Lab News

We are thrilled to announce that Lilly has successfully defended her PhD! Her research focused on monitoring genome editing by visualizing DNA repair. She developed a high-throughput off-target identification method, enabling tracking of off-targets for thousands of human guide RNAs. A huge congratulations, Dr. van den Venn!

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Young earned his Ph.D. in Biological Sciences from Seoul National University (South Korea) in 2023, where he worked in Dr. V. Narry Kim’s lab, focusing on the molecular and structural insights of siRNA and miRNA production by human Dicer. In November 2024, he joined the Corn Lab as a postdoctoral researcher, with a research focus on leveraging CRISPR technology to address fundamental biological questions.

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Erik Basha received his Bachelor’s degree in Biochemistry and Molecular Biology from the University of Bern in 2023.  Erik joined the Corn Lab in October 2024. He is currently working on his Master’s thesis, focusing on the characterization of unexplored interactions between genes involved in DNA damage repair and other essential cellular mechanisms.

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Our warmest congratulations to Charles on successfully defending his PhD! His commitment and hard work have undoubtedly led to this well-deserved achievement. He developed an innovative, high-sensitivity in situ/in vivo system for monitoring homology search during DNA double-stranded break homology-directed repair (DSBR/HDR). Well done, Dr. Yeh!

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Huge congratulations to Marija on completing her PhD! Her dedication and hard work have paid off! Using a genome-wide CRISPR screen, Marija identified mediators of enucleation in red blood cells. We’re thrilled she’ll continue in the lab as a postdoc- here’s to more amazing accomplishments, Dr. Banovic!

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Jenna Rode received her Bachelor’s degree in Molecular and Cell Biology from UC Berkeley in 2023, working in the lab of Professor Gary Karpen on the role of heterochromatin binding proteins in nuclear organization. Jenna joined the Corn lab in September 2024. She is currently working on her Master’s thesis, focusing on discovering novel mechanisms of DNA-protein crosslink degradation.

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On September 18-19 2024, the Corn Lab hosted an engaging in-person DDREAMM team retreat in Zurich, bringing together researchers for two days of scientific presentations, fruitful discussions, and the exchange of fresh ideas. The event highlighted synergies between the Jackson/Corn lab and fostered brainstorming sessions focused on the latest technologies, scientific advancements, and the evolving landscape of publications in the era of AI and preprints.

Participants also enjoyed valuable networking opportunities, including a scenic hike from Uetliberg to Felsenegg, offering breath-taking views of Zurich and its surroundings.

The retreat was highly effective, sparking new collaborations.

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The Corn lab  held an exciting retreat in Unterwasser (Toggenburg region, St. Gallen) on September 10th and 11th, offering a perfect blend of productivity and engagement. The retreat featured focused writing workshops, sessions on scientific illustration tools, and in-depth discussions on career development, including negotiation skills. Lab members had a valuable opportunity to network, share ideas, and explore future career paths, all while enjoying the beautiful surroundings.

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CRISPR-Cas9 gene editing is widely used to introduce targeted mutations in cells and organisms. During the gene editing process, Cas enzymes induces a double-strand break at a target genomic site that is subsequently repaired by on of two mechanisms: error-prone nonhomologous end joining (NHEJ) that results in genomic insertions and deletions (indels), or templated homology-directed repair (HDR) to precisely insert, delete, or replace a genomic sequence.  Have you ever wondered why CRISPR-Cas mediated HDR editing is so efficient in some cells but terribly inefficient in others? Struggling with gene editing in your cells? We’ve got the solution you’ve been looking for!

We are excited to announce a significant advancement in our understanding of CRISPR-Cas9-mediated HDR through genome-wide screening conducted in Fanconi anemia (FA) patient lymphoblastic cell lines. Our research led by Postdoc Erman Karasu uncovered a single suppressor of CRISPR-Cas9 mediated HDR, revealing that exonuclease TREX1 plays a critical role in reducing HDR efficiency when the repair template is either single-stranded or linearized double-stranded DNA. TREX1 expression serves as a biomarker for CRISPR-Cas9-mediated HDR, and high levels of TREX1, observed in various cell types including U2OS, Jurkat, MDA-MB-231, primary T cells, and hematopoietic stem and progenitor cells (HSPCs), are predictive of poor HDR outcomes. Moreover, we have demonstrated that HDR efficiency can be significantly improved, by 2- to 8-fold, through either knockout of TREX1 or the use of chemically protected single-stranded DNA templates that are resistant to TREX1 activity. Namely, phosphorothioate 3’ end protection is sufficient for fast inexpensive improvements to HDR in contexts with appreciable TREX1 expression. These strategies offer promising avenues for enhancing CRISPR-Cas9–mediated HDR, particularly in cell types with high TREX1 expression.

Overall, our data sheds mechanistic light on why donor template protection increases HDR, provide a concrete biomarker for the targeted use of template protection, and resolve long-standing confusion around why editing works like a breeze in some cells, but fails miserably in others. This breakthrough holds substantial potential for advancing research and therapeutic applications.

For more, check out our paper, it is now out in Nature Biotechnology!

Don’t miss the explainer video highlighting Erman’s work!

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