Research interests

I work on chemical modifications of biological macromolecules and their role in epigenetic adaptation; or, how cells change what their genome means without changing what it says.

Current research

Clinical sequencing of tumors has revealed histone mutations that appear repeatedly across multiple patients. I am testing what that recurrence implies, what these mutations do to a cell, and through which mechanism they act.

• Selection and opportunity in cancer genomes. Many histone mutations recur because they are likely, not because they are selected. I use modeling approaches to find selected mutations that recurrence alone overlooks.
• Functional consequences across cellular contexts. A lesion can be innocuous in one context and transforming in another. I screen barcoded histone libraries across cell lines to map where that boundary falls.
• Biochemical models of chromatin. I reconstitute defined nucleosome substrates, “designer chromatin,” to isolate the biochemical mechanism of a histone mutation.

Measurements of nucleosomes are scattered across decades of papers, each using their own naming conventions.

• I built nucleosomekb, an open index where you can ask for a histone mark or mutation, a whole nucleosome, a sub-nucleosomal particle, or an array – and see what has been measured.

Earlier work

• Protein engineering by directed evolution to detect rare combinatorial DNA modifications in mammalian genomes. The probes underpin the genome-wide HM-DyadCap maps published in Nucleic Acids Research this year.
• High-throughput genome engineering using CRISPR-Cas12a (CASTLING) for library-scale gene tagging in yeast and mammalian cells.

Fellowships and awards

• EMBO Postdoctoral Research Fellowship, 2022–2024
• Biomedizin-Preis (Young Talent Award), 2023
• Rainer Rudolph Prize, 2022
• Add-on Fellowship for Interdisciplinary Life Science, Joachim Herz Stiftung, 2019–2022
• Fellow of the International Max Planck Research School for Living Matter, 2017–2021