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Leong, K.

Publications and source records attributed to Leong, K..

2 recordsLinked to original sources

Spatiotemporal Mapping of brain cilia length and orientation reveals region-specific Oscillation

In this study, we conducted high-throughput spatiotemporal analysis of primary cilia length and orientation across 22 mouse brain regions. We developed automated image analysis algorithms, which enabled us to examine over 10 million individual cilia, generating the largest spatiotemporal atlas of cilia. We found that cilia length and orientation display substantial variations across different brain regions and exhibit fluctuations over a 24-hour period, with region-specific peaks during light-dark phases. Our analysis revealed unique orientation patterns of cilia at 45{degrees} intervals, suggesting that cilia orientation within the brain is not random but follows specific patterns. Using BioCycle, we identified circadian rhythms of cilia length in five brain regions: nucleus accumbens core, somatosensory cortex, and three hypothalamic nuclei. Our findings present novel insights into the complex relationship between cilia dynamics, circadian rhythms, and brain function, highlighting cilia crucial role in the brains response to environmental changes and regulation of time-dependent physiological processes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/546950v3_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@153135corg.highwire.dtl.DTLVardef@11c1d7eorg.highwire.dtl.DTLVardef@d47014org.highwire.dtl.DTLVardef@10a65ca_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

A histone methylation-MAPK signaling axis drives durable epithelial-mesenchymal transition in hypoxic pancreas cancer

Here, we show that hypoxia drives especially long-lasting epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) primarily through a positive-feedback histone methylation-MAPK signaling axis. We find that transformed cells preferentially undergo EMT in hypoxic tumor regions in multiple model systems and that hypoxia drives a cell-autonomous EMT in PDAC cells which, unlike EMT in response to growth factors, can last for weeks. We further demonstrate that hypoxia reduces histone demethylase KDM2A activity, suppresses PP2 family phosphatase expression, and activates MAPKs to post-translationally stabilize histone methyltransferase NSD2, leading to an H3K36me2-dependent EMT in which hypoxia-inducible factors play only a supporting role. This mechanism can be antagonized in vivo by combinations of MAPK inhibitors that may be effective in multi-drug therapies designed to target EMT.

cancer biology↗