Biology subjects

Hughey, J.

Publications and source records attributed to Hughey, J..

3 recordsLinked to original sources

bioRxiv2018

Population level rhythms in human skin: implications for circadian medicine

Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. Like other tissues, skin is subject to temporal fluctuations in physiological responses under both homeostatic and stressed states. To gain insight into these fluctuations, we investigated the role of the circadian clock in the transcriptional regulation of epidermis using a hybrid experimental design, where a limited set of human subjects (n=20) were sampled throughout the 24 h cycle and a larger population (n=219) were sampled once. By looking at pairwise correlations of core clock genes in 298 skin samples, we found a robust circadian oscillator in skin at the population level. Encouraged by this, we used CYCLOPS to reconstruct the temporal order of all samples and identified hundreds of rhythmically-expressed genes at the population level in human skin. We compared these results with published time-series skin data from mouse and show strong concordance in circadian phase across species for both transcripts and pathways. Further, like blood, skin is readily accessible and a potential source of biomarkers. Using ZeitZeiger, we identified a biomarker set for human skin that is capable of reporting circadian phase to within 3 h from a single sample. In summary, we show rhythms in human skin that persist at the population scale and a path to develop robust single-sample circadian biomarkers.\n\nOne Sentence SummaryHuman epidermis shows strong circadian rhythms at the population scale and provides a better source for developing robust, single-sample circadian phase biomarkers than human blood.

systems biology↗

bioRxiv2018

Two novel strains of Torulaspora delbrueckii isolated from the honey bee gut microbiome and their use in honey fermentation

Yeasts are ubiquitous microbes found in virtually all environments. Many yeast species can ferment sugar into ethanol and CO2, and humans have taken advantage of these characteristics to produce fermented beverages for thousands of years. As a naturally abundant source of fermentable sugar, honey has had a central role in such fermentations since Neolithic times. However, as beverage fermentation has become industrialized, the processes have been streamlined, including the narrow and almost exclusive usage of yeasts in the genus Saccharomyces for fermentation. We set out to identify wild honey- or honey bee-related yeasts that can be used in honey fermentation. Here, we isolated two strains of Torulaspora delbrueckii from the gut of a locally collected honey bee. Both strains were able to ferment honey sugar into mead but failed to metabolize more than a modest amount of wort sugar in trial beer fermentations. Further, the meads fermented by the T. delbrueckii strains displayed better sensory characteristics than mead fermented by a champagne yeast. The combination of T. delbrueckii and champagne yeast strains was also able to rapidly ferment honey at an industrial scale. Thus, wild yeasts represent a largely untapped reservoir for the introduction of desirable sensory characteristics in fermented beverages such as mead.

microbiology↗

bioRxiv2017

Widespread dysregulation of the circadian clock in human cancer

The mammalian circadian clock is a critical regulator of metabolism and cell division. Although multiple lines of evidence indicate that systemic disruption of the circadian clock can promote cancer, whether the clock is disrupted in primary human tumors is unknown. Here we used transcriptome data from mice to define a signature of the mammalian circadian clock based on the co-expression of 12 genes that form the core clock or are directly controlled by the clock. Our approach can be applied to samples that are not labeled with time of day and were not acquired over the entire circadian (24-h) cycle. We validated the clock signature in transcriptome data from healthy human tissues, then developed a metric we call the delta clock correlation distance ({Delta}CCD) to describe the extent to which the signature is perturbed in samples from one condition relative to another. We calculated the {Delta}CCD comparing human tumor and non-tumor samples from The Cancer Genome Atlas and eight independent datasets, discovering widespread dysregulation of clock gene co-expression in tumor samples. Subsequent analysis of data from clock gene knockouts in mice suggested that clock dysregulation in human cancer is not caused solely by loss of activity of clock genes. Furthermore, by analyzing a large set of genes previously inferred to be rhythmic in healthy human lung, we found that dysregulation of the clock in human lung cancer is accompanied by dysregulation of broader patterns of circadian co-expression. Our findings suggest that clock dysregulation is a common means by which human cancers achieve unrestrained growth and division, and that restoring clock function could be a viable therapeutic strategy in multiple cancer types. In addition, our approach opens the door to using publicly available transcriptome data to quantify clock disruption in a multitude of human phenotypes. Our method is available as a web application at https://hugheylab.shinyapps.io/deltaccd.

cancer biology↗