Biology subjects

Barrodia, P.

Publications and source records attributed to Barrodia, P..

3 recordsLinked to original sources

bioRxiv2026

Fasting primes small intestinal regeneration after damage via a microbiome metabolite chromatin axis

Fasting enhances small intestinal regeneration after radiation but the contribution of the gut microbiome to this process remains uncharacterized. We identify Akkermansia muciniphila (AKK) as a key mediator of this response. AKK was enriched in fasted mice and its antibiotic depletion abrogated radioprotection whereas reintroduction restored both organismal survival and intestinal integrity. Fasting elevated propionic acid, consistent with AKKs metabolic output. AKK-conditioned medium and propionate induced histone H3 acetylation in intestinal stem cell cultures while in vivo fasting induced AKK-dependent H3K27ac and H3K9ac, remodeling promoter-enhancer landscapes in crypt epithelial cells. Epigenetic profiling revealed a rewired core regulatory program enriched for pioneer transcription factors (Foxa, Gata, Klf), architectural organizers (Ctcf, Boris), and lineage-defining and metabolic regulators (Cdx2, Hnf4). This program supports expansion of a population of persister stem cells characterized by open chromatin accessibility at key stem and regenerative-associated loci including Clu, Olfm4, Lgr5, Ascl2, Lrig1, Sox9, Rnf43, and Axin2. These findings define a fasting-induced microbiome-metabolite-chromatin axis that epigenetically primes highly plastic persister stem cells for rapid regeneration of the intestinal epithelium following radiation-induced injury. Significance StatementFasting changes the gut microbiome, but how these changes help the body recover from damage is not well understood. We found that fasting increases a helpful bacterium, Akkermansia muciniphila, which produces propionate, which drives epigenetic changes by modifying histones and regulating gene activity. These changes promote the expansion of persister stem cells that help the intestine recover after radiation. This study shows how fasting and gut bacteria work together to protect healthy tissue and suggests that diet or microbial treatments could help reduce side effects of cancer radiotherapy.

cell biology↗

bioRxiv2025

Cfap300 regulates the transdifferentiation of Corpuscle of Stannius cells in zebrafish

Stanniocalcin 1 (Stc1) is a hormone secreted by the Corpuscle of Stannius (CS) gland in teleost fish, including zebrafish, where it regulates calcium homeostasis. The CS gland forms by transdifferentiation of pronephric tubule epithelial cells at the distal early (DE) and distal late (DL) boundary. Although transdifferentiation is known in development and disease, the underlying mechanisms remain unclear. Here, we show that cfap300, a DNAAF implicated in primary ciliary dyskinesia (PCD), is essential for CS gland formation. TALEN-generated cfap300 mutants develop normally and show no nephron segmentation defects, but exhibit impaired CS development, which could be partially rescued by cfap300 mRNA injection. Further, cfap300 mutants display increased expression of cdh17 driven by Hnf1ba, which blocks CS precursor transdifferentiation. Knockdown of cdh17 or hnf1ba restores CS formation. These results uncover a Cfap300-Hnf1ba-Cdh17 pathway that regulates epithelial-to-endocrine transdifferentiation, revealing a novel, lineage-specific role for a DNAAF protein in endocrine organogenesis.

developmental biology↗

bioRxiv2021

KMT2D Loss Promotes Head and Neck Squamous Cell Carcinoma Through Enhancer Reprogramming and Modulation of Immune Microenvironment

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with 5-year survival of [~]50%. Genomic profiling studies have identified important somatic mutations in this disease which presents an opportunity for precision medicine. We demonstrate that KMT2D, a histone methyltransferase harbors somatic mutations in [~]17% of HNSCC and is associated with 2-year recurrence in TCGA data. Consistent with algorithmic prediction of bring a driver tumor-suppressor event, its loss results in larger oral tumors in immune-proficient orthotopic models. Mechanistically, we find that KMT2D knockdown or KMT2D mutation causes loss of H3K4me1-marked enhancers harboring IRF7/9 binding sites, which is known to regulate interferon signaling. Indeed, KMT2D loss in human and murine cell lines deregulated transcriptional levels of cytokine expression and impacted numerous immune signaling pathways, including interferon signaling. Consistently, Kmt2d knockdown in murine tumors exhibited decrease in IFN{gamma}-producing effector T cells and an increase in T-cells with an exhausted phenotype. Epistasis experiments showed that exogenous treatment with IFN{gamma} abrogated the increased tumor growth in Kmt2d-deficient oral tumors. Together, these results support the role of KMT2D as a tumor suppressor in HNSCC that regulates the tumor microenvironment by modulating H3K4me1-marked enhancers controlling interferon signaling.

cancer biology↗