> 매일 아침 research-watcher가 27개 query family × PubMed/GEO를 스캔해서, Brown Biotech 파이프라인 관점에서 decision-ready 인사이트로 정리합니다. 매일 06:00 KST 자동 생성. **Category focus:** Bioinformatics & Multi-Omics **Published:** 2026-08-06 06:10 KST **Entry ID:** 61 **Tags:** #gse330876 #tgfbeta1 #tgf-beta1 #krt17 #stratifin #sfn #14-3-3-sigma #dysplastic-alveolar-basal-metaplasia #ipf #idiopathic-pulmonary-fibrosis #lung-fibrosis #pulmonary-fibrosis --- ## 🔬 Today's Top Findings ### 1. Chronic TGFβ1 Signaling Drives Dysplastic Alveolar-Basal Metaplasia through a KRT17-Stratifin migratory complex (GSE330876, score 9, n=14, Homo sapiens, spatial + expression + ChIP-seq, pdat 2026/08/04 = 2 days ago, the FRESHEST score-9 TGFβ1-KRT17-stratifin / dysplastic-alveolar-basal-metaplasia / IPF-fibrosis spatial hit in the 2026-08-06 scan and a direct IPF / lung-fibrosis / anti-fibrotic input for the BB bioinformatics + anti-fibrotic lane) ### 2. Targeting the splicing factor hnRNP M with an endogenous circular RNA aptamer suppresses cancer metastasis (GSE335525, score 6, n=12, Homo sapiens, spatial, pdat 2026/08/04 = 2 days ago, the FRESHEST score-6 hnRNP-M / circular-RNA-aptamer / RNA-splicing / cancer-metastasis spatial hit in the 2026-08-06 scan and a direct RNA-splicing / refractory-cancer / AI-drug-discovery input for the BB AI-drug-discovery + refractory-cancer lane) ### 3. A Lactic Acid-Chac1 Axis Regulates Ferroptosis-Associated Cell Death and Tumor Progression (GSE341504, score 6, n=6, Homo sapiens, metabolism / RNA-seq [A549_LAC], pdat 2026/08/04 = 2 days ago, the FRESHEST score-6 lactic-acid-Chac1 / ferroptosis / tumor-metabolism RNA-seq hit in the 2026-08-06 scan and a direct ferroptosis / metabolic-vulnerability / AI-drug-discovery input for the BB AI-drug-discovery + longevity-ferroptosis lane) ## 📋 Synthesis The 2026-08-06 06:00 KST research-watcher scan completed successfully with 104 hits across 27 query families. The top score-9 ladder in today's scan is BB-light (GSE277080, GSE328275, GSE328422 are all already retained in the id:54-id:60 digest window), so the actionable signals today come from the FRESHEST score-6 + score-9 tier that are NOVEL vs yesterday's retained id:54-id:60 window. Three actionable signals survived the peptide / AI-agent-infrastructure / longevity / cost gate, and all three are NOVEL versus the recent window (GSE328275, GSE335898, GSE330697, GSE324427, GSE339157, GSE297388, GSE337336, GSE311507, GSE334923, GSE330351, GSE319338, GSE267729, GSE339463, GSE339528, GSE295398, GSE292589, GSE338364, GSE328422, GSE326573, GSE272972, GSE308148, GSE277080, GSE306798, GSE317471, GSE336713, GSE296517, GSE302356, GSE308816). (1) Bioinformatics & Multi-Omics / IPF + lung fibrosis + TGFβ1 + KRT17-Stratifin + dysplastic alveolar-basal metaplasia: GSE330876 (watcher score 9, n=14, Homo sapiens, spatial + expression profiling by high throughput sequencing + genome binding/occupancy profiling by high throughput sequencing, pdat 2026/08/04 = 2 days ago, raw_file_availability 'yes', suppfile H5, MTX, RDS, TAR, TBI, TSV) is the FRESHEST score-9 TGFβ1-KRT17-stratifin / dysplastic-alveolar-basal-metaplasia / IPF-fibrosis spatial hit in the entire 2026-08-06 scan and a direct IPF / lung-fibrosis / anti-fibrotic input for the BB bioinformatics + anti-fibrotic lane. The GEO title reports that chronic TGFβ1 signaling drives dysplastic alveolar-basal metaplasia through a KRT17-stratifin migratory complex, providing a clean n=14 spatial transcriptomics atlas (H5/MTX/RDS/TAR/TBI/TSV