Biology subjects

Song, J. Y.

Publications and source records attributed to Song, J. Y..

8 recordsLinked to original sources

bioRxiv2026

Who Formed All That Iron?: A Novel Antarctic Chemolithotroph Drives Iron Biomineralization

Iron mineralization has profoundly influenced Earths biogeochemical history1,2, yet the specific mechanisms underlying banded iron formation (BIF) remain unresolved3-5. Here we profile the microbiomes of Holocene sediments beneath the Larsen C Ice Shelf (LCIS), Antarctica6-8, through stratigraphic analysis of sedimentary ancient DNA combined with metagenomics. Distinct microbial phases aligned with glacial facies boundaries, with sub-ice shelf communities dominated by chemolithoautotrophs including an uncultured Thermodesulfovibrionia. This bacterium, visualized by fluorescence in situ hybridization and designated Candidatus Mariimomonas ferrooxydans (phylum Nitrospirota), emerged as a keystone taxon with high network centrality. Its genome encodes Cyc2, a fused porin-cytochrome outer membrane protein implicated in Fe(II) oxidation. Heterologous expression of Cyc2 in Escherichia coli confirmed its ability to catalyze iron oxidation, supporting iron precipitation under dark, anoxic conditions. These pristine LCIS sediments, unaltered since the last glacial maximum, provide a modern analogue for synglacial BIFs deposited during Neoproterozoic Snowball Earth events. Our findings deliver direct genomic and functional evidence for chemolithotrophic iron oxidation, challenge phototroph-centric models of BIF genesis, and highlight microbial iron cycling as a recurring force in Earths geochemical evolution. Beyond Earth, these insights inform interpretations of iron deposits on other planetary bodies.

microbiology↗

bioRxiv2025

Methylation variability and LINE-1 activation in multiple myeloma

Multiple myeloma (MM) is a type of hematological cancer that arises from uncontrolled proliferation of plasma cells. In addition to frequent genetic mutations, malignant plasma cells are characterized by alterations to the epigenome. Myeloma cells display a genome-wide loss of DNA methylation and a corresponding increase in active chromatin modifications. The dramatic epigenetic remodeling that occurs in cancer genomes is associated with loss of silencing at transposable elements, which can impact genome regulation. Through paired epigenome and transcriptome profiling of patient derived MM samples, we have found that loss of DNA methylation in MM genomes results in the formation of partially methylated domains that are variable across patients. This loss of DNA methylation coincides with the expression of hundreds of transcripts driven by LINE-1 (L1) retrotransposons that are epigenetically silenced in normal cells. MM samples can be stratified based on L1 activity with distinct gene expression signatures. The high L1 samples are characterized by a more proliferative, less differentiated state as well as inhibition of interferon and genome defense pathways. Several L1 promoters generate chimeric transcripts with adjacent oncogenes. We further find that KRAB-zinc finger proteins (KZFPs) that are responsible for the epigenetic silencing of L1s have abnormally low abundance in MM samples with high L1 activity. These results indicate that cell proliferation in MM is associated with a loss of KZFP expression and activation of L1 elements. SignificanceEpigenome and transcriptional profiling of patient-derived multiple myeloma samples reveals heterogeneous loss of DNA methylation, reduction of KZFP expression and LINE-1 activation as a clinical indicator of progression.

cancer biology↗

bioRxiv2025

DARG: a Database of Alzheimer Related Genes in Model Organisms

Alzheimer disease is affecting a significant portion of the aging population worldwide. Despite extensive research over the years, a comprehensive understanding of its underlying mechanisms and effective treatments remains elusive. Meanwhile, animal models, such as mouse, zebrafish, Drosophila, and C. elegans, have proven invaluable in studying human diseases. In response, we have developed DARG, a Database of Alzheimer disease-related genes in model organisms, designed to bridge the gap between human geneticists investigating the molecular mechanisms of the disease and the model organisms that can be used to explore the functions of disease-associated genes. DARG allows users to search and browse Alzheimer-related human genes from various resources and datasets, identify orthologs in model organisms, and access data on their gene expression and related phenotypes in Drosophila.

bioinformatics↗

bioRxiv2024

The prion-like protein Doppel: A soluble biomarker steering ovarian cancers peritoneal to circulatory dissemination

