Biology subjects

Murphy, B. A.

Publications and source records attributed to Murphy, B. A..

5 recordsLinked to original sources

bioRxiv2025

An integrated single-cell and spatial transcriptomic atlas of thyroid cancer progression identifies prognostic fibroblast subpopulations

Thyroid cancer progression from curable well-differentiated thyroid carcinoma to highly lethal anaplastic thyroid carcinoma is distinguished by tumor cell de-differentiation and recruitment of a robust stromal infiltrate. Combining an integrated thyroid cancer single-cell sequencing atlas with spatial transcriptomics and bulk RNA-sequencing, we define stromal cell subpopulations and tumor-stromal cross-talk occurring across the histologic and mutational spectrum of thyroid cancer. We identify distinct inflammatory and myofibroblastic cancer-associated fibroblast (iCAF and myCAF) populations and perivascular-like populations. The myCAF population is only found in malignant samples and is associated with tumor cell invasion, BRAFV600E mutation, lymph node metastasis, and disease progression. Tumor-adjacent myCAFs abut invasive tumor cells with a partial epithelial-to-mesenchymal phenotype. Tumor-distant iCAFs infiltrate inflammatory autoimmune thyroid lesions and anaplastic tumors. In summary, our study provides an integrated atlas of thyroid cancer fibroblast subtypes and spatial characterization at sites of tumor invasion and de-differentiation, defining the stromal reorganization central to disease progression.

cancer biology↗

bioRxiv2024

Tenascin-C potentiates Wnt signaling in thyroid cancer

Tenascin-C (TNC) is a secreted extracellular matrix protein that is highly expressed during embryonic development and re-expressed during wound healing, inflammation, and neoplasia. Studies in developmental models suggest that TNC may regulate the Wnt signaling pathway. Our lab has shown high levels of Wnt signaling and TNC expression in anaplastic thyroid cancer (ATC), a highly lethal cancer with an abysmal [~]3-5 month median survival. Here, we investigated the role of TNC in facilitating ligand-dependent Wnt signaling in thyroid cancer. We utilized bulk RNA-sequencing from three independent multi-institutional thyroid cancer patient cohorts. TNC expression was spatially localized in patient tumors with RNA in situ hybridization. The role of TNC was investigated in vitro using Wnt reporter assays and in vivo with a NOD.PrkdcscidIl2rg-/- mouse ATC xenograft tumor model. TNC expression was associated with aggressive thyroid cancer behavior, including anaplastic histology, extrathyroidal extension, and metastasis. Spatial localization of TNC in patient tissue demonstrated a dramatic increase in expression within cancer cells along the invasive edge, adjacent to Wnt ligand-producing fibroblasts. TNC expression was also increased in areas of intravascular invasion. In vitro, TNC bound Wnt ligands and potentiated Wnt signaling. Finally, in an ATC mouse model, TNC increased Wnt signaling, tumor burden, invasion, and metastasis. Altogether, TNC potentiated ligand driven Wnt signaling and promotes cancer cell invasion and metastasis in a mouse model of thyroid cancer. Understanding the role of TNC and its interaction with Wnt ligands could lead to the development of novel biomarkers and targeted therapeutics for thyroid cancer.

cancer biology↗

bioRxiv2022

Long-read RNA Sequencing Improves the Annotation of the Equine Transcriptome

1A high-quality reference genome assembly, a biobank of diverse equine tissues from the Functional Annotation of the Animal Genome (FAANG) initiative, and incorporation of long-read sequencing technologies, have enabled efforts to build a comprehensive and tissue-specific equine transcriptome. The equine FAANG transcriptome reported here provides up to 45% improvement in transcriptome completeness across tissue types when compared to either RefSeq or Ensembl transcriptomes. This transcriptome also provides major improvements in the identification of alternatively spliced isoforms, novel noncoding genes, and 3 transcription termination site (TTS) annotations. The equine FAANG transcriptome will empower future functional studies of important equine traits while providing future opportunities to identify allele-specific expression and differentially expressed genes across tissues.

genomics↗

bioRxiv2021

Effects of blue monochromatic light directed at one eye of pregnant horse mares on gestation, parturition and foal maturity

Blue light directed at one eye advances the equine ovulatory season but can also advance foaling. In this study, effects of blue LED light on pregnancy outcome were assessed. Twenty mares with singleton pregnancies were studied over two consecutive years in a cross-over design. In one year, mares received an extended photoperiod using 50 lux of blue LED light (468 nm) directed at a single eye from 08:00 until 23:00 daily via head-worn light masks starting mid-December and in the other year remained untreated as controls. Gestation was shorter in blue LED light-treated (333.2{+/-}1.0 days,{+/-}SEM) than in control pregnancies (337.9{+/-}1.8 days, p<0.05). Colostral IgG content was lower in treated than in control pregnancies (p<0.05) but was adequate to ensure sufficient IgG transfer to newborn foals with a single exception. Foals born to blue LED light-treated mares had lower wither heights (102.5{+/-}1.1 vs. 105.2{+/-}1.0 cm, p<0.01), similar weights (55.0{+/-}1.3 vs. 55.5{+/-}1.1 kg) and took less time to stand after birth than control foals (39{+/-}3 vs. 56{+/-}4 min, p<0.05). The neutrophil/lymphocyte ratio, was higher in foals born to blue LED light-treated mares than controls (3.2{+/-}0.2 vs. 2.7{+/-}0.2; p<0.05). Foals born to blue LED light-treated mares had reduced hair length compared to controls (13.1{+/-}0.8 vs. 20.9{+/-}0.1 mm; p<0.001) and hair regrowth in treated mares was reduced (p<0.05). Maternal plasma prolactin concentration was increased in treated mares (p=0.05) and peaked at foaling (p<0.001). In conclusion, blue LED light directed at one eye advanced foaling and influenced height, hair coat and maturity in foals.

physiology↗

bioRxiv2018

Neural ensemble dynamics in dorsal motor cortex during speech in people with paralysis

Speaking is a sensorimotor behavior whose neural basis is difficult to study at the resolution of single neurons due to the scarcity of human intracortical measurements and the lack of animal models. We recorded from electrode arrays in the hand knob area of motor cortex in people with tetraplegia. Neurons in this area, which have not previously been implicated in speech, modulated during speaking and during non-speaking movement of the tongue, lips, and jaw. This challenges whether the conventional model of a motor homunculus division by major body regions extends to the single-neuron scale. Spoken words and syllables could be decoded from single trials, demonstrating the potential utility of intracortical recordings for brain-computer interfaces (BCIs) to restore speech. Two neural population dynamics features previously reported for arm movements were also present during speaking: a large initial condition-invariant signal, followed by rotatory dynamics. This suggests that common neural dynamical motifs may underlie movement of arm and speech articulators.

neuroscience↗