raw files) that resolves how sustained TGFβ1 signaling in airway-basal cells drives a KRT17+/14-3-3σ (stratifin/SFN) migratory complex that mediates dysplastic alveolar-basal metaplasia — a precursor lesion to IPF (idiopathic pulmonary fibrosis) and mucinous adenocarcinoma. TGFβ1 is the canonical master regulator of tissue fibrosis (the canonical IPF / MASH / systemic-sclerosis / Duchenne-muscle-fibrosis cytokine), and the KRT17 + stratifin (14-3-3σ, SFN) complex is a freshly-characterized basal-cell migratory module that links chronic injury to basal-cell dysplasia, senescence-resistance, and fibrotic-remodeling. Idiopathic pulmonary fibrosis (IPF) is a high-mortality progressive lung-scarring disease (~3M patients globally, median survival 3–5 years from diagnosis, ~50,000 deaths/year in the US) with only two FDA-approved disease-modifying therapies: nintedanib (Ofev, Boehringer Ingelheim, a triple angiokinase inhibitor targeting FGFR/PDGFR/VEGFR) and pirfenidone (Esbriet, Genentech/Roche, an anti-fibrotic + anti-inflammatory small molecule). The active 2026 pipeline includes the integrin αvβ6 inhibitor bexotegrast (Pliant Therapeutics, Phase-2b/3), the PDE4B inhibitor nerandomilast (BI 1015550, Boehringer, Phase-3), and the recombinant-pentraxin-2 zinpentraxin-alfa (Promedior/Roche, Phase-3). (2) AI Drug Discovery / cancer metastasis + RNA splicing + hnRNP M + circular RNA aptamer: GSE335525 (watcher score 6, n=12, Homo sapiens, spatial [Expression profiling by high throughput sequencing], pdat 2026/08/04 = 2 days ago, raw_file_availability 'yes', suppfile CSV) is the FRESHEST score-6 hnRNP-M / circular-RNA-aptamer / RNA-splicing / cancer-metastasis spatial hit in the entire 2026-08-06 scan and a direct RNA-splicing / refractory-cancer / AI-drug-discovery input for the BB AI-drug-discovery + refractory-cancer lane. The GEO title reports that targeting the splicing factor hnRNP M with an endogenous circular RNA aptamer suppresses cancer metastasis, providing a clean n=12 spatial reference for a novel RNA-aptamer therapeutic strategy that targets the splicing factor hnRNP M (heterogeneous nuclear ribonucleoprotein M, HNRNPM) to suppress tumor metastasis. hnRNP M is a major splicing regulator that controls alternative-splicing of cancer-relevant transcripts (CD44, FGFR2, TP53, NUMB, multiple cytoskeletal and EMT transcripts), and circular RNA aptamers (circRNA-aptamers, the next-generation RNA-therapeutic modality beyond ASOs and siRNAs) are an emerging 2026 therapeutic class with intrinsic nuclease-resistance, cell-type-specific delivery potential, and the ability to disrupt protein-RNA or protein-protein interactions. (3) AI Drug Discovery / ferroptosis + tumor metabolism + lactic acid-Chac1 axis: GSE341504 (watcher score 6, n=6, Homo sapiens, metabolism / RNA-seq [A549_LAC], pdat 2026/08/04 = 2 days ago, raw_file_availability 'yes', suppfile TXT) is the FRESHEST score-6 lactic-acid-Chac1 / ferroptosis / tumor-metabolism RNA-seq hit in the entire 2026-08-06 scan and a direct ferroptosis / metabolic-vulnerability / AI-drug-discovery input for the BB AI-drug-discovery + longevity-ferroptosis lane. The GEO title reports that a lactic acid-Chac1 axis regulates ferroptosis-associated cell death and tumor progression, providing a clean n=6 A549 (lung adenocarcinoma) + lactic-acid-treatment RNA-seq atlas that resolves how the metabolite lactic acid (the canonical Warburg-effect byproduct) regulates the glutathione-degradation enzyme Chac1 (ChaC glutathione-specific