Browsing by Author "Perry, Blair W."

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    Growth and stress response mechanisms underlying post- feeding regenerative organ growth in the Burmese python
    (BMC, 2017) Andrew, Audra L.; Perry, Blair W.; Card, Daren C.; Schield, Drew R.; Ruggiero, Robert P.; McGaugh, Suzanne E.; Choudhary, Amit; Secor, Stephen M.; Castoe, Todd A.; University of Texas Arlington; University of Minnesota Twin Cities; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Alabama Tuscaloosa
    Background: Previous studies examining post-feeding organ regeneration in the Burmese python (Python molurus bivittatus) have identified thousands of genes that are significantly differentially regulated during this process. However, substantial gaps remain in our understanding of coherent mechanisms and specific growth pathways that underlie these rapid and extensive shifts in organ form and function. Here we addressed these gaps by comparing gene expression in the Burmese python heart, liver, kidney, and small intestine across pre- and post-feeding time points (fasted, one day post-feeding, and four days post-feeding), and by conducting detailed analyses of molecular pathways and predictions of upstream regulatory molecules across these organ systems. Results: Identified enriched canonical pathways and upstream regulators indicate that while downstream transcriptional responses are fairly tissue specific, a suite of core pathways and upstream regulator molecules are shared among responsive tissues. Pathways such as mTOR signaling, PPAR/LXR/RXR signaling, and NRF2-mediated oxidative stress response are significantly differentially regulated in multiple tissues, indicative of cell growth and proliferation along with coordinated cell-protective stress responses. Upstream regulatory molecule analyses identify multiple growth factors, kinase receptors, and transmembrane receptors, both within individual organs and across separate tissues. Downstream transcription factors MYC and SREBF are induced in all tissues. Conclusions: These results suggest that largely divergent patterns of post-feeding gene regulation across tissues are mediated by a core set of higher-level signaling molecules. Consistent enrichment of the NRF2-mediated oxidative stress response indicates this pathway may be particularly important in mediating cellular stress during such extreme regenerative growth.
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    Identification of an integrated stress and growth response signaling switch that directs vertebrate intestinal regeneration
    (BMC, 2022) Westfall, Aundrea K.; Perry, Blair W.; Kamal, Abu H. M.; Hales, Nicole R.; Kay, Jarren C.; Sapkota, Madhab; Schield, Drew R.; Pellegrino, Mark W.; Secor, Stephen M.; Chowdhury, Saiful M.; Castoe, Todd A.; University of Texas Arlington; Baylor College of Medicine; University of North Texas Denton; University of Alabama Tuscaloosa; University of Texas Southwestern Medical Center Dallas
    Background: Snakes exhibit extreme intestinal regeneration following months-long fasts that involves unparalleled increases in metabolism, function, and tissue growth, but the specific molecular control of this process is unknown. Understanding the mechanisms that coordinate these regenerative phenotypes provides valuable opportunities to understand critical pathways that may control vertebrate regeneration and novel perspectives on vertebrate regenerative capacities. Results: Here, we integrate a comprehensive set of phenotypic, transcriptomic, proteomic, and phosphoproteomic data from boa constrictors to identify the mechanisms that orchestrate shifts in metabolism, nutrient uptake, and cellular stress to direct phases of the regenerative response. We identify specific temporal patterns of metabolic, stress response, and growth pathway activation that direct regeneration and provide evidence for multiple key central regulatory molecules kinases that integrate these signals, including major conserved pathways like mTOR signaling and the unfolded protein response. Conclusion: Collectively, our results identify a novel switch-like role of stress responses in intestinal regeneration that forms a primary regulatory hub facilitating organ regeneration and could point to potential pathways to understand regenerative capacity in vertebrates.
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    Multi-species comparisons of snakes identify coordinated signalling networks underlying post-feeding intestinal regeneration
    (Royal Society of London, 2019) Perry, Blair W.; Andrews, Audra L.; Kamal, Abu Hena Mostafa; Card, Daren C.; Schield, Drew R.; Pasquesi, Giulia I. M.; Pellegrino, Mark W.; Mackessy, Stephen P.; Chowdhury, Saiful M.; Secor, Stephen M.; Castoe, Todd A.; University of Texas Arlington; University of Northern Colorado; University of Alabama Tuscaloosa
    Several snake species that feed infrequently in nature have evolved the ability to massively upregulate intestinal form and function with each meal. While fasting, these snakes downregulate intestinal form and function, and upon feeding restore intestinal structure and function through major increases in cell growth and proliferation, metabolism and upregulation of digestive function. Previous studies have identified changes in gene expression that underlie this regenerative growth of the python intestine, but the unique features that differentiate this extreme regenerative growth from non-regenerative post-feeding responses exhibited by snakes that feed more frequently remain unclear. Here, we leveraged variation in regenerative capacity across three snake species-two distantly related lineages (Crotalus and Python) that experience regenerative growth, and one (Nerodia) that does not-to infer molecular mechanisms underlying intestinal regeneration using transcriptomic and proteomic approaches. Using a comparative approach, we identify a suite of growth, stress response and DNA damage response signalling pathways with inferred activity specifically in regenerating species, and propose a hypothesis model of interactivity between these pathways that may drive regenerative intestinal growth in snakes.