Selected Grantee Publications
- 666 results found
The NeuroBioBank Whole-Genome Catalogue of Human Brain Donors with Central Nervous System Disorders
Hupalo, Brain. 2026.
https://pubmed.ncbi.nlm.nih.gov/41697960
Biobanking facilities are vital for disease studies. The NIH NeuroBioBank has created a thorough, whole-genome catalogue of 9,663 brain tissue donors with central nervous system (CNS) disorders. This resource includes array-based genotyping (a process to identify genetic variations) and whole-genome sequencing (defining the entire DNA sequence) across 148 CNS diseases. Brain tissue, collected from donors averaging age 60 and largely of European descent, was collected from six repositories with detailed clinical and neuropathological characteristics. The dataset contains 171 million unique variants and more than 1 million non-silent variants (gene mutations that alter the transcribed protein), all annotated for functional impact. Available through the NIMH Data Archive and NeuroBioBank Portal, this resource aids genetic risk and disease mechanism studies. Proof-of-concept analyses successfully replicated known gene associations for Huntington’s disease and Alzheimer’s disease. Supported by ORIP (C06OD030170), NIDA, and NIA.
Genomic Insights into Inflammatory Bowel Disease in United States Hispanic Participants: An Ancestry-Focused Study
Beecham, Gastroenterology. 2026.
https://pubmed.ncbi.nlm.nih.gov/41661118
Gut diseases—including inflammatory bowel disease (IBD) and Crohn’s disease (CD)—are chronic illnesses triggered by immune dysfunction, and they are a major health care burden. Increased rates of IBD, CD, and ulcerative colitis have been seen in minority populations, notably Hispanic people. In this study, researchers completed an ancestry-informed genome-wide association analysis of approximately 7,300 Hispanic people (both sexes used) from the United States. Results found new IBD risk alleles (different versions of the same gene) that were specific to African and Amerindian populations. Previously known IBD risk loci (the physical location of genes on a chromosome) were identified to be specific to European populations. Clinical phenotypes showed important ancestral heterogeneity (distinct differences). African ancestry was associated with colonic, penetrating, or perianal CD, and Amerindian ancestry was linked to colonic disease. New genome-wide links were discovered in 14 loci for African or Amerindian alleles, with several showing replication and the ability to transfer across populations. These findings highlight the biological foundation of IBD through genetic ancestry analysis and carry significant drug treatment implications for precision medicine approaches. Supported by ORIP (C06OD030170), NHGRI, NHLBI, and NIDDK.
Tumor-Infiltrating Bacteria Disrupt Cancer Epithelial Cell Interactions and Induce Cell-Cycle Arrest
Galeano Niño, Cancer Cell. 2026.
https://pubmed.ncbi.nlm.nih.gov/41106380
Tumor-infiltrating bacteria have been linked to cancer recurrence and resistance to treatment. For example, Fusobacterium nucleatum in colorectal cancer correlates with poor prognosis. However, it is not well known how bacteria become a key component of the tumor microenvironment and influence tumor characteristics. Using cell cultures, samples from colorectal or oral cavity squamous cell carcinoma patients, and mouse models (sex not specified), researchers showed that F. nucleatum disturbs epithelial contacts among cancer cells to cause cell cycle arrest and transcriptional (making a copy of RNA from DNA) dormancy, which promotes chemotherapy resistance and remodeling of the tumor microenvironment. Bacteria-enriched regions of tumors showed decreased expression of genes that created a phenotype (physical characteristics) that evaded immune detection. This study identifies microbial–tumor interactions that could be targeted in novel treatments to reduce poor cancer outcomes. Supported by ORIP (C06OD032074), NCI, NIDCR, and NIMHD.
