Selected Grantee Publications
- 729 results found
Glucuronidation Metabolomic Fingerprinting to Map Host–Microbe Metabolism
Boyle et al., Nature Communications. 2026.
https://pubmed.ncbi.nlm.nih.gov/42161945
Glucuronidation is a crucial detoxification pathway for many substances—including hormones, dietary chemicals, medications, and carcinogens—that occurs in the liver, intestines, and kidneys. Glucuronidation operates in balance with a gut microbial enzyme known as β-glucuronidase (GUS). Overactive GUS is connected to such diseases as obesity, inflammatory bowel disease, and colon cancer. In this study, researchers established a measurable, scalable framework for mapping host–microbe interactions that influence the glucuronidome—the collection of metabolites created from glucuronidation. Using public datasets, 4- to 13-week-old male mice, and longitudinal samples from 1- to 12-month-old human infants (sex not stated), results showed that microbial colonization and GUS activity hinder the glucuronidome in the colon but expand urinary glucuronidome variety. These data are available as a resource for future glucuronidome work, and these findings may help advance drug metabolism, diet–microbe interactions, and biomarker discovery research. Supported by ORIP (S10OD021750), NIAID, NIDDK, NIEHS, and NIGMS.
A Forward Genetic Screen Identifies Sirtuin1 as a Driver of Neuroendocrine Prostate Cancer
Nunes de Almeida et al., The Journal of Experimental Medicine. 2026.
https://pubmed.ncbi.nlm.nih.gov/42207152
Neuroendocrine prostate cancer (NEPC) is an aggressive, often lethal version of prostate cancer, but the underlying drivers of NEPC remain unknown. This study featured an integrated systems biology approach that combined three types of analyses—phenotypic (physical traits), transcriptomic (all RNA molecules), and genomic (complete set of DNA)—using human prostate cancer cells, mouse NEPC organoids, and a 2- to 3-month-old male mouse model for NEPC with network-based computational algorithms from two retrospective patient cohorts (n=315 total). Results identified the gene sirtuin 1 (Sirt1) as a driver of NEPC. NEPC tumors showed higher SIRT1 protein activity in patient samples and increased Sirt1 transcript levels in mice compared with non-NEPC tumors. Functional validation—by silencing Sirt1—in cell and organoid cultures confirmed that sirtuin 1 promotes NEPC. Blocking SIRT1 with the drug selisistat also hindered in vitro NEPC tumor growth. These findings highlight that the integrated experimental and computational framework successfully uncovered a new, clinically relevant driver of NEPC. Supported by ORIP (S10OD012351, S10OD021764, S10OD032433), NCATS, NCI, and NIDDK.
Association of MRI-Visible Perivascular Spaces with Longitudinal Cognitive Decline over a Decade
Kohno et al., Neurology. 2026.
https://pubmed.ncbi.nlm.nih.gov/42030516
Small vessel disease (SVD) in the brain is a common contributor to cognitive decline and dementia. Magnetic resonance imaging (MRI) allows for noninvasive tracking of SVD markers in people. Perivascular spaces (PVS) are fluid-filled gaps around vessels that help clear waste from the brain. Researchers followed 750 dementia-free 50- to 92-year-old male and female patients for 11 years to determine whether MRI-visible PVS predicts cognitive decline. Using MRI, machine-learning tools, and cognitive tests, results showed that higher baseline levels of PVS in the basal ganglia (a group of nerve cells located deep within the brain) were significantly correlated with worse cognitive outcomes. MRI scans showed impaired drainage and a buildup of cell waste in the brain. Basal ganglia PVS also predicted worse executive function (processes that control other bodily functions) and visuospatial skills (viewing and understanding the surrounding environment). These findings highlight basal ganglia PVS as a key contributor and possible biomarker for cognitive decline. Supported by ORIP (S10OD021771, S10OD023680), NCATS, NIA, and NICHD.
From Chatbots to Co-scientists: The Impact of Knowledge-Generating AI (AI 4.0) on Healthcare and Research
Liu and Peltz et al., Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2026.
https://pubmed.ncbi.nlm.nih.gov/42411463
Artificial intelligence (AI) 4.0 is a knowledge-generating technology that has advanced reasoning and agentic capabilities—meaning that it can create and complete tasks independently with limited human supervision. In this review article, the authors discuss how AI 4.0 could transform health care by becoming an active partner in biomedical discoveries rather than a tool that only summarizes existing information for researchers. The review article provides an overview of how AI has progressed from previous designs into AI 4.0. The review also highlights a key bottleneck—updating traditional labs to responsibly incorporate AI technology—and opportunities, such as generating testable scientific hypotheses, accelerating drug repurposing, and supporting genetic diagnoses. Supported by ORIP (R24OD035408) and NIDCD.
Monitoring Fetal Somatic Cell Genome Editing In Vivo with Total-Body Positron Emission Tomography: Studies in Rhesus Macaques (Macaca mulatta)
Tarantal et al., Human Gene Therapy. 2026.
https://pubmed.ncbi.nlm.nih.gov/41981831
Gene-editing tools—such as somatic cell genome editing—must be validated to ensure that in utero (in the womb) therapies for inherited disorders are safe and effective. Using 6- to 11‑year-old pregnant nonhuman primates, researchers tested a noninvasive imaging technique to identify edited cells in utero and track potential adverse effects in developing fetuses. First, the researchers delivered a gene-editing tool to fetal livers. Then, total-body positron emission tomography (PET) scans were completed to detect the location and signal persistence of edited cells. Results showed proper insertion in the target gene and sustained editing within the fetal liver. No adverse effects were observed. This study highlights the potential use of the total-body PET imaging technique as a safety monitoring tool, helping future fetal gene-editing therapies be safely and precisely examined. Supported by ORIP (P51OD011107, U42OD027094, S10OD016261, S10OD028713) and NIBIB.
