Biology subjects

Rupp, S. M.

Publications and source records attributed to Rupp, S. M..

6 recordsLinked to original sources

bioRxiv2025

Immune-cancer analyses across mammals reveal a potential trophic level and platelet-linked tradeoff between cancer and trauma mortality

There may be fitness tradeoffs between wound healing, immune responses, and cancer development due to shared pathways, limited resources and conflicting selective pressures. The immune system is important in both response to injury and carcinogenesis. We initially investigated correlations between cancer prevalence and immune cells, controlling for known associations with body mass and lifespan. We analyzed data from 216 mammalian species from at least 20 individuals per species. Body mass correlated positively with segmented neutrophil-to-lymphocyte ratios and negatively with lymphocyte concentrations. However, only platelet concentration correlated (negatively) with cancer prevalence (P-value = 0.006). To further understand this association, we investigated whether a fitness tradeoff could exist between preventing death from cancer versus injury. We discovered a negative correlation between cancer and trauma mortalities (P-value [≤] 0.0006), even when we accounted for the fact that different causes of death must sum to 100%. Platelet size and trophic level negatively correlated with trauma mortality, but not when controlling for cancer mortality (P-value = 0.06). If trauma mortality is an indirect measure of wound healing, this suggests a fitness tradeoff may exist between cancer suppression and wound healing across mammals, mediated in part through platelet size and trophic level.

evolutionary biology↗

bioRxiv2023

The relationship between diet, plasma glucose, and cancer prevalence across vertebrates

Could diet and mean plasma glucose concentration (MPGluC) explain the variation in cancer prevalence across species? We collected diet, MPGluC, and neoplasia data for 160 vertebrate species from existing databases. We found that MPGluC negatively correlates with cancer and neoplasia prevalence, mostly of gastrointestinal organs. Trophic level positively correlates with cancer and neoplasia prevalence even after controlling for species MPGluC. Most species with high MPGluC (50/78 species = 64.1%) were birds. Most species in high trophic levels (42/53 species = 79.2%) were reptiles and mammals. Our results may be explained by the evolution of insulin resistance in birds which selected for loss or downregulation of genes related to insulin-mediated glucose import in cells. This led to higher MPGluC, intracellular caloric restriction, production of fewer reactive oxygen species and inflammatory cytokines, and longer telomeres contributing to longer longevity and lower neoplasia prevalence in extant birds relative to other vertebrates.

cancer biology↗

bioRxiv2023

Life history and cancer in birds: clutch size predicts cancer

Cancer is a disease that affects nearly all multicellular life, including birds. However, little is known about what factors explain the variance in cancer prevalence among species. Litter size is positively correlated with cancer prevalence in managed species of mammals, and larger body size, but not incubation or nestling period, is linked to tumor prevalence in wild birds. Also, birds that produce more elaborate sexual traits are expected to have fewer resources for cancer defenses and thus higher cancer prevalence. In this study, we examined whether cancer prevalence is associated with a wide variety of life history traits (clutch size, incubation length, body mass, lifespan, and the extent of sexual dimorphism) across 108 species of managed birds in 25 different zoological facilities, sanctuaries, and veterinary clinics. We found that clutch size was positively correlated with cancer and neoplasia (both benign and malignant) prevalence, even after controlling for body mass. Cancer prevalence was not associated with incubation length, body mass, lifespan, or sexual dimorphism. The positive correlations of clutch size with cancer prevalence and neoplasia prevalence suggest that there may be life-history trade-offs between reproductive investment and somatic maintenance (in the form of cancer prevention mechanisms) in managed birds.

cancer biology↗

bioRxiv2022

The ecology of cancer prevalence across species: Cancer prevalence is highest in desert species and high trophic levels

The ecology in which species live and evolve likely affects their health and vulnerability to diseases including cancer. Using 14,267 necropsy records across 244 vertebrate species, we tested if animals in low productivity habitats, with large habitat range, high body temperature and weight-inferred estimates of metabolic rates, and in high trophic levels (from lowest to highest: herbivores, invertivores, primary carnivores, and secondary carnivores) are linked with having increased prevalence of neoplasia. This study found that: (1) habitat productivity negatively correlated with the prevalence of malignancy and neoplasia across tissues, and malignancy and neoplasia in gastrointestinal tissues; (2) inferred metabolic rates negatively correlated with the prevalence of neoplasia; and (3) trophic levels positively correlated with malignancy and neoplasia prevalence in both mammals and non-mammals. However, only the correlations with trophic levels remained significant after Bonferroni corrections for multiple testing. There are several mechanisms that might explain these findings, including the biomagnification of carcinogens in higher trophic levels, as well as tradeoffs between cancer suppression versus reproduction and survival in low productivity environments.

cancer biology↗

bioRxiv2020

A new method to accurately identify single nucleotide variants using small FFPE breast samples.

Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however, it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic algorithm to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing algorithms. We found that the SNV-identification accuracy declined when there was less than 40ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ (DCIS) of the breast to their adjacent invasive ductal carcinoma (IDC) samples. We observed an increased number of mutations (paired-samples sign test, p<0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, p<0.01). Our algorithm provides a significant improvement in detecting SNVs in FFPE samples over previous approaches. Key PointsO_LIThe sequencing of reduced quantities of DNA extracted from FFPE samples leads to substantial sequencing errors that require correction in order to obtain accurate detection of somatic mutations. C_LIO_LIWe developed and validated a new bioinformatic algorithm to robustly identify somatic single nucleotide variants using small amounts of DNA extracted from archival FFPE samples of breast cancers. C_LIO_LIVariant calling software packages need to be optimized to reduce the impact of sequencing errors. Our bioinformatics pipeline represents a significant methodological advance compared to the currently available bioinformatic tools used for the analysis of small FFPE samples. C_LI

genomics↗

bioRxiv2020

Elephant genomes reveal insights into differences in disease defense mechanisms between species

Disease susceptibility and resistance comprise important factors in conservation, particularly in elephants. To determine genetic mechanisms underlying disease resistance and other unique elephant traits, we estimated 862 and 1,017 potential regulatory elements in Asian and African elephants, respectively. These elements are significantly enriched in both species with differentially expressed genes involved in immunity pathways, including tumor-necrosis factor which plays a role in the response to elephant endotheliotropic herpesvirus (EEHV). Population genomics analyses indicate that amplified TP53 retrogenes are maintained by purifying selection and may contribute to cancer resistance in elephants, including less malignancies in African vs. Asian elephants. Positive selection scans across elephant genomes revealed genes that may control iconic elephant traits such as tusk development, memory, and somatic maintenance. Our study supports the hypothesis that interspecies variation in gene regulation contributes to differential inflammatory responses leading to increased infectious disease and cancer susceptibility in Asian versus African elephants. Genomics can inform functional immunological studies which may improve both conservation for elephants and human therapies.

evolutionary biology↗