fairfolio
Saved Projects

Identification of a Novel TBX2-Dependent Mechanism Linking Pericyte Dynamics to Abnormal Vasculature in Lung Adenocarcinoma

ISEF · 2026 Biomedical and Health Sciences

Kakkad, Yatharth · Pine View School

Overview

Tumor growth in lung adenocarcinoma (LUAD) – the most prevalent form of lung cancer, with a 5-year survival rate below 20% – is promoted by abnormal vasculature. Importantly, the mechanisms driving these vascular defects remain incompletely characterized. TBX2, a transcription factor selectively expressed by pericytes during capillary network assembly, is significantly downregulated in LUAD. Given the unknown role of TBX2 in angiogenesis, this study utilized a transgenic zebrafish model to elucidate its function in vivo, then proceeded to evaluate its relevance to LUAD. Loss of the zebrafish TBX2 homolog, tbx2b, was achieved via CRISPR-Cas9. Confocal imaging at 3 and 5 days post-fertilization (dpf) revealed dose-dependent pericyte loss; tbx2b -/- embryos demonstrated pericyte depletion (p < 0.0001) and failed proliferation between endpoints (p < 0.0001). This lack of mural cell support caused progressive vessel dilation (p < 0.01 at 5 dpf), mirroring the LUAD phenotype. To evaluate disease relevance, scRNA-seq data from LUAD patients was analyzed through a Bayesian workflow. TBX2 expression was positively associated (>98% probability) with pericyte proliferation and cell adhesion signatures, demonstrating mechanistic conservation with the tbx2b -/- zebrafish phenotype and significance of TBX2 loss in LUAD. Further analysis involving the TCGA-LUAD cohort identified miR-130b as a potential post-transcriptional repressor of TBX2 due to its upregulation in LUAD (p < 0.0001), 7-mer seed match, and negative correlation with TBX2 expression (rho = -0.31, p < 0.0001). Finally, to restore normal pericyte-endothelial cell dynamics in LUAD, a fusion protein was designed de novo in silico to reanchor pericytes to vessel walls, advancing towards normalizing LUAD vasculature.

Awards (1)

  • First Award of $6,000 $6,000

Competition history

Resources

Related projects

Closest projects by meaning, across every fair and year in the corpus.

Browse more like this

Source: Regeneron International Science and Engineering Fair

Save projects to your library

Sign in with Google to keep track of projects you find interesting, organized into folders. An account also raises your daily allowance for “Has this been done?”, and lets you create a key for the MCP server with a much higher limit than anonymous use. Browsing stays public.

Continue with Google