Selected Grantee Publications
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Spatiotemporal Characterization of Cyclooxygenase Pathway Enzymes During Vertebrate Embryonic Development
Leathers et al., Developmental Biology. 2025.
https://pubmed.ncbi.nlm.nih.gov/39581452/
The cyclooxygenase (COX) pathway plays a fundamental role in embryonic development. Disruptions of the COX pathway during pregnancy cause developmental anomalies, including craniofacial clefts, impaired gut innervation, and neural tube defects in the embryo. Researchers used Gallus gallus embryos to study the expression of COX pathway enzymes during neurulation. COX-1 protein expression was upregulated in cells undergoing mitosis, whereas COX-2 protein expression was ubiquitous. This study provides spatiotemporal expression data of COX pathway enzymes at key embryonic development stages in G. gallus and guides future studies focused on defining the role of these enzymes during embryonic development. Supported by ORIP (T35OD010956), NEI, NIDCR, and NIGMS.
Identifying Mitigating Strategies for Endothelial Cell Dysfunction and Hypertension in Response to VEGF Receptor Inhibitors
Camarda et al., Clinical Science. 2024.
https://pubmed.ncbi.nlm.nih.gov/39282930/
Vascular endothelial growth factor receptor inhibitor (VEGFRi) use can improve survival in patients with advanced solid tumors, but outcomes can worsen because of VEGFRi-induced hypertension, which can increase the risk of cardiovascular mortality. The underlying pathological mechanism is attributed to endothelial cell (EC) dysfunction. The researchers performed phosphoproteomic profiling on human ECs and identified α-adrenergic blockers, specifically doxazosin, as candidates to oppose the VEGFRi proteomic signature and inhibit EC dysfunction. In vitro testing of doxazosin with mouse, canine, and human aortic ECs demonstrated EC-protective effects. In a male C57BL/6J mouse model with VEGFRi-induced hypertension, it was demonstrated that doxazosin prevents EC dysfunction without decreasing blood pressure. In canine cancer patients, both doxazosin and lisinopril improve VEGFRi-induced hypertension. This study demonstrates the use of phosphoproteomic screening to identify EC-protective agents to mitigate cardio-oncology side effects. Supported by ORIP (K01OD028205), NCI, NHGRI, and NIGMS.
Proteomic Profiling of Extracellular Vesicles Isolated From Plasma and Peritoneal Exudate in Mice Induced by Crotalus scutulatus scutulatus Crude Venom and Its Purified Cysteine-Rich Secretory Protein (Css-CRiSP)
Reyes et al., Toxins (Basel). 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10467150/
Toxins in viperid snakes can induce clinically heterogeneous effects, but most viper venoms are composed of only 10 main protein families. Researchers investigated the proteome expression profile of extracellular vesicles isolated from biofluid samples from male and female mice after injection with crude venom and cysteine-rich secretory proteins. They reported changes in the expression of proteins involved in cell adhesion, cytoskeleton rearrangement, signal transduction, immune responses, and vesicle-mediated transports. This work could be applied in future efforts for early detection and assessment of local effects. Supported by ORIP (P40OD010960), NIGMS, and NHLBI.
Promoting Validation and Cross-Phylogenetic Integration in Model Organism Research
Cheng et al., Disease Models & Mechanisms. 2022.
https://www.doi.org/10.1242/dmm.049600
Model organisms are essential for biomedical research and therapeutic development, but translation of such research to the clinic is low. The authors summarized discussions from an NIH virtual workshop series, titled “Validation of Animal Models and Tools for Biomedical Research,” held from 2020 to 2021. They described challenges and opportunities for developing and integrating tools and resources and provided suggestions for improving the rigor, validation, reproducibility, and translatability of model organism research. Supported by ORIP (R01OD011116, R24OD031447, R03OD030597, R24OD018559, R24OD017870, R24OD026591, R24OD022005, U42OD026645, U42OD012210, U54OD030165, UM1OD023221, P51OD011107), NIAMS, NIDDK, NIGMS, NHGRI, and NINDS.