Force-sensing and signaling logic of cells
More to come.
Amplification of oncogenes on extrachromosomal DNA in cancer cells
Our work on cancer-driving genes (oncogenes) showed that these genes, often copy-number-amplified outside chromosomes on extrachromosomal DNA (ecDNA), can be activated by clustering with one another in cancer cells. ecDNA clustering promotes active oncogene transcription, allowing cross-activation between molecules and intermolecular interactions between non-coding regulatory elements. We also demonstrated a strategy for isolating ecDNAs from cancer cells using a method called CRISPR-CATCH to analyze their genetic sequences and epigenetic features. Using this approach, we identified mutations on ecDNAs, discovered that their oncogene promoters have decreased DNA methylation, and mapped out the specialized ecDNA structures with rearranged oncogene sequences and enhancer elements in cancer cells. This work showed how cancer genomes can have dysregulated oncogene expression by forming circular ecDNAs, as well as their impact on cancer cell fitness.
Key Publications:
Hung KL et al. Nature 2021
Hung KL et al. Nature Structural & Molecular Biology 2022
Hung KL et al. Nature Genetics 2022 (research briefing)
Hung KL et al. Nature 2024
Manipulating immune cell differentiation via cytokine stimulation and genome editing
We developed a workflow for engineering primary human B cells to express therapeutic proteins. Using an ex vivo multi-step culturing strategy, we were able to differentiate engineered cells into plasma cells and engraft them into mice to stably secrete exogenous proteins into peripheral blood. As plasma cells can be long-lived (decades!), we used this proof-of-concept study to demonstrate that engineered B cells have the potential to be a new form of long-term protein therapy.
Key Publications:
Hung KL et al. Molecular Therapy 2018
Cheng RYH, Hung KL et al. Nature Communications 2022