Selected Grantee Publications
- Clear All
- 201 results found
- HIV/AIDS
- Pediatrics
- Stem Cells/Regenerative Medicine
Transcriptomic Analysis of Skeletal Muscle Regeneration Across Mouse Lifespan Identifies Altered Stem Cell States
Walter et al., Nature Aging. 2024.
https://pubmed.ncbi.nlm.nih.gov/39578558
Age-related skeletal muscle regeneration dysfunction is poorly understood. Using single-cell transcriptomics and high-resolution spatial transcriptomics, researchers evaluated factors contributing to age-related decline in skeletal muscle regeneration after injury in young, old, and geriatric male and female mice (5, 20, and 26 months old). Eight immune cell types were identified and associated with age-related dynamics and distinct muscle stem cell states specific to old and geriatric tissue. The findings emphasize the role of extrinsic and intrinsic factors, including cellular senescence, in disrupting muscle repair. This study provides a spatial and molecular framework for understanding regenerative decline and cellular heterogeneity in aging skeletal muscle. Supported by ORIP (F30OD032097), NIA, NIAID, NIAMS, NICHD, and NIDA.
Immune Perturbation Following SHIV Infection Is Greater in Newborn Macaques Than in Infants
Shapiro et al., JCI Insight. 2024.
https://pubmed.ncbi.nlm.nih.gov/39190496
This study investigates immune perturbation following simian-human immunodeficiency virus (SHIV) infection in newborn and infant male and female rhesus macaques, highlighting significant differences in pathogenesis. Although plasma viremia and lymph node viral DNA were similar, newborns exhibited higher viral DNA levels in gut and lymphoid tissues 6–10 weeks postinfection than infants. Additionally, newborns showed greater immune alterations, with skewed monocyte and CD8+ T-cell profiles and minimal type I interferon responses. These findings suggest age-dependent immunological responses to SHIV and underscore the vulnerability of newborns to HIV-related pathogenesis, providing insights into immune development and pediatric HIV management. Supported by ORIP (P51OD011092, U42OD023038, U42OD010426) and NIAID.
Effect of Metabolic Status on Response to SIV Infection and Antiretroviral Therapy in Nonhuman Primates
Webb et al., JCI Insight. 2024.
https://pubmed.ncbi.nlm.nih.gov/39115937
This study examines how metabolic health influences the efficacy of antiretroviral therapy (ART). Using lean and obese male rhesus macaques, researchers explored the progression of simian immunodeficiency virus (SIV) infection. Obese macaques with metabolic dysfunction experienced more rapid disease progression and had a diminished response to ART than lean macaques. This study suggests metabolic health plays a significant role in HIV progression and treatment outcomes, highlighting the importance of managing metabolic conditions in people with HIV. Supported by ORIP (P51OD011092, S10OD025002), NIAID, and NIDDK.
Placental Gene Therapy in Nonhuman Primates: A Pilot Study of Maternal, Placental, and Fetal Response to Non-Viral, Polymeric Nanoparticle Delivery of IGF1
Wilson et al., Molecular Human Reproduction. 2024.
https://academic.oup.com/molehr/article/30/11/gaae038/7876288#493719584
This study investigates a novel nanoparticle-mediated gene therapy approach for addressing fetal growth restriction (FGR) in pregnant female nonhuman primates. Using polymer-based nanoparticles delivering a human insulin-like growth factor 1 (IGF1) transgene, the therapy targets the placenta via ultrasound-guided injections. Researchers evaluated maternal, placental, and fetal responses by analyzing tissues, immunomodulatory proteins, and hormones (progesterone and estradiol). Findings highlight the potential of IGF1 nanoparticles to correct placental insufficiency by enhancing fetal growth, providing a groundbreaking advancement for in utero treatments. This research supports further exploration of nonviral gene therapies for improving pregnancy outcomes and combating FGR-related complications. Supported by ORIP (P51OD011106) and NICHD.
Engineered Deletions of HIV Replicate Conditionally to Reduce Disease in Nonhuman Primates
Pitchai et al., Science. 2024.
https://pubmed.ncbi.nlm.nih.gov/39116226/
Current antiretroviral therapy (ART) for HIV is limited by the necessity for continuous administration. Discontinuation of ART leads to viral rebound. A therapeutic interfering particle (TIP) was developed as a novel single-administration HIV therapy using defective interfering particles. TIP treatment in two humanized mouse models demonstrated a significant reduction in HIV viral load. TIP intervention was completed 24 hours prior to a highly pathogenic simian immunodeficiency virus (SIV) challenge in a nonhuman primate (NHP) rhesus macaque infant model. Compared to untreated SIV infection, NHPs that received TIP treatment displayed no visible signs of SIV-induced AIDS and exhibited improved seroconversion and a significant survival advantage to the 30-week clinical endpoint. Peripheral blood mononuclear cells isolated from HIV-infected patients showed that TIP treatment reduced HIV outgrowth. This study demonstrates the potential use of a single-administration TIP for HIV treatment. Supported by ORIP (P51OD011092, U42OD010426), NCI, NIAID, and NIDA.