Biology subjects

Sanchez, C. A.

Publications and source records attributed to Sanchez, C. A..

5 recordsLinked to original sources

bioRxiv2025

The macroecology of viral coinfection

Coinfection is common in wild animals, and can profoundly influence disease outcomes and transmission. However, most coinfection research is based on laboratory experiments or a few well-studied wildlife systems. Here, we use data from the PREDICT project - the largest standardized wildlife disease surveillance project ever conducted - to describe patterns of viral coinfection and evaluate their association with host and virus factors. Within the viruses prioritized for testing, we find that coinfection is rare (detected in just 223 of 65,662 animals), but still more common than expected by chance - especially coinfections of coronaviruses, paramyxoviruses, and influenza A virus. We further find that coinfection is associated with host age, but bats and rodents exhibit opposing relationships. We find that captive wild animals (specifically rats and mallards) exhibit higher coinfection than free-ranging wild animals, highlighting potential risks to wildlife and human health from the wildlife trade. Finally, we find that biases in sampling and testing can shape observed patterns of coinfection. Our results characterize associations among viruses in the largest relevant dataset currently available. Factors associated with coinfection in this dataset such as host-level variation, virus-virus interactions, and human interference should be further tested via surveillance and laboratory approaches to better resolve the role of coinfection as an important and likely overlooked driver of viral dynamics in nature.

ecology↗

bioRxiv2025

Role of NLRP3 activation in salt sensitive blood pressure regulation, effect of ND-13

Background and ObjectivesHigh salt intake is a major contributor to the development and exacerbation of hypertension, partly by inducing an inflammatory response through immune cell dysfunction. Inflammasomes, key components of the innate immune response, may influence blood pressure regulation. The renal DJ-1 protein is known for its antioxidant and anti-inflammatory properties. To explore novel pharmacological applications of renal DJ-1 pathway, we developed ND-13, a peptide consisting of 13 highly conserved amino acids derived from the DJ-1 sequence. In this study, we investigated the effects of ND-13 and MCC950, a specific NLRP3 inflammasome inhibitor, on blood pressure regulation in C57BL/6J mice on a high-salt diet. MethodsC57BL/6J mice were fed a high-salt diet (HS) for one week and then treated with ND-13 or MCC950, an NLRP3 inflammasome inhibitor. Subsequently, gene expression by qPCR, staining of immune cells, Sirius Red and Periodic Acid-Schiff (PAS) staining were determined in the mice kidneys, as well as the inflammasome activity in peritoneal cells. ResultsOne week of HS resulted increased in blood pressure, that was prevented by both ND-13 and MCC950 treatments. These treatments also prevented the increase in proteinuria that was accompanied by tubular protein deposits. Renal expression of inflammatory genes, immune cell infiltration, and renal collagen deposition were not observed in the HS group. Peritoneal macrophages isolated from HS treated mice exhibited enhanced IL-1{beta} release upon LPS+ATP stimulation, suggesting activation of the NLRP3 inflammasome. Treatment with ND-13 and MCC950 normalized this activity. Furthermore, ND-13 reduced IL-1{beta} mRNA expression in peritoneal macrophages. ConclusionsOur findings highlight the critical role of the NLRP3 inflammasome in salt-sensitive blood pressure regulation and suggest that ND-13 may serve as a potential therapeutic agent for preventing hypertension and associated inflammatory alterations induced by a high salt intake.

physiology↗

bioRxiv2022

Extrachromosomal DNA in the cancerous transformation of Barrett's esophagus

BACKGROUNDOncogenes are commonly amplified on extrachromosomal DNA (ecDNA) contributing to poor outcomes for patients. Currently, the chronology of ecDNA development is not known. We studied the origination and evolution of ecDNA in patients with Barretts esophagus (BE) who progressed to esophageal adenocarcinoma (EAC). METHODSWe analyzed whole-genome sequencing (WGS) data from a BE surveillance cohort and EAC patients at Cambridge University UK (n=206 patients). We also analyzed WGS data from biopsies taken at two time points from multiple sites in the esophagus from 80 patients enrolled in a case-control study at the Fred Hutchinson Cancer Center (FHCC) - 40 BE patients who progressed to EAC and 40 who did not. RESULTSecDNA was detected in 24% and 43% of BE patients with BE-associated early and late-stage EAC, respectively, in the Cambridge cross-sectional cohort. ecDNA was found in 33% of all FHCC BE patients who developed cancer, either prior to, or at EAC diagnosis. ecDNA was strongly associated with patients who developed cancer, in contrast with FHCC BE patients who did not progress (odds ratio, 18.8, CI - 2.3-152, p=3.3x10-4). ecDNAs were enriched for oncogenes and immunomodulatory genes and could be detected early in the transition from high-grade dysplasia to cancer and increased in copy number and complexity over time. CONCLUSIONSecDNAs can develop before a diagnosis of cancer in BE patients and are strongly selected for during the evolution to EAC. ecDNAs promote diverse oncogene and immunomodulatory gene amplification during EAC development and progression.

genomics↗

bioRxiv2021

Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment

Not all cancer patients with severe neutropenia develop fever, and the fecal microbiome may play a role. In neutropenic hematopoietic cell transplant patients (n=119), 63 (53%) developed a subsequent fever and had increased fecal Akkermansia muciniphila, a mucus-degrading bacteria (p=0.006, corrected for multiple comparisons). In mouse models, two therapies, irradiation and melphalan, similarly expanded A. muciniphila. Dietary restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Azithromycin treatment depleted A. muciniphila and preserved colonic mucus. Dietary restriction raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila with lower pH and increased propionate prevented utilization of mucin. Treating irradiated mice with azithromycin or propionate preserved the mucus layer, lessened hypothermia, and reduced inflammatory cytokines in the colon. These results suggest that diet, metabolites and colonic mucus link the microbiome to neutropenic fever, and could guide future microbiome-based preventive strategies.

microbiology↗

bioRxiv2019

Novel patterns of complex structural variation revealed across thousands of cancer genome graphs

Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g. deletion, translocation) or complex (e.g. chromothripsis, chromoplexy) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,833 tumor whole genome sequences (WGS), we introduce three complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early replicating regions and superenhancers, and are enriched in breast and ovarian cancers. Rigma comprise "chasms" of low-JCN deletions at late-replicating fragile sites in esophageal and other gastrointestinal (GI) adenocarcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold back inversions that are enriched in acral but not cutaneous melanoma and associated with a previously uncharacterized mutational process of non-APOBEC kataegis. Clustering of tumors according to genome graph-derived features identifies subgroups associated with DNA repair defects and poor prognosis.

genomics↗