AI in Variant Analysis: Fast Track to Genetic Diagnoses
Wilk et al., Human Genetics. 2026.
https://pubmed.ncbi.nlm.nih.gov/42362888
Although genomic sequencing (a technique to identify the complete set of DNA in an organism) is now more affordable and accessible, understanding the clinical significance of the resulting complex data remains a challenge. In this review article, the authors discuss the use of artificial intelligence (AI) as a clinical decision-support tool to identify disease-causing gene variations from genomic sequencing data, thereby reducing the diagnostic journey for patients with rare genetic diseases. AI tools could be added into diagnostic workflows to help clinicians identify patients who need testing, interpret genetic test results, and prioritize the most important gene variants for care. The review also outlines potential challenges for combining AI tools with clinical care—including patient privacy, quality of and potential bias in training data, and validation. Using AI as a clinical decision-support tool could help reduce unnecessary clinical visits, medical costs, patient anxiety, and missed treatment opportunities, highlighting its potential for enabling efficient, personalized medical interventions. Supported by ORIP (U54OD030167) and NIDDK.
Patient-Specific Midbrain Organoids with CRISPR Correction Recapitulate Neuronopathic Gaucher Disease Phenotypes and Enable Evaluation of Novel Therapies
Lin et al., eLife. 2026.
https://pubmed.ncbi.nlm.nih.gov/42334452
Gaucher disease (GD) is caused by a mutation in the GBA1 gene that causes accumulation of specific molecules, leading to inflammation and neurodegeneration (a decline in the nervous system and brain). Neuronopathic GD (nGD) is a severe form of GD, and preclinical models do not fully mimic the disease. In this study, researchers developed brain-like organoids (3D cell cultures) from nGD patient cells (sex not stated). Results showed that these organoids display key disease features, including reduced enzyme activity levels, buildup of harmful lipids (fat), and disrupted brain cell development. Using a gene editing technique, researchers corrected the GBA1 mutation in the organoids and observed a reduction in these disease characteristics. The researchers also tested three possible treatments: enzyme delivery using nanoparticles, gene therapy, and a drug that reduces fat production. These treatments showed promising results for restoring normal function. These findings highlight the utility of patient-derived nGD organoids for identifying the underlying mechanisms of GD, testing new therapies, and supporting personalized treatment development. Supported by ORIP (R21OD033660), NCATS, NHGRI, NICHD, and NINDS.
Targeted Near-Infrared Photoacoustic Probes for Dual-Channel Cartilage and Bone Imaging
Amer et al., Angewandte Chemie (International ed. in English). 2026.
https://pubmed.ncbi.nlm.nih.gov/42313677
The ability to image cartilage and bone at the same time remains an unmet need for musculoskeletal research and image-guided surgery. In this study, researchers developed near-infrared (NIR) photoacoustic probes (an imaging technique that uses light and ultrasound to detect sound waves and form images)—Cart‑670 and Osteo-750—that allow simultaneous molecular imaging of cartilage and bone during a single imaging session. To create these probes, the researchers screened NIR-absorbing, non-fluorescent dyes, and they identified QSY21 as the ideal dye. QSY21 was bound to a cartilage-targeting molecule to create the Cart-670 probe. The Osteo‑750 probe was made by combining a fluorophore with a molecule that targets bone. In an ex vivo (outside the whole organism) chicken model, results showed that these probes had low detection limits and were highly selective to the tissues of interest. These findings support the use of these probes to image cartilage–bone junctures. Supported by ORIP (S10OD032268).
A Universal 6iL/E4 Culture System for Deriving and Maintaining Embryonic Stem Cells Across Mammalian Species
Wang et al., Cell Research. 2026.
https://pubmed.ncbi.nlm.nih.gov/42443522
Embryonic stem cells (ESCs) can become many different types of cells during embryonic development. Obtaining ESCs from embryos remains a challenge for biomedical research. In this study, researchers developed a serum-free culture system—6iL/E4—that allows ESCs to be acquired from different animal models. This culture system also allows ESCs to self-renew (divide into new cells forever). Results showed successful use of this system for mouse, rat, rabbit, and cow embryos. The culture system required an extra drug to successfully obtain rabbit ESCs. Several cell-signaling pathways—GSK3α, WNT, STAT3, PDGFR, and MEK/ERK—were shared across the different species and allowed ESCs to remain in an early, flexible cell state. The culture system also was able to maintain human pluripotent stem cells (cells that develop into many different types of cells). This system may serve as a universal platform to support stem cell research, disease modeling studies, and biotechnology development. Supported by ORIP (R24OD039745, R41OD023245), NHLBI, NICHD, NIDDK, and NIGMS.
MYC Is Functionally Required in Both Normal and Neoplastic Meibomian Glands
Boyack et al., The American Journal of Pathology. 2026.
https://pubmed.ncbi.nlm.nih.gov/42392260
Ocular adnexal sebaceous carcinoma (SebCA) is an aggressive and rare cancer that starts in the meibomian gland (MG) (oil gland in the eyelid). In this study, researchers examined whether MYC, a gene that helps control cell growth, is important for normal and cancer cells of the MG. Using 42- to 70-day-old mice (both sexes used), results showed that blocking MYC decreased MG cell size, slowed MG cell growth, increased MG apoptosis (cell death), and altered oil droplet formation. Inhibiting MYC in SebCA cells reduced cell proliferation (the ability to make new cells), diminished viability (the number of live cells), and decreased the formation of cell colonies. These findings highlight the role of MYC in supporting gland health and contributing to SebCA development. Supported by ORIP (K01OD034451, T35OD033655).