Selected Grantee Publications
- 486 results found
Cytomegalovirus Infection Facilitates the Costimulation of CD57+CD28- CD8 T Cells in HIV Infection and Atherosclerosis via the CD2–LFA-3 Axis
Winchester et al., Journal of Immunology. 2024.
https://pubmed.ncbi.nlm.nih.gov/38047900/
People with HIV are at increased risk of developing atherosclerosis and other cardiovascular diseases, and HIV coinfection with cytomegalovirus (CMV) is associated with immune activation and inflammation. In this study, researchers explored the role of the CD2–LFA-3 axis in driving activation and proliferation of CD57+CD28- CD8 T cells using clinical samples from patients with or without HIV. They propose a model in which CMV infection is linked to enhanced CD2 expression on the T cells, enabling the activation via LFA-3 signals and potentially leading to cardiopathogenic interactions with vascular endothelial cells that express LFA-3. This work provides a potential therapeutic target in atherosclerosis development and progression, especially for people with HIV. Supported by ORIP (P51OD011132, U24OD011023) and NIAID.
Antibiotic-Induced Gut Dysbiosis Elicits Gut–Brain–Axis Relevant Multi-Omic Signatures and Behavioral and Neuroendocrine Changes in a Nonhuman Primate Model
Hayer et al., Gut Microbes. 2024.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826635/
Gut microbiome–mammalian cell interactions influence the development of metabolic, immune-mediated, and neuropsychiatric disorders. Dysbiosis of the gut microbiome has been linked to behavioral characteristics in previous nonhuman primate (NHP) studies, but additional studies using NHPs are necessary to understand microbiota–gut–brain communication. The authors sought to evaluate whether antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut–brain axis disruption in common marmosets of both sexes. For the first time in an NHP model, this study demonstrated that antibiotics induce gut dysbiosis, alter gut metabolites relevant to gut–brain communication, affect neuroendocrine responses in response to stressful stimuli, and change social behavior. Supported by ORIP (K01OD030514), NCI, and NIGMS.
A Single-Cell Time-Lapse of Mouse Prenatal Development From Gastrula to Birth
Qiu et al., Nature. 2024.
https://pubmed.ncbi.nlm.nih.gov/38355799/
In this study, investigators combined single-cell transcriptome profiling of male and female mouse embryos and newborn pups with previously published data to construct a tree of cell-type relationships tracing development from zygote to birth. They applied optimized single-cell combinatorial indexing to profile the transcriptional states of 12.4 million nuclei from 83 embryos, precisely staged at 2- to 6-hour intervals spanning late gastrulation to birth; establish a global framework for exploring mammalian development; and construct a rooted tree of cell-type relationships, from zygote to birth. Their analysis allowed them to systematically nominate genes that encode transcription factors and other proteins as candidate drivers of the in vivo differentiation of hundreds of cell types. Extending this framework to postnatal time points could yield a single-cell time-lapse of the entire mammalian life span, from conception to death. Supported by ORIP (UM1OD023222) and NHGRI.
Preclinical Safety and Biodistribution of CRISPR Targeting SIV in Non-Human Primates
Burdo et al., Gene Therapy. 2024.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11090835/
Nonhuman primates have served as a valuable resource for evaluating novel eradication and cure strategies for HIV infection. Using a male rhesus macaque model, researchers demonstrated the safety and utility of CRISPR gene-editing technology for targeting integrated simian immunodeficiency virus (SIV). Their work suggests that a single intravenous inoculation for HIV gene editing can be utilized to reach viral reservoirs throughout the body. Additionally, no off-target effects or abnormal pathology were observed. Together, these findings support the continued development of HIV eradicative cure strategies using CRISPR technology in humans. Supported by ORIP (P40OD012217, U42OD021458).
Establishment of a Practical Sperm Cryopreservation Pathway for the Axolotl (Ambystoma mexicanum): A Community-Level Approach to Germplasm Repository Development
Coxe et al., Animals (Basel). 2024.
https://pubmed.ncbi.nlm.nih.gov/38254376/
The axolotl (Ambystoma mexicanum) is an important biomedical research model for organ regeneration, but housing and maintaining live animals is expensive and risky as new transgenic lines are developed. The authors report an initial practical pathway for sperm cryopreservation to support germplasm repository development. They assembled a pathway through the investigation of axolotl sperm collection by stripping, refrigerated storage in various osmotic pressures, cryopreservation in various cryoprotectants, and in vitro fertilization using thawed sperm. This work is the first report of successful production of axolotl offspring with cryopreserved sperm and provides a general framework for pathway development to establish Ambystoma germplasm repositories for future research and applications. Supported by ORIP (R24OD010441, R24OD028443, P40OD019794).