Detecting ovarian cancer (OC) early using existing biomarkers, e.g., cancer antigen 125 (CA125), is challenging due to its ubiquitous expression in many tissues. Doppel, a prion-like protein, expresses in male reproductive organ but absent in female reproductive systems and healthy tissues, but plays an important role in neoangiogenesis. Here, we have shown two platforms, soluble Doppel in sera/ascites and Doppel expressed circulating tumor cells (Dpl+CTC) in the whole blood, to detect subsets of epithelial OC (EOC). Increased level of Doppel in the sera of OC patients, in three different cohorts, confirm Doppel as OC specific biomarker. Serum Doppel level distinguishes EOC subtypes and early stages HGSOCs from non-cancerous conditions with high sensitivity and specificity. Stratifying the EOCs based on Doppel level, we categorized them into Doppel-high (Dplhi) and Doppel-low (Dpllow) groups. Using ascites-derived organoids and single cell sequencing of whole ascites of Dplhi and Dpllow patients, we identify that Doppel induces epithelial-mesenchymal transition (EMT) and creates an immunosuppressive microenvironment, respectively. Doppel levels in the sera/ascites correlate with the changes of Dpl+CTC number in whole blood, highlighting the association of Doppel-induced EMT with CTC dissemination in circulation. Thus, Doppel-based detection of EOC subtypes could be a promising platform as clinical biomarker and link Doppel-axis with OC dissemination.

cancer biology↗

bioRxiv2024

B cell receptor silencing reveals the origin of high-grade B cell lymphomas with MYC and BCL2 rearrangements

The B cell receptor (BCR) is essential for mature B cell lymphomas, serving as therapeutic target. Here, we show that high-grade B cell lymphomas with MYC and BCL2 rearrangements (HGBCL-DH-BCL2) predominantly exhibit immunoglobulin heavy (IGH) chain silencing, leading to BCR shutdown. HGBCL-DH-BCL2 with undetectable IGH (IGHUND) differ from IGH-expressing counterparts for germinal center-zone gene programs, MYC expression and T cell infiltration. While IGH+ HGBCL-DH-BCL2 prefer IGM/IG-Kappa expression, IGHUND counterparts have completed IGH class-switching, favoring IG-Lambda (IGL) light chains. IGHUND HGBCL-DH-BCL2 preserve IGHV gene integrity, overcoming antigen-driven selection. IGH silencing precedes onset and shapes evolution of HGBCL-DH-BCL2 from Follicular Lymphoma (FL) or FL/HGBCL-DH-BCL2 common precursor. In FL/HGBCL-DH-BCL2 pairs and HGBCL-DH-BCL2 models, BCR silencing promoted RAG1/2-dependent IG light chain editing, causing t(8;22)(q24;q11)/IGL::MYC. IGH silencing protected HGBCL-DH-BCL2 models from killing by CD79B-targeting Polatuzumab-Vedotin. Collectively, HGBCL-DH-BCL2 primarily originate from BCR-silenced isotype-switched t(14;18)/IGH::BCL2-positive (pre)FL cells acquiring IGL::MYC translocations during IG light chain revision, with clinical implications. SignificanceThese findings link BCR silencing in isotype-switched t(14;18)+ Follicular Lymphoma cells (or their precursors) to RAG1/2 re-expression, promoting IGL::MYC translocations responsible for transformation into high-grade B cell lymphomas (HGBCL). Predominant silencing of the BCR complex in HGBCL with MYC and BCL2 rearrangements protects tumor cells from CD79B-directed Polatuzumab-Vedotin killing.

cancer biology↗

bioRxiv2022

HOXD13 is a direct EWS-FLI1 target and moderates fusion-dependent transcriptional states

Oncogenic fusion proteins display exquisite tissue specificity, revealing that malignant transformation requires cooperation with cell-autonomous factors. Recent studies have also demonstrated that tumorigenicity of Ewing sarcoma requires precise regulation of the transcriptional activity of the EWS-FLI1 oncogenic driver. Here we show that the developmentally and anatomically restricted transcription factor HOXD13 is a direct target of EWS-FLI1. Transcriptomic and CUT&RUN studies revealed that HOXD13 binds active, fusion-bound enhancers, resulting in altered expression of EWS-FLI1-induced targets. More strikingly, HOXD13 was found to bind and activate cis-regulatory regions of genes that are normally repressed by EWS-FLI1. Single-cell sequencing demonstrated marked intra-tumoral heterogeneity of HOXD13 transcriptional activity and revealed that antagonism between HOXD13-mediated gene activation and EWS-FLI1-dependent gene repression confers a spectrum of transcriptional cell states along a mesenchymal axis. Thus, HOXD13 serves as an internal rheostat for EWS-FLI1 activity, providing a paradigm for tissue-specific transcription factors as critical partners in fusion-driven cancers.

