Biology subjects

Lee, D. Y.

Publications and source records attributed to Lee, D. Y..

6 recordsLinked to original sources

bioRxiv2026

Multi-Omic and Spatial Profiling Defines Outcome-Associated Tumor States in Head and Neck Adenoid Cystic Carcinoma

Abstract Head and neck adenoid cystic carcinoma (HNACC) shows highly variable clinical behavior that histopathological features only partly predict, and prognostic biomarkers for aggressive disease at diagnosis remain limited. Here, we show by integrating bulk, single-cell, and spatial transcriptomes from 25 HNACC tumors that poor survival is marked by profound loss of myoepithelial tumor cells and expansion of luminal tumor states. Both outcome groups share a myoepithelial-like origin, but aggressive tumors converge on an actively dividing, MYC/E2F-driven luminal state concentrated in discrete spatial niches. Aggressiveness therefore reflects where tumors end along a shared developmental path rather than a distinct lineage or altered immune infiltration. A four-gene classifier capturing this state predicted survival in an independent cohort, outperforming larger signatures and flagging aggressive subgroups in two others. These findings define a lineage proliferation axis linked to HNACC outcome, providing a basis for prospective risk stratification and proliferative-directed therapy.

cancer biology↗

bioRxiv2025

Keratin degradation reflects a starvation survival strategy in Fervidobacterium islandicum AW-1

Keratin is a highly cross-linked, disulfide-rich protein that resists proteolysis, which poses a major challenge for microbial degradation. Here, we show that Fervidobacterium islandicum AW-1 initiates a starvation-induced keratinolytic program involving membrane-associated proteases and redox-mediated sulfitolysis. Multi-omics integration reveals that nutrient limitation triggers global metabolic reprogramming, promoting sulfur assimilation, biofilm formation, and chemotaxis-linked persister-like adaptation. Substrate-specific transcriptomics identified a temporally regulated protease repertoire tightly coordinated with sulfitolytic activity, facilitating efficient feather decomposition under starvation. Protein-protein interaction networks uncovered stress-responsive transcriptional regulators that govern this process. Time-resolved gene expression analysis and metabolomic profiling further revealed that cyclic-di-GMP signaling, stringent response, and flagella assembly mediate transitions between motility and sessile growth, contributing to surface colonization and persistence. Together, our findings establish a starvation-responsive survival mechanism that couples keratin degradation to stress adaptation in extreme environments, offering insights into microbial persistence and potential strategies for keratin valorization.

microbiology↗

bioRxiv2020

BET Bromodomain Proteins Regulate Transcriptional Reprogramming in Genetic Dilated Cardiomyopathy

The bromodomain and extraterminal (BET) family of epigenetic reader proteins are key regulators of pathologic gene expression in the heart. Using mice carrying a human mutation in phospholamban (PLNR9C) that develop progressive dilated cardiomyopathy (DCM), we previously identified the activation of inflammatory gene networks as a key early driver of DCM. We reasoned that BETs control this inflammatory process, representing a key node in the progression of genetic DCM. Using a chemical genetic strategy, PLNR9C or age-matched wild type mice were treated longitudinally with the BET inhibitor JQ1 or vehicle. JQ1 abrogated DCM, reduced cardiac fibrosis, and prolonged survival in PLNR9C mice by inhibiting inflammatory gene network expression at all disease stages. Cardiac fibroblast proliferation was also substantially reduced by JQ1. Interestingly, JQ1 had profound effects on pathologic gene network expression in cardiac fibroblasts, while having little effect on transcription in cardiomyocytes. Using co-immunoprecipitation, we identified BRD4 as a direct and essential regulator of NF{kappa}B-mediated inflammatory gene transcription in cardiac fibroblasts. In this this model of chronic, heritable DCM, BETs activate inflammatory gene networks in cardiac fibroblasts via an NF{kappa}B-dependent mechanism, marking them as critical effectors of pathologic gene expression.

cell biology↗

bioRxiv2019

Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

Tumor-infiltrating lymphocytes (TILs) might be associated with host-cell mediated immunity, which could be partly reflected by peripheral blood cell counts. We aimed to investigate whether peripheral blood cell counts are associated with TILs in breast cancer. Between August 2016 and July 2018, we evaluated the percentage of stromal TILs in breast cancer patients who underwent primary surgery, using the standardized methodology proposed by the international TIL Working Group. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors having high TIL levels ([≥] 50%). Peripheral blood cell counts including absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC) and neutrophil-to-lymphocyte ratio (NLR) was obtained from pretreatment laboratory data. Of the 684 patients, 99 (17.2%) had LPBC, and 478 (82.8%) had non-LBPC. In a comparison of 3 markers of peripheral blood counts, LPBC had a significantly lower mean ANC than non-LPBC (3,330 vs. 3,660; P=0.004), but the other means were not different. Decreasing ANC was an independent clinical factor in predicting LPBC (OR: 0.736, 95% CI: 0.591-0.917; P=0.004). Low peripheral ANC might be linked with LPBC, supporting the hypothesis that systemic immune cell counts might be associated with the tumor-immune microenvironment.

immunology↗

bioRxiv2019

A simple and effective sampler to collect undisturbed cores from tidal marshes

Core sampling is a common procedure in wetland ecology. PVC tubes are widely used to collect soil cores; however several studies fail to describe even the most typical characteristics of their sampling auger. This work aims to fill this gap and provide a simple and standardized core sampler design. A simple and inexpensive sampler is described for field use. Its main advantages are: 1) extraction of undisturbed cores; 7.6 cm diameter and up to 100 cm depth, 2) it is light-weight, sturdy and reliable, 3) it is made from widely available PVC items and 4) it requires minimal skills to assemble. The sampler is introduced in the wetland soil, by rotation, to the desired depth; the tooth-like edge can cut and penetrate through the dense root systems. The sampler is capped with an industrial-type stopper, and pulled up. The core is held in the sampler by suction - negative pressure. A plunger is then used to slowly remove the soil - core and sub - samples are collected. Alternatively, both ends of sampler could be sealed and taken to the lab. An 8 cm long sub-sample was adequate for soil physical, biogeochemical and molecular analysis. The sampler has been tested for 2 years with more than 200 cores taken from tidal wetlands in Chesapeake Bay, Virginia, USA. A negative correlation between salinity and organic matter content at 3 - 5 and 8 - 10 cm was found. For the deeper samples (48 - 50 cm), a positive correlation between salinity and organic matter was observed. The sampler worked satisfactory and it required no maintenance besides cleaning.

ecology↗

bioRxiv2018

MEST induces epithelial-mesenchymal transition through IL-6/JAK/STAT3 signaling in breast cancers

The loss of imprinting of MEST has been linked to certain types of cancer by promoter switching. However, MEST-mediated regulation of tumorigenicity and metastasis are yet to be understood. Herein, we reported that MEST is a key regulator of IL-6/JAK/STAT3/Twist-1 signal pathway-mediated tumor metastasis. Enhanced MEST expression is significantly associated with pathogenesis of breast cancer patients. Also, MEST induces metastatic potential of breast cancer through induction of the EMT-TFs-mediated EMT program. Moreover, MEST leads to Twist-1 induction by STAT3 activation and subsequently enables the induction of activation of the EMT program via the induction of STAT3 nuclear translocation. Furthermore, the c-terminal region of MEST was essential for STAT3 activation via the induction of JAK2/STAT3 complex formation. Finally, MEST significantly increases the breast cancers ability to metastasize from the mammary gland to the lung. These observations suggest that MEST is a promising target for intervention to prevent tumor metastasis.

cancer biology↗