Selected Grantee Publications
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- 3 results found
- Rodent Models
- Cancer
- 2021
An NR2F1-Specific Agonist Suppresses Metastasis by Inducing Cancer Cell Dormancy
Khalil et al., The Journal of Experimental Medicine. 2021.
Researchers described the discovery of a nuclear receptor NR2F1 antagonist that specifically activates dormancy programs in malignant cells. Agonist treatment resulted in a self-regulated increase in NR2F1 mRNA and protein and downstream transcription of a novel dormancy program. This program led to growth arrest in multiple human cell lines, as well as patient-derived organoids. This effect was lost when NR2F1 was knocked out. In mice, agonist treatment resulted in inhibition of lung metastasis of head and neck squamous cell carcinomas, even after cessation of the treatment. This work provides proof of principle supporting the use of NR2F1 agonists to induce dormancy as a therapeutic strategy to prevent metastasis. Supported by ORIP (S10OD018522 and S10OD026880) and others.
Sexual Dimorphic Impact of Adult-Onset Somatopause on Life Span and Age-Induced Osteoarthritis
Poudel et al., Aging Cell. 2021.
https://pubmed.ncbi.nlm.nih.gov/?term=Poudel%20SB&cauthor_id=34240807
Osteoarthritis (OA) is a major cause of disability worldwide. In humans, the age-associated decline in growth hormone (GH) levels was hypothesized to play a role in the etiology of OA. Investigators studied the impact of adult-onset isolated GH deficiency (AOiGHD) on the life span and skeletal integrity in aged mice. Reductions in GH during adulthood were associated with extended life span and reductions in body temperature in female mice only. However, end-of-life pathology revealed high levels of lymphomas in both sexes, independent of GH status. Skeletal characterization revealed increases in OA severity in AOiGHD mice. In conclusion, while their life span increased, AOiGHD female mice’s health span was compromised by high-grade lymphomas and the development of severe OA. In contrast, AOiGHD males, which did not show extended life span, showed an overall low grade of lymphomas but exhibited significantly decreased health span, evidenced by increased OA severity. Supported by ORIP (S10OD010751) and others.
Identification of Basp1 as a Novel Angiogenesis-regulating Gene by Multi-Model System Studies
Khajavi et al., FASEB Journal. 2021.
https://pubmed.ncbi.nlm.nih.gov/33899275/
The authors previously used genetic diversity in inbred mouse strains to identify quantitative trait loci (QTLs) responsible for differences in angiogenic response. Employing a mouse genome-wide association study (GWAS) approach, the region on chromosome 15 containing Basp1 was identified as being significantly associated with angiogenesis in inbred strains. To investigate its role in vivo, they knocked out basp1 in transgenic kdrl:zsGreen zebrafish embryos using a widely adopted CRISPR-Cas9 system. They further showed that basp1 promotes angiogenesis by upregulating β-catenin gene and the Dll4/Notch1 signaling pathway. These results provide the first in vivo evidence to indicate the role of basp1 as an angiogenesis-regulating gene. Supported by ORIP (R24OD017870) and NEI.