cancer biology↗

bioRxiv2021

Longitudinal preclinical imaging characterization of drug delivery potential after radiotherapy in the healthy and leukemic bone marrow vascular microenvironment

ObjectivesRadiotherapy improves blood perfusion and cellular chemotherapy uptake in mice with acute lymphoblastic leukemia (ALL). However, its ability to influence drug delivery and permeation through the bone marrow vasculature (BMV) is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton (L-QMPM) imaging and used it to characterize drug delivery potential and the BMV before and after radiotherapy in mice bearing leukemia. MethodsWe developed a longitudinal window implant for L-QMPM imaging of the calvarium BMV before, 2 days after, and 5 days after radiotherapy. Live time-lapsed images of a fluorescent drug surrogate were used to obtain measurements including tissue wash-in slope (WIStissue) to measure drug delivery potential. We performed L-QMPM imaging using 2 Gy and 10 Gy total body irradiation (TBI) on C57/B6 (WT) mice, mice bearing ALL, and acute myeloid leukemia (AML). ResultsImplants had no effects on calvarium dose, and parameters for WT untreated mice were stable during imaging. We observed increased angiogenesis, decreased single-vessel blood flow, and decreased WIStissue with the onset of AML and ALL. 2Gy and 10Gy TBI increased WIStissue 2 days after radiotherapy in all 3 groups of mice and increased single-vessel blood flow in mice bearing ALL and AML. Significant increases in WIStissue were observed 2 days after 2Gy TBI compared to 5 days. Morphological and functional alterations in the BMV were sustained for a significantly longer time period after 10Gy TBI (5 days post-treatment) compared to 2Gy TBI (2 days post-treatment). ConclusionL-QMPM provides stable functional assessments of the BMV. TBI increases the drug delivery potential of the leukemic BMV 2-5 days post-treatment, likely through improved blood perfusion and drug exchange from the BMV to the extravascular tissue. Our data show that neo-adjuvant 2Gy and 10Gy TBI condition the BMV for increased drug delivery.

cancer biology↗

bioRxiv2019

Antigen-Specific Immune Decoys Intercept and Exhaust Autoimmunity to Prevent Disease

Relapsing-remitting patterns of many autoimmune diseases such as multiple sclerosis (MS) are perpetuated by a recurring circuit of adaptive immune cells that amplify in secondary lymphoid organs (SLOs) and traffic to compartments where antigen is abundant to elicit damage. Some of the most effective immunotherapies impede the migration of immune cells through this circuit, however, broadly suppressing immune cell migration can introduce life-threatening risks for patients. We developed antigen-specific immune decoys (ASIDs) to mimic tissues targeted in autoimmunity and selectively intercept autoimmune cells to preserve host tissue. Using Experimental Autoimmune Encephalomyelitis (EAE) as a model, we conjugated autoantigen PLP139-151 to a microporous collagen scaffold. By subcutaneously implanting ASIDs after induction but prior to the onset of symptoms, mice were protected from paralysis. ASID implants were rich with autoimmune cells, however, reactivity to cognate antigen was substantially diminished and apoptosis was prevalent. ASID-implanted mice consistently exhibited engorged spleens when disease normally peaked. In addition, splenocyte antigen-presenting cells were highly activated in response to PLP rechallenge, but CD3+ and CD19+ effector subsets were significantly decreased, suggesting exhaustion. ASID-implanted mice never developed EAE relapse symptoms even though the ASID material had long since degraded, suggesting exhausted autoimmune cells did not recover functionality. Together, data suggested ASIDs were able to sequester and exhaust immune cells in an antigen-specific fashion, thus offering a compelling approach to inhibit the migration circuit underlying autoimmunity.

bioengineering↗