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:
Anthony Letai, M.D., Ph.D., was sworn in today as director of the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), by Health and Human Services Secretary Robert F. Kennedy, Jr.
Dr. Letai takes the helm of the world's most prestigious cancer research agency after serving as professor of medicine at Harvard Medical School and medical oncologist at the Dana-Farber Cancer Institute. He possesses decades of experience studying cell death in cancer, developing treatments, and identifying predictive biomarkers.
"Cancer, like other chronic diseases, was long neglected in federal research attention," said Secretary Kennedy. "President Trump reversed that neglect, and Dr. Letai's leadership of NCI will drive American innovation by focusing squarely on the best science to find causes and cures."
With great appreciation for her contributions to NIH, I’d like to announce that Helene M. Langevin, M.D., director of the National Center for Complementary and Integrative Health (NCCIH), is retiring from federal service on November 30, 2025. Since taking the role in 2018, Dr. Langevin has spearheaded the concept of whole person health at NCCIH, focusing on integration across physiological systems and positive health processes, such as resilience and health restoration.
As NCCIH director, Dr. Langevin has led several trans-NIH initiatives that placed whole person health at the forefront of NIH’s emerging unified strategy to address the burden of chronic disease in the U.S. This includes the recent funding of the Whole Person Reference Physiome and Coordination Center, led by NCCIH and co-funded by 20 NIH Institutes, Centers and Offices to create a cross-system network map of healthy physiological function. In collaboration with the CDC National Center for Health Statistics, she steered the development of the Whole Person Health Index, which is currently being deployed in the National Health Interview Survey and the All of Us longitudinal cohort.
I write to share with you the news that Nina Schor, M.D., Ph.D., NIH’s Deputy Director for Intramural Research (DDIR), will be departing from federal service on September 30, 2025. Dr. Schor has served in this role since August 2022, overseeing a massive and complex enterprise of government scientists, program directors, and policy experts as they work to improve the health of the American public. During her tenure, many NIH-wide projects and policies have contributed to advancement towards that important goal.
As DDIR, Dr. Schor leads the NIH Office of Intramural Research (OIR) overseeing faculty recruitment and development, research regulatory affairs, technology transfer, training and education, and research integrity for the NIH Intramural Research Program (IRP), as well as the NIH Stetten Museum. Under Dr. Schor’s leadership, OIR has created and piloted ChIRP, an AI-powered chatbot that gives NIH staff and scientists secure access to the latest large language models (LLMs), as well as launched initiatives to improve data sharing within NIH and enable the creation of custom AI tools for our staff. Furthermore, Dr. Schor has led OIR programs that facilitate NIH-funded collaborations between research groups at NIH and teams of scientists around the country, and she has helped guide NIH toward validation of alternatives to animal models in biomedical research. All these accomplishments have come as she has deftly led OIR’s oversight and support of the thousands of scientific and clinical studies conducted at NIH and its investments in training the next generation of scientists to ensure the United States remains at the forefront of biomedical innovation and discovery.
NIH scientists and collaborators reveal the brain preserves its representation of lost limb in clinical study
In a first-of-its-kind study, researchers found that the brain’s control center for a lost appendage can persist long after surgical amputation, which stands in stark contrast to longstanding theories about the brain’s ability to reorganize itself, also known as plasticity. Scientists from the National Institutes of Health (NIH) and their colleagues examined human brain activity before and after arm amputation and found that the loss of a limb does not prompt a large-scale cerebral overhaul. Published in the journal Nature Neuroscience, this study offers new insight into the mysterious phantom limb syndrome and could help guide the development of neuroprosthetics and pain treatments for people with limb loss.
A team of scientists from NIH and University College London acted on a unique window of opportunity, running MRI scans on three participants in the months prior to a planned amputation (performed for separate medical purposes) and then up to five years after.
“It’s not often you get the chance to conduct a study like this one, so we wanted to be exceedingly thorough,” said co-author Chris Baker, Ph.D., of NIH’s National Institute of Mental Health (NIMH). “We approached our data from a variety of angles and all of our results tell a consistent story.”
