Biology subjects

Chang, E. S.

Publications and source records attributed to Chang, E. S..

4 recordsLinked to original sources

bioRxiv2026

A chromosome-level reference genome for the colonial marine hydrozoan Podocoryna americana

Cnidarians are important models for the studying the evolution of animal development, regeneration, cell type differentiation, and allorecognition. The marine hydrozoan Podocoryna americana is related to the well-established model species Hydractinia symbiolongicarpus. Although both species possess a sessile polyp stage, P. americana differs in that it also has a free-swimming medusa (jellyfish) stage in its life cycle. We used a combination of PacBio CLR long-read and Illumina Hi-C short-read genome sequencing to produce a chromosome-level genome assembly for P. americana. The final assembly is 327 Mbp in total length with 17 chromosome-scale scaffolds representing 98% of the assembly. Comprehensive functional annotation with BRAKER3 generated a total of 19,085 predicted protein-coding genes in this assembly, covering 91.2% of the metazoan BUCSO gene set. Comparison of the P. americana genome to other chromosome-level cnidarian genome assemblies revealed a high degree of macrosynteny conservation, and ortholog identification and gene family evolution analysis identified 522 expanded and 1,026 contracted gene families in P. americana. This high-quality, chromosome-level genome assembly of P. americana will be an invaluable resource for researchers studying the evolution of development, regeneration, and allorecognition in cnidarians and other metazoans.

genomics↗

bioRxiv2025

CRISPR-Induced NUT Suppression Promotes Differentiation and Enhances Trop2-Targeted Immunocytokine Response in NUT Carcinoma

NUT carcinoma (NC) is an aggressive malignancy driven by NUTM1 gene rearrangements with limited therapeutic options. Here, we show that direct suppression of NUTM1 using CRISPR/Cas9 induces squamous-like differentiation and upregulates TROP2 expression in NC cells. Building on this finding, we developed a TROP2-interferon beta (IFN-{beta}) mutein immunocytokine that selectively targets TROP2-expressing tumors. Combined NUTM1 suppression and TROP2-targeted immunotherapy synergistically enhanced cytotoxic and immune-mediated responses in vitro. Transcriptomic and spatial analyses of NC patient tumors revealed that differentiation status correlates with TROP2 expression, upregulated immune pathways, and favorable clinical outcomes. Our results suggest that overcoming differentiation blockade not only alters tumor phenotype but also creates a more immune-permissive microenvironment. These findings highlight the therapeutic potential of sequential tumor reprogramming followed by targeted immunotherapy in treating NC and propose a broader strategy for overcoming differentiation blockade in fusion-driven cancers.

cancer biology↗

bioRxiv2023

The genome of the colonial hydroid Hydractinia reveals their stem cells use a toolkit of genes shared with all animals

Hydractinia is a colonial marine hydroid that exhibits remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, H. symbiolongicarpus and H. echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult male H. symbiolongicarpus and identified cell type markers for all major cell types, including key i-cell markers. Orthology analyses based on the markers revealed that Hydractinias i-cells are highly enriched in genes that are widely shared amongst animals, a striking finding given that Hydractinia has a higher proportion of phylum-specific genes than any of the other 41 animals in our orthology analysis. These results indicate that Hydractinias stem cells and early progenitor cells may use a toolkit shared with all animals, making it a promising model organism for future exploration of stem cell biology and regenerative medicine. The genomic and transcriptomic resources for Hydractinia presented here will enable further studies of their regenerative capacity, colonial morphology, and ability to distinguish self from non-self.

genomics↗

bioRxiv2022

XY sex determination in a cnidarian

Sex determination occurs across animal species, but most of our knowledge about the mechanisms of sex determination comes from only a handful of bilaterian taxa. This limits our ability to infer the evolutionary history of sex determination within animals. In this study, we generated a linkage map of the genome of the colonial cnidarian Hydractinia symbiolongicarpus and used this map to determine that this species has an XX/XY sex determination system. We delineate the pseudoautosomal and non-recombining regions of the Y chromosome and show that the latter encodes a number of genes with male gonad-specific expression. These findings establish Hydractinia as a tractable non-bilaterian model system for the study of sex determination. Significance StatementWhat determines whether an animal is male or female? The answer depends on the species. Some rely on signals from their environment, while others take cues from their genome. Most of what we understand about sex determination comes from traditional model organisms (such as mice, flies, and worms) or groups of well-studied vertebrates and insects. Studying sex determination in other animals, especially those from phyla that diverged early in animal evolution, would allow us to better understand how sex has evolved across the animal kingdom and could reveal pathways present in the eumetazoan ancestor >600 million years ago. In this study, we show that the cnidarian Hydractinia symbiolongicarpus has XY sex determination, establishing this species as a model system for sex determination in an understudied group of animals.

genetics↗