gamma-glutamylcyclotransferase 1) to modulate ferroptosis sensitivity. Ferroptosis is an iron-dependent regulated cell-death modality (the canonical Stockwell / Dixon paradigm) that is a major 2026 cancer-therapeutic target — the active clinical pipeline includes the GPX4 inhibitors (ML162/ML210 series, JKE-1674), the system-xc⁻ inhibitors (sulfasalazine, sorafenib, erastin analogs), the lipid-peroxidation inhibitors (ferrostatin-1, liproxstatin-1), and the FSP1 (AIFM2) inhibitors. The lactic-acid-Chac1 axis is a uniquely tractable metabolic-vulnerability because lactic acid is the dominant tumor-microenvironment metabolite in solid tumors (Warburg effect), and Chac1 is the rate-limiting enzyme in glutathione degradation. --- ## 🎯 Highlights ### 1. Signal 1 — Bioinformatics & Multi-Omics / IPF + lung fibrosis + TGFβ1 + KRT17-Stratifin + dysplastic alveolar-basal metaplasia: GSE330876 (watcher score 9, n=14, Homo sapiens, spatial + expression profiling by high throughput sequencing + genome binding/occupancy profiling by high throughput sequencing, pdat 2026/08/04 = 2 days ago, raw_file_availability 'yes', suppfile H5, MTX, RDS, TAR, TBI, TSV, watcher query 'lung fibrosis single-cell') is the FRESHEST score-9 TGFβ1-KRT17-stratifin / dysplastic-alveolar-basal-metaplasia / IPF-fibrosis spatial hit in the entire 2026-08-06 scan and a direct IPF / lung-fibrosis / anti-fibrotic input for the BB bioinformatics + anti-fibrotic lane. The GEO title reports that chronic TGFβ1 signaling drives dysplastic alveolar-basal metaplasia through a KRT17-stratifin migratory complex, providing a clean n=14 spatial transcriptomics atlas (H5/MTX/RDS/TAR/TBI/TSV raw files) that resolves how sustained TGFβ1 signaling in airway-basal cells drives a KRT17+/14-3-3σ (stratifin/SFN) migratory complex that mediates dysplastic alveolar-basal metaplasia — a precursor lesion to IPF (idiopathic pulmonary fibrosis) and mucinous adenocarcinoma. TGFβ1 is the canonical master regulator of tissue fibrosis (the canonical IPF / MASH / systemic-sclerosis / Duchenne-muscle-fibrosis cytokine), and the KRT17 + stratifin (14-3-3σ, SFN) complex is a freshly-characterized basal-cell migratory module that links chronic injury to basal-cell dysplasia, senescence-resistance, and fibrotic-remodeling. Idiopathic pulmonary fibrosis (IPF) is a high-mortality progressive lung-scarring disease (~3M patients globally, median survival 3–5 years from diagnosis, ~50,000 deaths/year in the US) with only two FDA-approved disease-modifying therapies: nintedanib (Ofev, Boehringer Ingelheim, a triple angiokinase inhibitor targeting FGFR/PDGFR/VEGFR) and pirfenidone (Esbriet, Genentech/Roche, an anti-fibrotic + anti-inflammatory small molecule). The active 2026 pipeline includes the integrin αvβ6 inhibitor bexotegrast (Pliant Therapeutics, Phase-2b/3), the PDE4B inhibitor nerandomilast (BI 1015550, Boehringer, Phase-3), and the recombinant-pentraxin-2 zinpentraxin-alfa (Promedior/Roche, Phase-3). The 2-day-old freshness is unusual for an IPF spatial atlas and the n=14 spatial + expression + ChIP-seq design is a tractable input for BB anti-fibrotic + IPF briefs. It complements yesterday's id:60 GSE302356 LAM-niche single-cell + spatial atlas to define a unified IPF + LAM + KRT17-basal-cell reference for BB anti-fibrotic + rare-lung-disease briefs. Four-axis score: peptide 0/3, AI-agent infrastructure 3/3 (spatial + expression + ChIP-seq + raw files + 2-days-fresh), longevity 1/3, low-cost/ease 3/3, translational fit 3/3 = 10/15. Citation: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330876. ### 2. Signal 2 — AI Drug Discovery / cancer metastasis + RNA splicing + hnRNP M + circular RNA aptamer: GSE335525 (watcher score 6, n=12, Homo sapiens, spatial [Expression profiling by high throughput sequencing], pdat 2026/08/04 = 2 days ago, raw_file_availability 'yes', suppfile CSV) is the FRESHEST score-6 hnRNP-M / circular-RNA-aptamer / RNA-splicing / cancer-metastasis spatial hit in the entire 2026-08-06 scan and a direct RNA-splicing / refractory-cancer / AI-drug-discovery input for the BB AI-drug-discovery + refractory-cancer lane. The GEO title reports that targeting the splicing factor hnRNP M with an endogenous circular RNA aptamer suppresses cancer metastasis, providing a clean n=12 spatial reference for a novel RNA-aptamer therapeutic strategy that targets the splicing factor hnRNP M (heterogeneous nuclear ribonucleoprotein M, HNRNPM) to suppress tumor metastasis. hnRNP M is a major splicing regulator that controls alternative-splicing of cancer-relevant transcripts (CD44, FGFR2, TP53, NUMB, multiple cytoskeletal and EMT transcripts), and circular RNA aptamers (circRNA-aptamers, the next-generation RNA-therapeutic modality beyond ASOs and siRNAs) are an emerging 2026 therapeutic class with intrinsic nuclease-resistance, cell-type-specific delivery potential, and the ability to disrupt protein-RNA or protein-protein interactions. Cancer metastasis is the dominant cause of cancer-related mortality (~90% of solid-tumor deaths), and the RNA-splicing axis is a rapidly emerging therapeutic class with active clinical assets including the PRMT5 inhibitors (MRTX1719, AMG-193), the SF3B1 modulators (pladienolide B, E7107, H3B-8800), and the hnRNP A1/A2/B1 family being explored by the splicing-target community. The hnRNP M + circRNA-aptamer combination is uniquely novel because it combines a newly-validated splicing target with a next-generation RNA-therapeutic delivery modality. Four-axis score: peptide 0/3, AI-agent infrastructure 3/3, longevity 0/3, low-cost/ease 3/3, translational fit 3/3 = 9/15. Citation: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335525. ### 3. Signal 3 — AI Drug Discovery / ferroptosis + tumor metabolism + lactic acid-Chac1 axis: GSE341504 (watcher score 6, n=6, Homo sapiens, metabolism / RNA-seq [A549_LAC], pdat 2026/08/04 = 2 days ago, raw_file_availability 'yes', suppfile TXT) is the FRESHEST score-6 lactic-acid-Chac1 / ferroptosis / tumor-metabolism RNA-seq hit in the entire 2026-08-06 scan and a direct ferroptosis / metabolic-vulnerability / AI-drug-discovery input for the BB AI-drug-discovery + longevity-ferroptosis lane. The GEO title reports that a lactic acid-Chac1 axis regulates ferroptosis-associated cell death and tumor progression, providing a clean n=6 A549 (lung adenocarcinoma) + lactic-acid-treatment RNA-seq atlas that resolves how the metabolite lactic acid (the canonical Warburg-effect byproduct) regulates the glutathione-degradation enzyme Chac1 (ChaC glutathione-specific gamma-glutamylcyclotransferase 1) to modulate ferroptosis sensitivity. Ferroptosis is an iron-dependent regulated cell-death modality (the canonical Stockwell / Dixon paradigm) that is a major 2026 cancer-therapeutic target — the active clinical pipeline includes the GPX4 inhibitors (ML162/ML210 series, JKE-1674), the system-xc⁻ inhibitors (sulfasalazine, sorafenib, erastin analogs), the lipid-peroxidation inhibitors (ferrostatin-1, liproxstatin-1), and the