Biology subjects

Lee, H. T.

Publications and source records attributed to Lee, H. T..

3 recordsLinked to original sources

bioRxiv2026

Epigenetic Reactivation of Lineage Differentiation to Target Leukemia

Chromatin regulation critically influences gene expression and cancer progression, yet the functions of chromatin adaptors remain incompletely defined. Using focused CRISPR screening, we identified TRIM28, a multi-domain chromatin adaptor, as a dependency in acute leukemia, where its depletion impaired leukemia cell proliferation in vitro and in vivo, while activating neutrophil differentiation programs. Integrative transcriptomic and chromatin profiling revealed that TRIM28 acts as a co-repressor of neutrophil-associated loci independently of H3K9 methylation, and that TRIM28 loss drives terminal differentiation of leukemia cells into functionally mature neutrophil-like cells with reduced leukemic potential. We developed a selective small-molecule TRIM28 inhibitor that binds the TRIM28 PHD-bromodomain, phenocopies TRIM28 loss across biochemical and cellular assays, exhibits low micromolar anti-leukemia activity, induces neutrophil differentiation, and synergizes with Menin inhibition. Together, these findings, spanning target discovery, mechanism of action, and chemical probe development, establish TRIM28 as a regulator of myeloid cell fate and a promising pro-differentiation therapeutic target in acute leukemia.

cancer biology↗

bioRxiv2025

Consequences of cannibalism: induced defense and kin discrimination in a rotifer

Resource polyphenisms result in the production of environmentally induced morphs with differential niche use. These striking examples of phenotypic plasticity are taxonomically widespread and ecologically important. However, cannibalism is a frequent repercussion of resource polyphenisms. Despite some benefits, cannibalism is always costly to victims and sometimes costly to the cannibal. Therefore, we here evaluate how morphological and behavioral plastic strategies to minimize these costs may evolve. To better understand the evolution and consequences of cannibalistic polyphenisms, we tested whether rotifers Asplanchna brightwellii possess effective morphological defenses against cannibalism and the ability to discriminate by genetic relationship. We found that small humps produced by vulnerable A. brightwellii limit cannibalism. We also found that cannibals were less likely to attack clonemates than non-kin. The rotifer genus Asplanchna comprises species with varying degrees of resource polyphenism, cannibalism, induced morphological defenses, and behavioral kin discrimination. The observed induced defense and kin discrimination in Asplanchna brightwellii likely represent evolutionary intermediates facilitating the evolution of a unique trimorphic resource polyphenism in congeners.

evolutionary biology↗

bioRxiv2020

Horseshoe crab genomes reveal the evolutionary fates of genes and microRNAs after three rounds (3R) of whole genome duplication

Whole genome duplication (WGD) has occurred in relatively few sexually reproducing invertebrates. Consequently, the WGD that occurred in the common ancestor of horseshoe crabs ~135 million years ago provides a rare opportunity to decipher the evolutionary consequences of a duplicated invertebrate genome. Here, we present a high-quality genome assembly for the mangrove horseshoe crab Carcinoscorpius rotundicauda (1.7Gb, N50 = 90.2Mb, with 89.8% sequences anchored to 16 pseudomolecules, 2n = 32), and a resequenced genome of the tri-spine horseshoe crab Tachypleus tridentatus (1.7Gb, N50 = 109.7Mb). Analyses of gene families, microRNAs, and synteny show that horseshoe crabs have undergone three rounds (3R) of WGD, and that these WGD events are shared with spiders. Comparison of the genomes of C. rotundicauda and T. tridentatus populations from several geographic locations further elucidates the diverse fates of both coding and noncoding genes. Together, the present study represents a cornerstone for a better understanding of the consequences of invertebrate WGD events on evolutionary fates of genes and microRNAs at individual and population levels, and highlights the genetic diversity with practical values for breeding programs and conservation of horseshoe crabs.

evolutionary biology↗