Biology subjects

Dodson, C.

Publications and source records attributed to Dodson, C..

5 recordsLinked to original sources

bioRxiv2026

BMP6 coordinates dermal papilla and epithelial cell states for hair follicle engineering and regeneration

Human hair follicle engineering is hindered by the rapid loss of inductive competence in culture-expanded dermal papilla (DP) fibroblasts. Here we show that bone morphogenetic protein 6 (BMP6) maintains and restores DP-associated characteristics while promoting follicular epithelial differentiation by restricting keratinocyte (KC) proliferation and inducing hair follicle-associated marker expression. Human follicle transcriptomics further linked BMP activity to DP identity and follicular epithelial differentiation. Genetic mouse studies demonstrate that BMP6 in Sox2-positive DP cells contributes to normal anagen onset, progression, and maintenance. Gain- and loss-of-function studies in KC-DP organoids show that BMP6 promotes epithelial-mesenchymal organization and spatially patterned follicular structures. In vivo, topical BMP6 promotes anagen onset, whereas BMP6 overexpression restores the hair follicle-generating capacity of late-passage human DP fibroblasts. Together, these findings identify BMP6 as a compartment-dependent regulator that enhances human DP competence and promotes epithelial differentiation, supporting regenerative hair follicle formation and engineering with culture-expanded DP cells.

developmental biology↗

bioRxiv2025

Multi-omics identification of activated T cells and spatial PD-1/PD-L1 signaling as biomarkers of diabetic foot ulcer healing

Diabetic foot ulcers (DFUs) are a common and debilitating complication of diabetes, and amputations from non-healing ulcers carry high morbidity and mortality. A critical need exists for biomarkers that can identify healing potential early and guide targeted interventions. To address this, we applied an integrated multi-omics approach across four patient cohorts comprising 51 DFUs (29 Healing, 22 Non-healing). Bulk RNA-sequencing revealed marked activation of Th1 and Th2 pathways (activation z-score +4.8, p = 3.8x10-{superscript 1}), and immune cell deconvolution predicted higher proportions of T cell populations in Healers. Spatial proteomics in a second cohort identified elevated CD3 T cell density and selective enrichment of PD-1 and PD-L1 expression in vascular niches of the papillary dermis in Healers (p < 0.001). Flow cytometry in a third cohort further demonstrated higher proportions of CD3PD-1 and CD3PD-L1 T cells in Healers compared with Non-healers. Single-cell RNA-sequencing from a fourth cohort showed upregulation of PD-1 and PD-L1 within CD4 T cells from Healers. Complementary immunofluorescence and serological profiling confirmed that both PD-1 and PD-L1 are elevated in tissue and circulating serum of healing DFUs, supporting their potential use as systemic biomarkers. Taken together, vascular-enriched PD-1/PD-L1 signaling and T cell activation were observed in association with healing DFUs, supporting PD-1/PD-L1 as candidate biomarkers in both tissue and blood with potential translational relevance for predicting DFU outcomes and informing precision therapies.

immunology↗

bioRxiv2025

A human ex vivo model of radiation-induced skin injury reveals p53-driven DNA damage signaling and recapitulates a TGFβ fibrotic response

Radiation-induced skin injury is a poorly understood complication affecting cancer patients who undergo radiotherapy, with no current therapies able to prevent or halt its progression to debilitating radiation-induced skin fibrosis (RISF). Addressing the need for clinically relevant human models, this study developed and characterized a human ex vivo skin model that recapitulates the temporal molecular processes of cutaneous radiation injury, as demonstrated through bulk RNA-sequencing and tissue validation studies. Human skin explants subjected to ionizing radiation demonstrated rapid induction of DNA double-strand breaks, followed by a robust, p53-driven transcriptional program involving genes related to cell cycle arrest, apoptosis, and senescence. Over time, the irradiated skin exhibited increasing activation of pro-fibrotic pathways, notably epithelial-mesenchymal transition and TGF{beta}1-mediated signaling. This resulted in upregulation of classic fibrosis markers such as COL1A1, FN1, and increased collagen thickness. Importantly, regulators of the p53 axis, MDM2 and miR-34a, was observed, implicating these factors as potential therapeutic targets to modulate the balance between repair of radiation injury and pathologic fibrosis. Transcriptome analysis of irradiated and non-irradiated breast skin from post-mastectomy patients showed notable concordance of p53 and pro-fibrotic gene signatures comparable to the ex vivo model, underscoring its translational relevance. This work provides a platform for identifying early biomarkers and testing therapeutic strategies to prevent or mitigate cutaneous radiation toxicities, including RISF, beginning with elucidating the dynamic interplay between the p53-mediated DNA damage response and the onset of fibrosis following radiation. Ultimately, this work aims to improve long-term skin health and quality of life for cancer patients. One Sentence SummaryHuman ex vivo skin recapitulates a clinically relevant p53-mediated DNA damage and pro-fibrotic response to radiation.

genomics↗

bioRxiv2022

Additive genetic effects in interacting species jointly determine the outcome of caterpillar herbivory

Plant-insect interactions are common and important in basic and applied biology. Trait and genetic variation can affect the outcome and evolution of these interactions, but the relative contributions of plant and insect genetic variation and how these interact remain unclear and are rarely subject to assessment in the same experimental context. Here we address this knowledge gap using a recent host range expansion onto alfalfa by the Melissa blue butterfly. Common garden rearing experiments and genomic data show that caterpillar performance depends on plant and insect genetic variation, with insect genetics contributing to performance earlier in development and plant genetics later. Our models of performance based on caterpillar genetics retained predictive power when applied to a second common garden. Much of the plant genetic effect could be explained by heritable variation in plant phytochemicals, especially saponins, peptides, and phosphatidyl cholines, providing a mechanistic understanding of variation in the species interaction. We find evidence of polygenic, mostly additive effects within and between species, with consistent effects of plant genotype on growth and development across multiple butterfly species. Our results inform theories of plant-insect coevolution and the evolution of diet breadth in herbivorous insects and other host-specific parasites. Teaser summaryThe combined, additive effects of plant and insect genetic variation explain Melissa blue caterpillar growth and development on alfalfa plants.

genomics↗

bioRxiv2020

Leveraging biological complexity to predict patch occupancy in a recent host range expansion

Specialized plant-insect interactions are a defining feature of life on earth, yet we are only beginning to understand the factors that set limits on host ranges in herbivorous insects. To understand the colonization of alfalfa by the Melissa blue butterfly, we quantified arthropod assemblages and plant metabolites across a wide geographic region, while controlling for climate and dispersal inferred from population genomic variation. The presence of the butterfly is successfully predicted by direct and indirect effects of plant traits and interactions with other species. Results are consistent with the predictions of a theoretical model of parasite host range in which specialization is an epiphenomenon of the many barriers to be overcome rather than a consequence of trade-offs in developmental physiology. One sentence summaryThe formation of a novel plant-insect interaction can be predicted with a combination of biotic and abiotic factors, with comparable importance revealed for metabolomic variation in plants and interactions with mutualists, competitors and enemies.

ecology↗