The Gene Expression Profile and Cell of Origin of Canine Peripheral T-Cell Lymphoma
Owens et al., BMC Cancer. 2024.
https://pubmed.ncbi.nlm.nih.gov/38166662/
Peripheral T-cell lymphoma (PTCL) refers to a heterogenous group of T-cell neoplasms with poor treatment responses and survival times. Canine PTCL clinically and immunophenotypically resembles the most common human subtype, PTCL-NOS (PTCL-not otherwise specified), and is a naturally occurring model for human PTCL. Gene expression profiling in human PTCL-NOS has helped characterize this ambiguous diagnosis into distinct subtypes, but similar gene expression profiling in canine PTCL is lacking. Canine CD4+ PTCL most closely resembles the GATA3-PTCL subtype of PTCL-NOS and may originate from an earlier stage of T-cell development than the more conventionally posited mature T-helper cell origin. Supported by ORIP (T32OD010437).
Newly Identified Roles for PIEZO1 Mechanosensor in Controlling Normal Megakaryocyte Development and in Primary Myelofibrosis
Abbonante et al., American Journal of Hematology. 2024.
https://pubmed.ncbi.nlm.nih.gov/38165047/
Mechanisms through which mature megakaryocytes (Mks) and their progenitors sense the bone marrow extracellular matrix to promote lineage differentiation are only partially understood. The authors report that PIEZO1, a mechanosensitive cation channel, is expressed in mouse and human Mks, and activation of PIEZO1 increased the number of immature Mks in mice. Piezo1/2 knockout mice show an increase in Mk size and platelet count, both at basal state and upon marrow regeneration. Together, these data suggest that PIEZO1 places a brake on Mk maturation and platelet formation in physiology, and its upregulation might contribute to aggravating disease. Supported by ORIP (K01OD025290), NHGRI, NHLBI, and NCATS.
Conduction-Dominated Cryomesh for Organism Vitrification
Guo et al., Advanced Science. 2024.
https://pubmed.ncbi.nlm.nih.gov/38018294/
Vitrification-based cryopreservation via cryomesh is a promising approach for maintaining biodiversity, health care, and sustainable food production via long-term preservation of biological systems. Here, researchers conducted a series of experiments aimed at optimizing the cooling and rewarming rates of cryomesh to increase the viability of various cryopreserved biosystems. They found that vitrification was significantly improved by increasing thermal conductivity, reducing mesh wire diameter and pore size, and minimizing the nitrogen vapor barrier of the conduction-dominated cryomesh. Cooling rates increased twofold to tenfold in a variety of biosystems. The conduction-dominated cryomesh improved the cryopreservation outcomes of coral larvae, Drosophila embryos, and zebrafish embryos by vitrification. These findings suggest that the conduction-dominated cryomesh can improve vitrification in such biosystems for biorepositories, agriculture and aquaculture, and research. Supported by ORIP (R24OD028444, R21OD028758, R24OD034063, R21OD028214), NIDDK, and NIGMS.
The Monarch Initiative in 2024: An Analytic Platform Integrating Phenotypes, Genes and Diseases Across Species
Putman et al., Nucleic Acids Research. 2024.
https://pubmed.ncbi.nlm.nih.gov/38000386/
The Monarch Initiative aims to bridge the gap between the genetic variations, environmental determinants, and phenotypic outcomes critical for translational research. The Monarch app provides researchers access to curated data sets with information on genes, phenotypes, and diseases across species and advanced analysis tools for such diverse applications as variant prioritization, deep phenotyping, and patient profile matching. Researchers describe upgrades to the app, including scalable cloud-based infrastructure, simplified data ingestion and knowledge graph integration systems, enhanced data mapping and integration standards, and a new user interface with novel search and graph navigation features. A customized plugin for OpenAI’s ChatGPT allows the use of large language models to interrogate knowledge in the Monarch graph and increase the reliability of the responses of Monarch’s analytic tools. These upgrades will enhance clinical diagnosis and the understanding of disease mechanisms. Supported by ORIP (R24OD011883), NLM, and NHGRI.
Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population
Cruz Cisneros et al., Vaccines. 2024.
https://pubmed.ncbi.nlm.nih.gov/38276675/
The COVID-19 pandemic led to the rapid and worldwide development of highly effective vaccines against SARS-CoV-2. Although host genetic factors are known to affect vaccine efficacy for such respiratory pathogens as influenza and tuberculosis, the impact of host genetic variation on vaccine efficacy against COVID-19 is not well understood. Investigators used the diversity outbred mouse model to study the effects of genetic variation on vaccine efficiency. Data indicate that variations in vaccine response in mice are heritable, similar to that in human populations. Supported by ORIP (U42OD010924), NIAID, and NIGMS.