Programs and Activities Highlights
- Final Site Visit to the University of Illinois Chicago
On July 14, 2025, ORIP staff performed a virtual site visit to two NIH-funded facilities at The University of Illinois Chicago that were supported by grants C06RR016560 and C06RR020087. The Center for Structural Biology building met all objectives, providing state-of-the-art nuclear magnetic resonance spectrometry, electron microscopy, and mass spectrometry cores that now serve more than 225 internal and 130 external users. Expanded instrumentation, increased user demand, and improved environmental sustainability have driven significant growth, including major increases in core revenue, multiple patents, startup companies, and federally supported drug discovery efforts. The Behavioral Neurobiology Center renovation modernized outdated laboratories and created integrated basic and clinical neuroscience research spaces. The facility enabled substantial faculty and trainee recruitment, approximately $60 million in grant funding, and hundreds of neuroscience publications. Shared spaces promote translational research in addiction, depression, and resilience.
- Final Site Visit to the University of Michigan
The virtual site visit on July 11, 2025, reviewed two NIH-funded facilities at the University of Michigan (UM) that were supported by grants C06RR017514 and C06RR016573. Renovation of the Pharmacy Research Building created shared laboratories for the Center for Molecular Drug Targeting, enabling major growth in research productivity, recruitment of eight faculty members, support for 325 trainees, $79 million in funding, 634 publications, 47 patents, and several UM-affiliated startup companies. These activities continue producing long-lasting impact on research and economic outcomes. The Positron Emission Tomography Cyclotron Facility successfully replaced an outdated cyclotron; expanded radiochemistry capabilities; and supported extensive clinical and research programs, including U.S. Food and Drug Administration–approved radiopharmaceuticals, 479 publications, and 19 patents. The facility serves more than 30 personnel and numerous external investigators with $87 million in research funding, broadly benefiting research communities beyond the region.
- Final Site Visit to The University of Alabama at Birmingham
On July 9, 2025, ORIP staff conducted a virtual site visit to The University of Alabama at Birmingham (UAB) facilities renovated under NIH grants C06RR015490, C06RR017453, and C06RR020612. The multi-phased projects modernized Volker Hall’s animal research infrastructure by expanding nonhuman primate and small-animal housing, increasing cage sanitation capacity, and creating surgical and imaging suites and staff support areas. UAB met all project objectives, resulting in increased research capability, enhanced efficiency, and improved compliance with contemporary standards. The facilities now support more than 100 animal-use protocols, over 500 users, and research projects totaling $166 million. Renovations strengthened faculty recruitment, enabled workforce development programs, and led to significant downstream outcomes. These outcomes included 30 intellectual property disclosures, 78 patent applications, and 3 startup companies. Continued investments from UAB are planned, including a new biomedical research building and additional infrastructure upgrades after federal oversight ends.
- Notice of Change to the Instructions for Purpose and Scope in PAR-24-167, Utilizing Equipment to Study Environmental Extrinsic Factors and Enhance Rigor and Reproducibility of Animal Research (R24, Clinical Trials Not Allowed)
ORIP published a notice to inform potential applicants of changes to the language regarding the examples of projects that will not be supported under PAR-24-167, Utilizing Equipment to Study Environmental Extrinsic Factors and Enhance Rigor and Reproducibility of Animal Research (R24, Clinical Trials Not Allowed). ORIP supports the acquisition or update of modern equipment for measuring, monitoring, recording, and reporting environmental, biological, or biobehavioral variables.
- Site Visit: Purdue University
ORIP conducted a virtual site visit to Purdue University on June 20, 2025. NIH funded grant C06RR015480 for the renovation of offices and laboratories on the second, third, fourth, and fifth floors of the Robert Heine Pharmacy Building at Purdue University. Supported research areas include molecular pharmacology, medicinal chemistry, chemical biology, proteomics, development of inhalation products of antimicrobials, and pharmaceutical protein biotechnology.
Read more in the archive.