Extracellular Matrix Mediates Circulating Tumor Cell Clustering in Triple-Negative Breast Cancer Metastasis
Bobkov, Nature Communications. 2026.
https://pubmed.ncbi.nlm.nih.gov/41651843
The leading cause of cancer-related death is the spreading of tumor cells (metastasis) to secondary sites of the body. In aggressive triple-negative breast cancer (TNBC), clustered circulating tumor cells (CTCs) exhibit greater metastatic potential than single CTCs, but the underlying mechanism for this clustered CTC characteristic in TNBC cells—which lack typical adherens junction proteins for cell–cell interactions—remains unknown. Using TNBC blood samples, cell cultures, and 6- to 8-week-old female mice, researchers identified an extracellular component—hyaluronan—that mediates adherens junction–independent CTC clustering through the cell receptor CD44. Hyaluronan first helps cells make initial contact by triggering arm-like projections on the cell surface, which then expand into broader cell-to-cell connections held in place by structural anchors called desmosomes. CTC-derived hyaluronan also acts as a docking platform for other circulating cells, including immune cells, to form a cluster of different cell types. The hyaluronan–CD44 interaction allows the clustered CTCs to survive the hemodynamic shear stress of blood flowing through blood vessels, which enhances metastasis. This study identifies an underlying mechanism used by TNBC cells to spread to secondary sites, and it could be a target for new TNBC treatments. Supported by ORIP (S10OD016167, S10OD020151, S10OD030414), NCI, NICHD, NIDDK, NIEHS, and NIGMS.
Lamina Propria Collagen Architecture in Interstitial Cystitis/Bladder Pain Syndrome
Ruetten, Journal of Histochemistry and Cytochemistry. 2026.
https://pubmed.ncbi.nlm.nih.gov/41546563
A chronic pelvic pain disorder known as interstitial cystitis/bladder pain syndrome (IC/BPS) affects about 5% of people in the United States. Patients with IC/BPS experience increased health care needs and costs. The cause of IC/BPS remains uncertain, and patients present with a broad range of symptoms. These factors hinder effective treatment of IC/BPS. In this study, researchers obtained bladder biopsies from 44 female patients and examined collagen characteristics in phenotypically (physical characteristics) distinct IC/BPS subgroups. Hunner lesions (HL) patients had additional acute and chronic inflammation, more narrow collagen fibers, and increased collagen around the bladder compared with non-HL IC/BPS patients and control patients. Regardless of subgroup, all IC/BPS patients showed lower collagen fiber density than control patients. The results highlight unique collagen characteristics across subgroups. Supported by ORIP (T32OD010957), NCI, and NIDDK.
Fatty Acid Synthase as a Potential Metabolic Vulnerability in Ocular Adnexal Sebaceous Carcinoma
Berlied, Cancers (Basel). 2026.
https://pubmed.ncbi.nlm.nih.gov/41595267
Ocular adnexal sebaceous carcinoma (SebCA) is an aggressive cancer of the eyelid, and no targeted treatments are available. MYC is a protein found to be increased in SebCA. MYC helps regulate lipid metabolism (a process that creates and degrades fats) and promote tumor growth. Other cancer models have shown promise with targeting lipid metabolism as a possible treatment. Using human SebCA cell cultures and a mouse model for SebCA (both sexes used), the researchers showed that blocking FASN—a protein vital for creating the building blocks of lipids—reduced the number of live cancer cells and prevented proliferation (increase in cell numbers). These findings highlight that metabolic weaknesses in cancers may serve as useful targets for SebCA. Supported by ORIP (K01OD034451, T35OD033655).
Sulfur-Containing Class of Broad-Spectrum Antivirals Improves Influenza Virus Vaccine Development
Buchholz, Nature Communications. 2026.
https://pubmed.ncbi.nlm.nih.gov/41495036
Enveloped viruses are a type of virus that have an outer lipid (fat) membrane derived from the host cell during viral replication. Enveloped viruses are most likely to trigger pandemics and are a severe threat for zoonotic diseases (infectious illnesses that can spread from animals to humans). The ability to quickly make effective vaccines for viruses that are a threat to public health is important. Researchers found a class of small-molecule antiviral compounds that broadly blocks enveloped viruses by preventing membrane fusion and viral entry into a host cell. The researchers developed a flu virus vaccine using one of these compounds. Using an 8‑week-old mouse model (both sexes used), the researchers observed a stronger neutralizing antibody (a protein that blocks microbes from infecting host cells) response when given the vaccine. When the mice were exposed to influenza virus, morbidity and mortality were greatly reduced compared with control mice that received a mock vaccine. These findings highlight a promising class of antiviral compounds that could be used to create potent vaccines against enveloped viruses. Supported by ORIP (T32OD011000), NHLBI, NIAID, NIBIB, and NIGMS.