During MRI scans, participants moved their hand (pre-amputation) or phantom (post-amputation), as well as their lips (both before and after). Brain maps of the hand (red) and lips (blue) are shown for two pre-amputation scans (pre1, pre2) and multiple post-amputation time points: 3 months, 6 months, and 1.5 years. The maps look the same at each point, demonstrating the stability of the brain's body map after amputation.
Study of human cells and mice may have implications for other lysosomal storage disorders
Scientists at the National Institutes of Health (NIH) successfully reduced the severity of late-onset Tay-Sachs (LOTS) disease in human cell cultures and a mouse model by using a novel gene-editing treatment. LOTS is a rare form of Tay-Sachs disease, with signs and symptoms such as muscle weakness, loss of coordination, muscle spasms, and sometimes loss of mental function beginning in late childhood to adulthood. Similar disorders for which this breakthrough has implications include GM1 gangliosidosis, Sandhoff disease, Niemann-Pick disease, Krabbe disease and Gaucher disease.
LOTS is a genetic disorder caused by a mutation in the HEXA gene that causes a deficiency of an enzyme that is critical to breaking down a fatty substance in the brain, known as GM2 ganglioside. The buildup of this fatty substance damages nerve cells in the brain and spinal cord. The amount of enzyme still being produced by the body affects the severity of the disease and the age of onset. By deploying the correction to the HEXA gene, scientists were able to increase the activity of the enzyme, known as beta-hexosaminidase A, delay symptom onset and significantly extend lifespan in the mouse model.
“With LOTS, a slight correction will go a long way. This editing may only need to increase enzyme activity by about 10 percent to keep symptoms from getting worse, and improve their quality of life,” said paper author Dr. Richard Proia of NIH’s National Institute of Diabetes and Digestive and Kidney Diseases. “We’ve figured out that opening the door to increased enzyme activity is possible, now we have to figure out how to do it in a person.”
NIH case study finds virus drives creation of cancer cells in context of defective T cells
Researchers at the National Institutes of Health (NIH) have shown for the first time that a type of human papillomavirus (HPV) commonly found on the skin can directly cause a form of skin cancer called cutaneous squamous cell carcinoma (cSCC) when certain immune cells malfunction. cSCC is one of the most common cancers in the United States and worldwide. Previously, scientists believed HPV merely facilitated the accumulation of DNA mutations caused by ultraviolet (UV) radiation, usually the primary driver of cSCC. The findings were published today in TheNew England Journal of Medicine.
“This discovery could completely change how we think about the development, and consequently the treatment, of cSCC in people who have a health condition that compromises immune function,” said Andrea Lisco, M.D., Ph.D., of NIH’s National Institute of Allergy and Infectious Diseases (NIAID). “It suggests that there may be more people out there with aggressive forms of cSCC who have an underlying immune defect and could benefit from treatments targeting the immune system.”
There are many different types of HPV, each tending to infect cells in a particular tissue and part of the body. The types of HPV found mostly on the skin — beta-HPV — are considered benign members of the skin microbiome that typically do not integrate into the DNA of skin cells. This contrasts with the alpha types of HPV, known to integrate into the DNA of mucous membrane cells and directly cause cancer of the genitals, anus, head and neck.
The NIH researchers made their discovery in a 34-year-old woman who came to the NIH Clinical Center for evaluation and treatment of recurrent cSCC on her forehead. She had undergone multiple surgeries and a round of immunotherapy to try to remove or kill the tumor, but it repeatedly grew back. Her local doctors thought this was due to an inherited inability to repair DNA damaged by UV radiation plus an impairment in immune cells called T cells. The tumor was one of many progressively worsening HPV-related diseases the woman was experiencing.
Researchers at the National Institutes of Health (NIH) have developed an artificial intelligence (AI) agent powered by a large language model (LLM) that creates more accurate and informative descriptions of biological processes and their functions in gene set analysis than current systems.
The system, called GeneAgent, cross-checks its own initial predictions — also known as claims — for accuracy against information from established, expert-curated databases and returns a verification report detailing its successes and failures. The AI agent can help researchers interpret high-throughput molecular data and identify relevant biological pathways or functional modules, which can lead to a better understanding of how different diseases and conditions affect groups of genes individually and together.
