Biology subjects

Skaggs, T.

Publications and source records attributed to Skaggs, T..

3 recordsLinked to original sources

bioRxiv2026

β-Hydroxybutyrate elicits divergent metabolic responses between MCF-7 and T47D ER+ breast cancer cells under glucose restriction

BackgroundThe ketogenic diet is being explored as an adjuvant intervention in breast cancer because it lowers circulating glucose and elevates ketone bodies such as {beta}-hydroxybutyrate (BHB), but how individual ER+ breast cancer subtypes adapt to these conditions remains poorly characterized. We examined metabolic responses to BHB supplementation under glucose restriction in two ER+ breast cancer cell lines, asking whether metabolic adaptation patterns differ between models. MethodsMCF-7 and T47D cells were cultured under high glucose, glucose-restricted (5% of standard), or glucose-restricted with 10 mM BHB conditions and profiled by comprehensive two-dimensional gas chromatography-mass spectrometry (GCxGC-MS). Pairwise Welchs t-tests with Benjamini-Hochberg false discovery rate (FDR) correction were applied to identify treatment-responsive metabolites. Targeted assays quantified intracellular glycine, SHMT1 protein, and total branched-chain amino acid (BCAA) concentrations across a BHB dose range (2.5-15 mM). Patient tumor transcriptomic data from TCGA (n=1,084) and paired tumor-normal samples from GSE58135 (n=20) were analyzed for genes involved in one-carbon, ketone body, and BCAA metabolism. ResultsMCF-7 and T47D cells exhibited markedly divergent metabolic responses to BHB. In MCF-7 cells, BHB supplementation produced a broad pattern-level metabolic shift: 75% of detected metabolites trended upward when BHB was added to glucose-restricted cultures (C vs. B comparison), with 1,4-butanediol reaching nominal significance (FC=2.35, p=0.016) and a 4.1-fold trend increase in lactic acid (p=0.11), although no individual metabolite survived FDR correction. T47D cells showed essentially no metabolic response to BHB at the global level. Targeted assays detected an elevation in glycine at 5 mM BHB in both cell lines that did not follow a monotonic dose response and was not accompanied by changes in SHMT1 protein expression. Total BCAA levels were elevated by BHB in T47D cells but remained unchanged in MCF-7 cells. In paired patient samples, OXCT1 (log2FC = -1.41), SHMT1 (log2FC = -1.31), and ACAT1 (log2FC = -1.07) were significantly downregulated in ER+ tumors relative to matched normal tissue (adjusted p < 0.001 for all three). ConclusionsER+ breast cancer cell lines show heterogeneous metabolic responses to BHB supplementation under glucose restriction. The broad pattern of metabolite elevation in MCF-7 but not T47D cells suggests that capacity to utilize ketone bodies as metabolic substrate varies between ER+ models. The downregulation of OXCT1, ACAT1, and SHMT1 in ER+ tumors compared to normal tissue identifies these enzymes as candidate biomarkers that may help stratify which patients are likely to benefit from ketogenic interventions. Findings related to individual metabolites should be regarded as exploratory and require validation in larger, adequately powered cohorts.

cancer biology↗

bioRxiv2022

Like mother, like daughter? Phenotypic plasticity, environmental covariation, and heritability of size in a parthenogenetic wasp

Dinocampus coccinellae (Hymenoptera:Braconidae, Euphorinae) is a solitary, generalist Braconid parasitoid wasp that reproduces through thelytokous parthenogenesis, an asexual process in which diploid daughters emerge from unfertilized eggs, and parasitizes over fifty diverse species of coccinellid ladybeetles worldwide as hosts. Here we utilized a common garden and reciprocal transplant experiment using parthenogenetic lines of D. coccinellae presented with three different host ladybeetle species of varying sizes, across multiple generations to investigate heritability, plasticity, and environmental covariation of body size in D. coccinellae. We expected positively correlated parent-offspring parasitoid regressions, indicative of heritable size variation, from unilineal (parent and offspring reared on same host species) lines, since these restrict environmental variation in phenotypes. In contrast, because multilineal (parent and offspring reared on different host species) lines would induce phenotypic plasticity of clones reared in varying environments, we expected negatively correlated parent-offspring parasitoid regressions. Our results indicate (1) little heritable variation in body size, (2) strong independence of offspring size on the host environment, (3) a consistent signal of size-host tradeoff wherein small mothers produced larger offspring, and vice versa, independent of host environment. We then model the evolution of size and host-shifting under a constrained fecundity advantage model of Copes Law using a Hidden Markov Model, showing that D. coccinellae likely has considerable fitness advantage to maintain phenotypic plasticity in body size despite parthenogenetic reproduction.

evolutionary biology↗

bioRxiv2021

Genome of the parasitoid wasp Dinocampus coccinellae reveals extensive duplications, accelerated evolution, and independent origins of thelytokous parthenogeny and solitary behavior

Dinocampus coccinellae (Hymenoptera: Braconidae) is a generalist parasitoid wasp that parasitizes >50 species of predatory lady beetles (Coleoptera: Coccinellidae), with thelytokous parthenogeny as its primary mode of reproduction. Here we present the first high quality genome of D. coccinellae using a combination of short and long read sequencing technologies, followed by assembly and scaffolding of chromosomal segments using Chicago+ HiC technologies. We also present a first-pass ab initio genome annotation, and resolve timings of divergence and evolution of (1) solitary behavior vs eusociality, (2) arrhenotokous vs thelytokous parthenogenesis, and (3) rates of gene loss and gain among Hymenopteran lineages. Our study finds (1) at least two independent origins of eusociality and solitary behavior among Hymenoptera, (2) two independent origins of thelytokous parthenogenesis from ancestral arrhenotoky, and (3) accelerated rates of gene duplications, loss, and gain along the lineages leading to D. coccinellae. Our work both affirms the ancient divergence of Braconid wasps from ancestral Hymenopterans and accelerated rates of evolution in response to adaptations to novel hosts, including polyDNA viral co-evolution.

genomics↗