Monitoring Biological Effects of Somatic Cell Genome Editing
Freedman et al., Nature Reviews Genetics. 2026.
https://pubmed.ncbi.nlm.nih.gov/41530266
CRISPR-based genome editing is an innovative technique for treating a variety of diseases. This therapy is entering the clinic, and preclinical-to-clinical tools are needed to ensure the therapy is safe and effective. Researchers affiliated with the Somatic Cell Genome Editing (SCGE) Consortium provided a review of these efforts. The review outlines key technologies—including microphysiological systems and noninvasive in vivo (within an organism) imaging—to examine the on-target and off-target biological effects of genome editing in different organ systems and disease settings. Microphysiological systems, such as organoids and organ-on-a-chip, are useful for modeling physical characteristics of human physiology and disease. Examples of these models for a broad range of diseases and their use for gene editing applications were discussed. Challenges related to these methods were noted. The review also explained how microphysiological systems complement traditional preclinical models—including mouse models—because of species differences when compared with humans. The researchers highlighted lessons learned from the NIH-funded SCGE Biological Effects Initiative and outlined a proposed framework for the integration of these technologies into the development of genome-editing therapies. Supported by ORIP (P51OD011107, S10OD016261, S10OD018102, S10OD028713, and U42OD027094), NCATS, NHGRI, NHLBI, NIA, NIAID, NIBIB, NIDDK, NIEHS, NIGMS, and NINDS.
Therapeutic Remodeling of the Ceramide Backbone Prevents Kidney Injury
Nicholson et al., Cell Metabolism. 2026.
https://pubmed.ncbi.nlm.nih.gov/41232539
Acute kidney injury (AKI) can be caused by a broad range of conditions, including drug toxicity, sepsis, preexisting kidney disorders, and heart failure. AKI increases a person’s chance for chronic kidney disease, morbidity, and mortality, but an effective therapy for AKI is not currently available. Proximal tubules (PTs) within the kidney secrete nonfiltered substances while reabsorbing filtered molecules. Abnormal lipid metabolism and lipid imbalances are linked to AKI, but the underlying mechanisms remain unknown. Using previously published data, urine samples from patients, and 8- to 11-week-old male mouse models, researchers showed that AKI triggers the production of toxic ceramides in PTs and that urine ceramide levels correlate with disease severity. Ceramides disrupt mitochondrial structure and function by altering critical protein complexes, and damage requires a specific molecular feature of ceramides created by the DES1 enzyme. Genetic deletion of DES1 protected mice from kidney injury following bilateral ischemia reperfusion. A novel DES1 inhibitor provided a protective effect, offering a promising therapeutic strategy. This work reveals ceramide remodeling as a promising target for treating AKI. Supported by ORIP (S10OD016232, S10OD018210, and S10OD021505), NCI, NHLBI, NIA, NIDDK, and NIGMS.
A Method for Discovery of Transcription Factors Controlling Brucella sRNAs
Caudill et al., Microbiology Spectrum. 2026.
https://pubmed.ncbi.nlm.nih.gov/41230967
Regulatory small RNAs (sRNAs) control translation of many proteins that are linked to virulence (ability of the bacteria to cause disease) in pathogenic bacteria—including Brucella species—which allows for them to regulate internal processes to conserve and respond to environmental changes. For Brucella species, 40 sRNAs have been identified, but the transcription factors and conditions that control sRNAs remain unknown. In this study, researchers developed a method, by using publicly available datasets of Brucella species, to discover the transcription factors and conditions that control sRNAs. A list of predicted regulatory relationships was created, and the researchers validated several predicted regulatory relationships using Northern blots. A female mouse model also was used to identify transcription factors that may be involved in host infection by B. abortus. This method can be applied to other bacteria studies to help understand pathogenesis and the virulence factors mediated by sRNAs. Supported by ORIP (T32OD028239) and NIAID.