Skip to main content

Filter Search Results

Publication Year

Animal Models

Topic Area

Methods

Funding Mechanism

Division of Comparative Medicine

Division of Construction and Instruments

Collaborating ICs

Selected Grantee Publications

Suppression of Viral Rebound by a Rev-Dependent Lentiviral Particle in SIV-Infected Rhesus Macaques

Hetrick et al., Gene Therapy. 2025.

https://pubmed.ncbi.nlm.nih.gov/39025983/

Viral reservoirs are a current major barrier that prevents an effective cure for patients with HIV. Antiretroviral therapy (ART) effectively suppresses viral replication, but ART cessation leads to viral rebound due to the presence of viral reservoirs. Researchers conducted in vivo testing of simian immunodeficiency virus (SIV) Rev-dependent vectors in SIVmac239-infected male and female Indian rhesus macaques, 3–6 years of age, to target viral reservoirs. Treatment with the SIV Rev-dependent vector reduced viral rebound and produced neutralizing antibodies following ART cessation. These results indicate the potential to self-control plasma viremia through a neutralizing antibody-based mechanism elicited by administration of Rev-dependent vectors. This research could guide future studies focused on investigating multiple vector injections and quantifying cell-mediated immune responses. Supported by ORIP (P51OD011104, P40OD028116), NIAID, and NIMH.

Single-Cell Transcriptomics Predict Novel Potential Regulators of Acute Epithelial Restitution in the Ischemia-Injured Intestine

Rose et al., American Journal of Physiology-Gastrointestinal and Liver Physiology. 2025.

https://pubmed.ncbi.nlm.nih.gov/39853303

Following ischemia in the small intestine, early barrier restoration relies on epithelial restitution to reseal the physical barrier and prevent sepsis. Pigs share a similar gastrointestinal anatomy, physiology, and microbiota with humans. Researchers used neonatal and juvenile, 2- to 6-week-old male and female Yorkshire cross pigs to determine upstream regulators of restitution. Single-cell sequencing of ischemia-injured epithelial cells demonstrated two sub-phenotypes of absorptive enterocytes, with one subset presenting a restitution phenotype. Colony-stimulating factor-1 (CSF1) was the only predicted upstream regulator expressed in juvenile jejunum compared with neonatal jejunum. An in vitro scratch wound assay using IPEC-J2 cells showed that BLZ945, a colony-stimulating factor 1 receptor antagonist, inhibited restitution. Ex vivo ischemia-injured neonatal pig jejunum treated with exogenous CSF1 displayed increased barrier function. This study could inform future research focused on developing novel therapeutics for intestinal barrier injury in patients. Supported by ORIP (T32OD011130, K01OD028207), NCATS, NICHD, and NIDDK.

Targeting Pancreatic Cancer Cell Stemness by Blocking Fibronectin-Binding Integrins on Cancer-Associated Fibroblasts

Wu et al., Cancer Research Communications. 2025.

https://pubmed.ncbi.nlm.nih.gov/39785683

Cancer-associated fibroblasts (CAFs) stimulate the formation and progression of pancreatic adenocarcinoma (PDAC) through the generation of extracellular matrix (ECM). Researchers developed a bispecific antibody (bsAb) that targets α5β1 and αvβ3 integrins expressed on CAFs. Blockade using the bsAb resulted in reduced assembly of fibronectin and collagen fibers in vitro. An antifibrotic effect was observed when CAFs were plated for 72 hours prior to bsAb treatment; pre-deposited ECM was disrupted. Six- to 8-week-old female nu/nu mice treated with bsAb demonstrated fewer tumors and reduced tumor stiffness compared with those exposed to only CAFs co-injected with PDAC cells. These results support a potential novel PDAC therapeutic that targets CAF-mediated fibronectin assembly and ECM production. Supported by ORIP (K01OD030513) and NCI.

Pre-Challenge Gut Microbial Signature Predicts RhCMV/SIV Vaccine Efficacy in Rhesus Macaques

Brochu et al., Microbiology Spectrum. 2025.

https://journals.asm.org/doi/10.1128/spectrum.01285-24

Rhesus cytomegalovirus–based simian immunodeficiency virus (RhCMV/SIV) vaccines provide protection against SIV challenge in approximately 60% of vaccinated rhesus macaques. This study assessed the role that gut microbiota play in SIV vaccine efficacy by analyzing the microbiomes of rhesus macaques before and after immunization using novel compositional data analysis techniques and machine-learning strategies. Researchers identified a gut microbial signature that predicted vaccine protection outcomes and correlated with early biomarker changes in the blood (i.e., host immune response to vaccination). This study indicates that the gut microbiome might play a role in vaccine-induced immunity. Supported by ORIP (P51OD011092).