ORIP-Supported Research Highlights
- Imaging-Guided Deep Tissue In Vivo Sound Printing
Three-dimensional printing has shown promise for patient-specific implants and therapies but often requires invasive surgical procedures. This study introduces a novel platform called deep tissue in vivo sound printing (DISP), which uses injected ultrasound-responsive “bioinks” to fabricate complex bioprints deep within living tissues on demand. With ultrasound imaging offering precise targeting and real-time monitoring, DISP achieved high-resolution (~150 µm) and high-speed (up to 40 mm s-1) printing of functional biomaterials—including conductive hydrogels, cell-laden constructs, drug-loaded carriers, and bioadhesives—within mouse bladder and rabbit muscle in vivo (sex not specified). Biocompatibility was confirmed via histology, showing no signs of toxicity or adverse immune response. DISP offers promise for personalized implants, targeted drug delivery, and in situ bioelectronics and may revolutionize regenerative therapy for broad biomedical applications.
- Targeting SUMOylation Promotes cBAF Complex Stabilization and Disruption of the SS18::SSX Transcriptome in Synovial Sarcoma
Metastatic synovial sarcoma (SS) is an aggressive and incurable soft tissue sarcoma in children and young adults. Using human SS cell lines and genetically engineered mouse SS models (males only), researchers identified that SS models are significantly sensitive to genetic targeting of the SUMOylation pathway, which appears to affect chromatin structure and transcriptional function. The SS18::SSX fusion oncogene in SS elevates several SUMO pathway genes. Furthermore, subasumstat, a small-molecule SUMOylation inhibitor, leads to stabilization of the cBAF complex on chromatin and a shift away from the SS18::SSX-driven transcriptome, inducing DNA damage, cell death, and tumor inhibition. These results suggest SUMOylation as a therapeutic target in SS, inviting clinical evaluation of SUMO-pathway inhibitors in the treatment of this aggressive disease.
- Reprogramming Neuroblastoma by Diet-Enhanced Polyamine Depletion
Neuroblastoma, a highly lethal childhood cancer, is characterized by hyperactive MYC signaling and depends on local polyamine levels. Difluoromethylornithine (DFMO) was recently approved by the U.S. Food and Drug Administration for treatment of children with high-risk neuroblastoma, and combined treatment studies could improve therapeutic efficacy. DFMO inhibits the rate-limiting enzyme in polyamine synthesis, ornithine decarboxylase. This study in female mice demonstrates that combining a ProArg-free diet with DFMO dramatically reduces tumor polyamine levels. RNA sequencing, ribosome profiling, and proteomics analysis revealed that the combined treatment triggers ribosome stalling at codons ending in adenosine, shifts translation from proliferation genes to differentiation proteome, and markedly prolongs survival. This work suggests that diet and pharmacology can be used to target metabolic-translation coupling for treatment of neuroblastoma.
- Development and Validation of an Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Lenacapavir Plasma Concentrations: Application to Therapeutic Monitoring
Patients with multidrug-resistant HIV-1 infection are at increased risk for progression to AIDS, hospitalization, and death. Thus, clinicians must verify consistently adequate lenacapavir exposure over the dosing interval. In this study, the investigators developed and validated a novel mass spectrometry method to assess the effectiveness of antiretroviral therapy (ART) by quantifying lenacapavir concentrations in blank human plasma (sex not specified). With infrequent dosing of the first-in-class long-acting HIV-1 capsid inhibitor, ensuring adequate lenacapavir concentrations will be important, particularly to the treatment-experienced people living with HIV. By validating the assay design over a large, clinically relevant dosing range, the results revealed the fast, ultra-high-performance method achieved high precision and repeatability, suggesting that the new method can be used to monitor lenacapavir concentrations in human plasma and practically assess ART efficacy in clinical settings.
- SIV Infection Induces Alterations in Gene Expression and Loss of Interneurons in Rhesus Macaque Frontal Cortex During Early Systemic Infection
HIV infection affects the central nervous system and is associated with neurological symptoms. In this study, researchers reported that acute simian immunodeficiency virus (SIV) exposure triggers rapid, cell type–specific neurobiological injury in male and female rhesus macaques. Thousands of differentially expressed genes indicated strong interferon-driven immune activation at 10 days and enduring downregulation of neuronal pathways at 20 days. These findings suggest early interneuron loss and disrupted signaling may initiate long-term HIV-associated neurocognitive disorder (HAND). Overall, this study provides insight into the neuropathology of acute SIV infection and may inform new approaches for treating HAND.
Read more in the archive.
