (circled in the top two panels). Following treatment, the tumors have disappeared (bottom two panels).
The amount of infectious H5N1 influenza viruses in raw milk rapidly declined with heat treatment in laboratory research
The amount of infectious H5N1 influenza viruses in raw milk rapidly declined with heat treatment in laboratory research conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. However, small, detectable amounts of infectious virus remained in raw milk samples with high virus levels when treated at 72 degrees Celsius (161.6 degrees Fahrenheit) for 15 seconds — one of the standard pasteurization methods used by the dairy industry. The authors of the study stress, however, that their findings reflect experimental conditions in a laboratory setting and are not identical to large-scale industrial pasteurization processes for raw milk. The findings were published today in the New England Journal of Medicine
In late March 2024, United States officials reported an outbreak of highly pathogenic avian influenza virus called HPAI H5N1 among dairy cows in Texas. To date, 95 cattle herds across 12 states have been affected, with three human infections detected in farm workers with conjunctivitis. Although the virus so far has shown no genetic evidence of acquiring the ability to spread from person to person, public health officials are closely monitoring the dairy cow situation as part of overarching pandemic preparedness efforts.
Given the limited data on the susceptibility of avian influenza viruses to pasteurization methods used by the dairy industry, scientists at NIAID’s Rocky Mountain Laboratories sought to quantify the stability of H5N1 virus in raw milk when tested at different time intervals at 63℃ (145.4 degrees Fahrenheit) and 72℃, the temperatures most common in commercial dairy pasteurization processes. The scientists isolated HPAI H5N1 from the lungs of a dead mountain lion in Montana. Then they mixed these viral isolates with raw, unpasteurized cow milk samples and heat-treated the milk at 63℃ and 72℃ for different periods of time. The samples were then cell-cultured and tested to determine if live virus remained and if so, how much.
Fresh natural milk on a farm. Given the 2024 multistate outbreak of H5N1 influenza among U.S. dairy cows, federal authorities recommend against drinking unpasteurized (raw) milk.
A genomic analysis co-led by NIH suggests that the DNA a woman is born with may influence how her cells respond to chromosomal abnormalities acquired with aging
Researchers have identified inherited genetic variants that may predict the loss of one copy of a woman’s two X chromosomes as she ages, a phenomenon known as mosaic loss of chromosome X, or mLOX. These genetic variants may play a role in promoting abnormal blood cells (that have only a single copy of chromosome X) to multiply, which may lead to several health conditions, including cancer. The study, co-led by researchers at the National Institutes of Health’s (NIH) National Cancer Institute, was published June 12, 2024, in Nature.
To better understand the causes and effects of mLOX, researchers analyzed circulating white blood cells of nearly 900,000 women across eight biobanks, of whom 12% had the condition. The researchers identified 56 common genetic variants — located near genes associated with autoimmune diseases and cancer susceptibility — that influenced whether mLOX developed. In addition, rare variants in a gene known as FBXO10 were associated with a doubling in the risk of mLOX.
In women with mLOX, the investigators also identified a set of inherited genetic variants on the X chromosome that were more frequently observed on the retained X chromosome than on the one that was lost. These variants could one day be used to predict which copy of the X chromosome is retained when mLOX occurs. This is important because the copy of the X chromosome with these variants may have a growth advantage that could elevate the woman’s risk for blood cancer.
As some women age, their white blood cells can lose a copy of chromosome X. A new study sheds light on the potential causes and consequences of this phenomenon.
In a proof-of-concept study, researchers at the National Institutes of Health (NIH) have developed an artificial intelligence (AI) tool that uses routine clinical data, such as that from a simple blood test, to predict whether someone’s cancer will respond to immune checkpoint inhibitors, a type of immunotherapy drug that helps immune cells kill cancer cells. The machine-learning model may help doctors determine if immunotherapy drugs are effective for treating a patient’s cancer. The study, published June 3, 2024, in Nature Cancer, was led by researchers at the National Cancer Institute’s (NCI) Center for Cancer Research and Memorial Sloan Kettering Cancer Center in New York. NCI is part of the National Institutes of Health.