Whole-genome sequencing study found air pollution to cause more cancer-related changes than secondhand smoke
Scientists at the National Institutes of Health (NIH) and their colleagues at the University of California, San Diego, have found that fine-particulate air pollution, which includes pollution from vehicles and industry, was strongly associated with increased genomic changes in lung cancer tumors among people who have never smoked. By assembling the largest-ever whole-genome analysis of lung cancer in individuals who have never smoked, researchers were able to link air pollution exposure to increased cancer-driving and cancer-promoting genetic mutations. This could potentially lead to more prevention strategies for never-smokers.
Researchers analyzed lung tumors from 871 never-smoker patients across 28 geographic locations worldwide as part of the Sherlock-Lung study. They found associations between air pollution exposure and changes in the TP53 gene, and other genetic mutational signatures previously associated with tobacco smoking. They also observed a relationship between air pollution and shorter telomeres, which are sections of DNA found at the end of chromosomes. Telomeres shorten naturally with age and shorter telomeres are related to cells inability to continue to replicate. However, scientists found fine particulate air pollution was linked to premature shortening of telomeres.
Prior genomic studies of lung cancer have focused on tobacco smokers, leaving a significant gap in our understanding of how lung cancer develops in people who have never used tobacco. By beginning to uncover the mechanisms through which tissues acquire cancer-causing or cancer-promoting mutations following environmental exposures, this study helps scientists better understand the primary drivers of lung cancer in this population — which represents up to 25 percent of all lung cancer cases globally.
NIH study could help to guide clinical recommendations for hormone therapy use among women under 55 years old
Scientists at the National Institutes of Health (NIH) have found that two common types of hormone therapy may alter breast cancer risk in women before age 55. Researchers discovered that women treated with unopposed estrogen hormone therapy (E-HT) were less likely to develop the disease than those who did not use hormone therapy. They also found that women treated with estrogen plus progestin hormone therapy (EP-HT) were more likely to develop breast cancer than women who did not use hormone therapy. Together, these results could help to guide clinical recommendations for hormone therapy use among younger women.
The two hormone therapies analyzed in the study are often used to manage symptoms related to menopause or following hysterectomy (removal of uterus) or oophorectomy (removal of one or both ovaries). Unopposed estrogen therapy is recommended only for women who have had a hysterectomy because of its known association with uterine cancer risk.
“Hormone therapy can greatly improve the quality of life for women experiencing severe menopausal symptoms or those who have had surgeries that affect their hormone levels,” said lead author Katie O’Brien, Ph.D., of NIH’s National Institute of Environmental Health Sciences (NIEHS). “Our study provides greater understanding of the risks associated with different types of hormone therapy, which we hope will help patients and their doctors develop more informed treatment plans.”
Findings show this amino acid did not longitudinally decline with age
Scientists at the National Institutes of Health (NIH) have found that levels of circulating taurine, a conditionally essential amino acid involved in multiple important biological functions, is unlikely to serve as a good biomarker for the aging process. In blood samples from humans, monkeys, and mice, scientists found that circulating taurine levels often increased or remained constant with age. Analysis of longitudinal data showed that within individual differences in taurine levels often exceeded age-related changes. Researchers also found that taurine levels were inconsistently associated with health outcomes across age, species, and cohorts, suggesting that declining taurine is not a universal marker of aging. Instead, its impact may depend on individual physiological contexts shaped by genetic, nutritional, and environmental factors. Results are published in Science.
Taurine recently gained popularity as dietary supplement due to recent research that found supplementation with taurine improved multiple age-related traits and extended lifespan in model organisms (worms and mice). However, there is no solid clinical data that shows its supplementation benefits humans.
“A recent research article on taurine led us to evaluate this molecule as a potential biomarker of aging in multiple species,” said Rafael de Cabo, Ph.D., study co-author and chief of the Translational Gerontology Branch at NIH’s National Institute on Aging (NIA).