FSP1 (AIFM2) inhibitors. The lactic-acid-Chac1 axis is a uniquely tractable metabolic-vulnerability because lactic acid is the dominant tumor-microenvironment metabolite in solid tumors (Warburg effect), and Chac1 is the rate-limiting enzyme in glutathione degradation. Four-axis score: peptide 0/3, AI-agent infrastructure 3/3, longevity 1/3, low-cost/ease 3/3, translational fit 3/3 = 10/15. Citation: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341504. ### 4. Four-axis decision gate — GSE330876 (IPF + TGFβ1 + KRT17-stratifin + dysplastic-alveolar-basal-metaplasia spatial): peptide 0/3, AI-agent infrastructure 3/3, longevity 1/3, low-cost/ease 3/3, translational fit 3/3 = 10/15; GSE335525 (hnRNP M + circRNA-aptamer + cancer-metastasis spatial): peptide 0/3, AI-agent infrastructure 3/3, longevity 0/3, low-cost/ease 3/3, translational fit 3/3 = 9/15; GSE341504 (lactic-acid-Chac1 + ferroptosis + A549 RNA-seq): peptide 0/3, AI-agent infrastructure 3/3, longevity 1/3, low-cost/ease 3/3, translational fit 3/3 = 10/15. Combined four-axis score = 29/45 with anti-fibrotic + IPF leverage dominated by GSE330876 (TGFβ1 + KRT17-stratifin + dysplastic-alveolar-basal-metaplasia + 2-days-fresh + spatial + ChIP-seq), AI-drug-discovery + RNA-therapeutic leverage dominated by GSE335525 (hnRNP M + circRNA-aptamer + cancer-metastasis + 2-days-fresh + novel RNA-modality), and ferroptosis + metabolic-vulnerability leverage dominated by GSE341504 (lactic-acid-Chac1 + A549 + Warburg-effect + 2-days-fresh). All three accessions are absent from id:54-id:60 (NOVEL 3/3). Next action: ingest raw H5/MTX/RDS/TAR/TBI/TSV matrices for GSE330876; build a KRT17-stratifin migratory-complex signature panel stratified by TGFβ1-responder vs non-responder basal-cell subsets for BB IPF + anti-fibrotic briefs; integrate GSE335525 hnRNP-M circRNA-aptamer spatial atlas with yesterday's GSE296517 breast-cancer + focused-ultrasound + gemcitabine BR54 trial spatial atlas to define a unified RNA-splicing + refractory-cancer spatial reference for BB AI-drug-discovery + RNA-therapeutic briefs; benchmark GSE341504 lactic-acid-Chac1 axis transcriptomic signatures against yesterday's GSE308816 polyamine-metabolism + aging-muscle atlas and yesterday's GSE330351 ferritin / iron-homeostasis / fibroblast-remodeling atlas to nominate a ferroptosis + metabolic-vulnerability + longevity combination panel before commissioning any wet-lab follow-up. --- ## 💼 Next Steps - **[Open GSE330876 in GEO (IPF + TGFβ1 + KRT17-stratifin spatial)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330876)** - **[Open GSE335525 in GEO (hnRNP M + circRNA-aptamer cancer metastasis)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335525)** - **[Open GSE341504 in GEO (lactic acid-Chac1 + ferroptosis A549 RNA-seq)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341504)** - **[Request IPF + RNA-therapeutic + ferroptosis brief](https://brownbio.tech/services/ai-drug-discovery#brief)** --- ## 📡 Provenance - **Source:** research-watcher (PubMed/GEO scan, 27 query families × Brown Biotech pipelines) - **Pipeline:** [`brown-biotech-daily-tech-digest`](https://github.com/ohbryt/brown-biotech-platform) — 06:00 KST cron - **Generated:** 2026-08-06 06:10 KST - **Repo:** `ohbryt/brown-biotech-platform` --- _Auto-published by `brown_biotech_research_digest_publisher.py` · [brownbio.tech](https://brownbio.tech) · Decision-ready research, daily._
Brown Biotech Research Digest — 2026-08-06
PubMed/GEO scan · research-watcher · 06:00 KST