Programs and Activities Highlights
- 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 The Positron Emission Tomography Cyclotron Facility successfully replaced an outdated cyclotron; expanded radiochemistry capabilities; and supported extensive clinical and research programs, including U.S. Food and Drug Administration–approved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.
- Site Visit: University of New Mexico
ORIP conducted a virtual site visit to the University of New Mexico (UNM) on June 20, 2025. NIH funded grant C06RR017566 for the construction of a multimodal neuroimaging facility for animal research on neurological and psychiatric disorders at UNM’s Health Sciences Center (HSC). C06RR016492 supported the renovation of the second floor of the new multidisciplinary research facility for the Toxicology and Environmental Diseases program in the College of Pharmacy at UNM HSC. C06RR018888 funded the construction of the neurobiology building to support the clinical and translational research programs of the psychiatry and neurology departments at UNM HSC.
Read more in the archive.
ORIP-Supported Research Highlights
- 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.
- Computational Design of Sequence-Specific DNA-Binding Proteins
The investigators used computational modeling to design small proteins that recognize specific DNA sequences. They first generated a library of small proteins that could bind to the backbone of DNA and further refined this library to account for specific differences in base pairs; then they used iterative rounds of sequence optimization to design the final protein. These protein–DNA structures were then crystallized. The researchers compared the computational models with the crystal structures and reported excellent agreement. These DNA-binding proteins were then tested in cells, showing that they are capable of either suppressing or activating transcription. This in silico custom DNA design method showed potential applications in gene regulation and editing.
- Programmable Protein Ligation on Cell Surfaces
The unique protein dynamics on the cell surface are often altered with disease. Researchers developed a synthetic biology system called SMART (splicing-modulated actuation upon recognition of targets) that can distinguish these cell surface features. They demonstrated that SMART allowed a controlled “decoration” of cells with diverse proteins—including enzymes, fluorescent reporters, and binding domains—without requiring harsh chemicals or disrupting cell viability. This highly selective method works across multiple cell types and maintains the biological activity of both the surface protein and the attached payload. This system may offer applications for future studies that involve cell engineering, as well as mechanistic studies of cell-surface signaling and interactions.
- Magnetically Labelled iPSC-Derived Extracellular Vesicles Enable MRI/MPI-Guided Regenerative Therapy for Myocardial Infarction
Stem cell–based therapies have shown promise for treating heart diseases, which are a leading cause of death and a global public health burden. Researchers used stem cell–derived extracellular vesicles (EVs) filled with superparamagnetic iron oxide (SPEVs) as imaging contrast agents for imaging-guided regenerative treatment of heart attacks. While manipulating and imaging EVs is challenging in a clinical setting, the researchers were able to detect these new SPEVs using magnetic resonance imaging and magnetic particle tracking imaging in female mice. They showed that both native EVs and their engineered SPEVs significantly improved cardiac function and dramatically decreased scar size. The study demonstrated that the engineered SPEVs offer a novel, cell-free approach for cardiovascular regenerative medicine with both noninvasive imaging-tracking capabilities and therapeutic benefits for heart repair.
- Distinct CD8+ T Cell Dynamics Associate with Response to Neoadjuvant Cancer Immunotherapies
Recent advances in monoclonal antibodies have transformed cancer treatments, but more work is needed to predict responses to immune checkpoint inhibitors (ICIs) (treatments that help the immune system recognize and attack cancer cells). In this study, researchers tested combinations of three ICIs—anti-PD-1 (nivolumab; Nivo) alone, nivolumab plus CTLA-4 (ipilimumab; Ipi), and nivolumab plus LAG-3 (relatlimab; Rela)—in a cohort of patients (both sexes included) with head and neck squamous cell carcinoma (NCT04080804). They found that the two combination therapies may enable higher pathologic response rates than nivolumab alone. These combination regimens target specific CD8+ T-cell states within the tumor microenvironment. Nivo+Rela, but not Nivo+Ipi, induces widespread T-cell receptor sharing among transcriptional states, as well as T-cell receptor diversity in patients who respond to therapy. This work may provide biomarkers that could play a crucial role in tailoring therapies to patient profiles.
Read more in the archive.