Currently, two predictive biomarkers are approved by the Food and Drug Administration for use in identifying patients who may be candidates for treatment with immune checkpoint inhibitors. The first is tumor mutational burden, which is the number of mutations in the DNA of cancer cells. The second is PD-L1, a tumor cell protein that limits the immune response and is a target of some immune checkpoint inhibitors. However, these biomarkers do not always accurately predict response to immune checkpoint inhibitors. Recent machine-leaning models that use molecular sequencing data have shown value in predicting response, but this kind of data is expensive to obtain and not routinely collected.
The new study details a different kind of machine-learning model that makes predictions based on five clinical features that are routinely collected from patients: a patient’s age, cancer type, history of systemic therapy, blood albumin level, and blood neutrophil-to-lymphocyte ratio, a marker of inflammation. The model also considers tumor mutational burden, assessed through sequencing panels. The model was constructed and evaluated using data from multiple independent data sets that included 2,881 patients treated with immune checkpoint inhibitors across 18 solid tumor types.
NIH researchers find new pathways towards treatment for autoimmune polyendocrine syndrome type 1
A drug approved to treat certain autoimmune diseases and cancers successfully alleviated symptoms of a rare genetic syndrome called autoimmune polyendocrine syndrome type 1 (APS-1). Researchers identified the treatment based on their discovery that the syndrome is linked to elevated levels of interferon-gamma (IFN-gamma), a protein involved in immune system responses, providing new insights into the role of IFN-gamma in autoimmunity. The study, led by researchers at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, was published today in the New England Journal of Medicine.
In a three-stage study, conducted in mice and people, the researchers examined how APS-1 causes autoimmune disease. The syndrome is marked by dysfunction of multiple organs, usually beginning in childhood, and is fatal in more than 30% of cases. This inherited syndrome is caused by a deficiency in a gene that keeps the immune system’s T cells from attacking cells of the body, leading to autoimmunity; chronic yeast infections in the skin, nails, and mucous membranes; and insufficient production of hormones from endocrine organs, such as the adrenal glands. Symptoms include stomach irritation, liver inflammation, lung irritation, hair loss, loss of skin coloring, tissue damage, and organ failure.
In the first stage of this study, researchers led by scientists in NIAID’s Laboratory of Clinical Immunology and Microbiology examined the natural history of APS-1 in 110 adults and children. Blood and tissues were analyzed to compare gene and protein expression in people with and without APS-1. They found elevated IFN-gamma responses in the blood and tissues of people with APS-1, indicating that IFN-gamma may play an important role in the disease and providing a pathway to target for treatment.
Complete X and Y chromosome sequences from six primate species reveal species diversity and insights into evolution
A team of researchers funded by the National Institutes of Health have generated the first complete chromosome sequences from non-human primates. Published in Nature, these sequences uncover remarkable variation between the Y chromosomes of different species, showing rapid evolution, in addition to revealing previously unstudied regions of great ape genomes. Since these primate species are the closest living relatives to humans, the new sequences can provide insights into human evolution.
The researchers focused on the X and Y chromosomes, which play roles in sexual development and fertility, among many other biological functions. They sequenced chromosomes from five great ape species, chimpanzee, bonobo, gorilla and Bornean and Sumatran orangutans, as well as one other primate species that is more distantly related to humans, the siamang gibbon.
“These chromosome sequences add a significant amount of new information,” said Brandon Pickett, Ph.D., a postdoctoral fellow at the National Human Genome Research Institute (NHGRI), part of NIH, and an author of the study. “Only the chimpanzee genome sequence was fairly complete before this, but even that still had large gaps, especially in regions of repetitive DNA.”
Researchers compared the sequences of the ape chromosomes to the human X and Y chromosomes to understand their evolutionary histories.
AAAS is the world’s largest general scientific society and publisher of the Science family of journals. Newly elected fellows are recognized for scientific and socially notable achievements spanning their careers. Election is one of the most distinguished honors in the scientific community.
AAAS fellows have been recognized for their achievements across disciplines —from research, teaching and technology, to administration in academia, industry and government, to excellence in communicating and interpreting science to the public.
AAAS first launched this lifetime recognition in 1874. Individuals are elected annually by the AAAS council. New fellows are recognized at a ceremonial forum during the AAAS annual meeting, where they are presented with a certificate and blue and gold rosette.
Clockwise from top-left: Dr. Jürgen Wess, Dr. Stephen Chanock, Dr. Erin Lavik, Dr. Julie Segre, Dr. Daniel Reich, and Dr. Gisela Storz
