Selected Grantee Publications
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- 6 results found
- Aquatic Vertebrate Models
- Cancer
- Infectious Diseases
Temperature-Dependent Alterations in the Proteome of the Emergent Fish Pathogen Edwardsiella piscicida
Jacobsen et al., Journal of Fish Diseases. 2024.
https://pubmed.ncbi.nlm.nih.gov/39304982
Reported outbreaks of Edwardsiella piscicida, a bacterial pathogen among cultured and wild fish, have been steadily increasing over the past decade in tandem with climate change–mediated increases in water temperatures. The capacity for this increasingly prevalent fish pathogen to infect and cause disease in mammals is important to understand. Researchers examined the role of temperature on the virulence of E. piscicida to understand its pathogenesis in the context of climate warming trends and better understand its zoonotic potential. Findings revealed downregulation of virulence-related proteins, such as flagellar and Type VI secretion system proteins, at colder temperatures. These findings highlight the potential environmental factors influencing the pathogen’s threat to aquaculture and public health. Supported by ORIP (S10OD026918, T32OD011147).
Early Detection of Pseudocapillaria tomentosa by qPCR in Four Lines of Zebrafish, Danio rerio (Hamilton 1882)
Schuster et al., Journal of Fish Diseases. 2023.
https://onlinelibrary.wiley.com/doi/10.1111/jfd.13773
The intestinal nematode Pseudocapillaria tomentosa in zebrafish (Danio rerio) causes profound intestinal lesions, emaciation, and death and is a promoter of a common intestinal cancer in zebrafish. This nematode has been detected in an estimated 15% of zebrafish laboratories. Adult worms are readily detected about 3 weeks after exposure by either histology or wet mount preparations of the intestine, and larval worms are inconsistently observed in fish before this time. A quantitative PCR (qPCR) test was recently developed to detect the worm in fish and water, and here the authors determined that the test on zebrafish intestines was effective for earlier detection. Supported by ORIP (R24OD010998, P40OD011021).
Rbbp4 Loss Disrupts Neural Progenitor Cell Cycle Regulation Independent of Rb and Leads to Tp53 Acetylation and Apoptosis
Schultz-Rogers et al., Developmental Dynamics. 2022.
https://www.doi.org/10.1002/dvdy.467
Retinoblastoma binding protein 4 (Rbbp4) is a component of transcription regulatory complexes that control cell cycle gene expression by cooperating with the Rb tumor suppressor to block cell cycle entry. The authors used genetic analysis to examine the interactions of Rbbp4, Rb, and Tp53 in zebrafish neural progenitor cell cycle regulation and survival. Rbbp4 is upregulated across the spectrum of human embryonal and glial brain cancers, and it is essential for zebrafish neurogenesis. Rbbp4 loss leads to apoptosis and γ-H2AX in the developing brain that is suppressed by tp53 knockdown or maternal zygotic deletion. Mutant retinal neural precursors accumulate in M phase and fail to initiate G0 gene expression. Rbbp4; Rb1 double mutants show an additive effect on the number of M phase cells. The study demonstrates that Rbbp4 is necessary for neural progenitor cell cycle progression and initiation of G0, independent of Rb, and suggests that Rbbp4 is required for cell cycle exit and contributes to neural progenitor survival. Supported by ORIP (R24OD020166) and NIGMS.
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.
The SARS-CoV-2 Receptor and Other Key Components of the Renin-Angiotensin-Aldosterone System Related to COVID-19 are Expressed in Enterocytes in Larval Zebrafish
Postlethwait et al., Biology Open. 2021.
https://bio.biologists.org/content/10/3/bio058172.article-info
Hypertension and respiratory inflammation are exacerbated by the Renin-Angiotensin-Aldosterone System (RAAS), which normally protects from dropping blood pressure via Angiotensin II (Ang II) produced by the enzyme Ace. The Ace paralog Ace2 degrades Ang II and serves as the SARS-CoV-2 receptor. To exploit zebrafish to understand the relationship of RAAS to COVID-19, the group conducted genomic and phylogenetic analyses. Results identified a type of enterocyte as the expression site of zebrafish orthologs of key RAAS components, including the SARS-CoV-2 co-receptor. Results identified vascular cell subtypes expressing Ang II receptors and identified cell types to exploit zebrafish as a model for understanding COVID-19 mechanisms. Supported by ORIP (R24OD026591, R01OD011116), NIGMS, NICHD.
Intra-Strain Genetic Variation of Platyfish (Xiphophorus maculatus) Strains Determines Tumorigenic Trajectory
Lu et al., Frontiers in Genetics . 2020.
https://www.frontiersin.org/articles/10.3389/fgene.2020.562594/full
Xiphophorus interspecies hybrids represent a valuable model system to study heritable tumorigenesis. Although the ancestors of the two X. maculatus parental lines, Jp163 A and Jp163 B, were siblings produced by the same mother, backcross interspecies hybrid progeny between X. hellerii and X. maculatus Jp163 A develop spontaneous melanoma initiating at the dorsal fin due to a regulator encoded by the X. maculatus genome; the backcross hybrid progeny with X. hellerii or X. couchianus and Jp163 B exhibit melanoma on their flanks. Comparative genomic analyses revealed genetic differences are associated with pathways highlighting fundamental cellular functions. Disruption of these baselines may give rise to spontaneous or inducible tumorigenesis. Supported by ORIP (R24OD011120), NCI, and NIGMS.