Selected Grantee Publications
- Clear All
- 23 results found
- Neurological
- R24
Neuropeptide S Receptor 1 is a Nonhormonal Treatment Target in Endometriosis
Tapmeier et al., Science Translational Medicine. 2021.
https://pubmed.ncbi.nlm.nih.gov/34433639
Investigators analyzed genetic sequences of humans (n=32 families) and pedigree rhesus macaques (n=849) with spontaneous endometriosis to uncover potential targets for treatment. Target associations indicated a common insertion/deletion variant in NPSR1, the gene encoding neuropeptide S receptor 1. Immunocytochemistry, RT-PCR, and flow cytometry experiments indicated NPSR1 was expressed in the glandular epithelium of eutopic and ectopic endometrium. In a mouse model for endometriosis, an inhibitor of NPSR1-mediated signaling blocked proinflammatory TNFα release, monocyte chemotaxis, and inflammatory cell infiltrate. Further studies in nonhuman primates are needed; however, these results provide support for a nonhormonal treatment of endometriosis. Supported by ORIP (R24OD011173, P51OD011106).
Trim-Away Mediated Knock Down Uncovers a New Function for Lbh During Gastrulation of Xenopus laevis
Weir et al., Developmental Biology. 2021.
https://pubmed.ncbi.nlm.nih.gov/33159936/
The protein Lbh was identified as necessary for cranial neural crest cell migration in Xenopus. To investigate its role in embryonic events, the authors employed the technique "Trim-Away" to degrade this maternally deposited protein. Trim-Away utilizes the E3 ubiquitin ligase trim21 to degrade proteins targeted with an antibody. Early knockdown of Lbh in Xenopus results in defects in gastrulation that present with a decrease in fibronectin matrix assembly, an increase in mesodermal cell migration and decrease in endodermal cell cohesion. The technique is also effective on a second abundant maternal Protein Kinase C And Casein Kinase Substrate In Neurons 2. Supported by ORIP (R24OD021485) and NIDCR.
Endogenous Zebrafish Neural Cre Drivers Generated by CRISPR/Cas9 Short Homology Directed Targeted Integration
Almeida et al., Scientific Reports. 2021.
https://pubmed.ncbi.nlm.nih.gov/33462297/
Almeida et al. previously reported precision targeted integration of reporter DNA in zebrafish using CRISPR/Cas9. Here, they isolated zebrafish Cre recombinase drivers. A 2A-Cre recombinase transgene with 48 bp homology arms was targeted into proneural genes ascl1b, olig2 and neurod1. They observed high rates of germline transmission from 10 to 100% (10% olig2; 20% neurod1; 100% ascl1b). The lines Tg(ascl1b-2A-Cre)is75, Tg(olig2-2A-Cre)is76, and Tg(neurod1-2A-Cre)is77 expressed functional Cre recombinase in the cell populations. Results demonstrate Cre recombinase expression is driven by the native promoter and regulatory elements of targeted genes. This approach is a cost-effective method to generate cell type specific zebrafish Cre and CreERT2 drivers. Supported by ORIP (R24OD020166).