Portrait of Ben

Hi, I’m Ben!

I am an Associate Research Scholar in the Department of Chemistry at Princeton University, working in the lab of Prof. Tom Muir.

My research asks why only a few histone mutations drive cancer.

Before that, I developed proteins that recognize rare enzymatic DNA modifications with Prof. Daniel Summerer for my PhD in Chemical Biology at TU Dortmund University.

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.

Nucleosomes bearing different single-site mutations

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

Protocols

As in all biology, good protocols evolve over time, but printed copies often don’t. Here are my version-controlled write-ups:

Recipes Version
check

Publications

  • HM-DyadCap – capture and mapping of 5-hydroxymethylcytosine/5-methylcytosine CpG dyads in mammalian DNA
    L. Engelhard*; D. Schiller*; M. S. Zambrano-Mila; K. Keliuotyte; B. Buchmuller; S. Tiwari; J. Imig; A. Simeone; C. Schröter; S. Becker; D. Summerer.
    Nucleic Acids Res. 2026, 54(8), gkag389. doi:10.1093/nar/gkag389 DOI PMID:42023651 PMID PMC13103736 PMC
    Impact: Demonstrated that our engineered MBD (Buchmuller et al., JACS 2022) is capable of profiling hmC/mC marks in mammalian genomes
  • Evolved Readers of 5‐Carboxylcytosine CpG Dyads Reveal a High Versatility of the Methyl‐CpG‐Binding Domain for Recognition of Noncanonical Epigenetic Marks
    B. Kosel; K. Bigler; B. C. Buchmuller; S. R. Acharyya; R. Linser; D. Summerer.
    Angew. Chem. Int. Ed. 2024, 63(17), e202318837. doi:10.1002/anie.202318837 DOI PMID:38284298 PMID
    Impact: Demonstrated the MBD scaffold can be evolved towards 5-carboxylcytosine recognition despite the stark chemical difference from the natural substrate
  • Epigenetic CpG duplex marks probed by an evolved DNA reader via a well-tempered conformational plasticity
    H. Singh; C. K. Das; B. C. Buchmuller; L. V. Schäfer; D. Summerer; R. Linser.
    Nucleic Acids Res. 2023, 51(12), 6495–6506. doi:10.1093/nar/gkad134 DOI PMID:36919612 PMID PMC10325892 PMC
    Impact: Revealed molecular basis of hmC/mC reader selectivity through conformational plasticity using combined insights from NMR spectroscopy, MD simulations, and directed evolution
  • A translational repression reporter assay for the analysis of RNA-binding protein consensus sites
    J. Nowacki; M. Malenica; S. Schmeing; D. Schiller; B. Buchmuller; G. Amrahova; P. ‘t Hart.
    RNA Biol. 2023, 20(1), 85–94. doi:10.1080/15476286.2023.2192553 DOI PMID:36946649 PMID PMC10038052 PMC
    Impact: Expanded the translational repression assay for linear RNA sequences enabling broader RNA-binding protein studies
  • Imaging-Based In Situ Analysis of 5‑Methylcytosine at Low Repetitive Single Gene Loci with Transcription-Activator-Like Effector Probes
    A. Jung; A. Munõz-López; B. C. Buchmuller; S. Banerjee; D. Summerer.
    ACS Chem. Biol. 2023, 18(2), 230–236. doi:10.1021/acschembio.2c00857 DOI PMID:36693632 PMID PMC9942090 PMC
    Impact: Extended TALE imaging to low-repetitive single gene loci through signal amplification strategies
  • A high-throughput effector screen identifies a novel small molecule scaffold for inhibition of ten-eleven translocation dioxygenase 2
    S. Palei; J. Weisner; M. Vogt; R. Gontla; B. Buchmuller; C. Ehrt; T. Grabe; S. Kleinbölting; M. Müller; G. H. Clever; D. Rauh; D. Summerer.
    RSC Med. Chem. 2022, 13(12), 1540–1548. doi:10.1039/d2md00186a DOI PMID:36545435 PMID PMC9749932 PMC
    Impact: Identified a novel quinoline-based TET2 inhibitor scaffold through high-throughput screening of 31,500 compounds
  • Evolved DNA Duplex Readers for Strand-Asymmetrically Modified 5‑Hydroxymethylcytosine/5-Methylcytosine CpG Dyads
    B. C. Buchmuller; J. Dröden; H. Singh; S. Palei; M. Drescher; R. Linser; D. Summerer.
    JACS 2022, 144(7), 2987–2993. doi:10.1021/jacs.1c10678 DOI PMID:35157801 PMID PMC8874921 PMC
    Impact: First affinity probes enabling selective enrichment of strand-asymmetric epigenetic DNA marks from genomic DNA
  • Engineered TALE Repeats for Enhanced Imaging‐Based Analysis of Cellular 5‐Methylcytosine
    Á. Muñoz‐López; A. Jung; B. Buchmuller; J. Wolffgramm; S. Maurer; A. Witte; D. Summerer.
    ChemBioChem 2021, 22(4), 645–651. doi:10.1002/cbic.202000563 DOI PMID:32991020 PMID PMC7894354 PMC
    Impact: Engineered 5mC-binding TALE repeats for imaging-based quantification of DNA methylation at repetitive loci
  • Light‐Activation of DNA‐Methyltransferases
    J. Wolffgramm; B. Buchmuller; S. Palei; Á. Muñoz‐López; J. Kanne; P. Janning; M. R. Schweiger; D. Summerer.
    Angew. Chem. Int. Ed. 2021, 60(24), 13507–13512. doi:10.1002/anie.202103945 DOI PMID:33826797 PMID PMC8251764 PMC
    Impact: First direct optical control of DNMT catalysis enabling insights into cancer-related mutations and programmable site-specific methylation
  • Light-Activatable TET-Dioxygenases Reveal Dynamics of 5‑Methylcytosine Oxidation and Transcriptome Reorganization
    S. Palei; B. Buchmuller; J. Wolffgramm; A. Muñoz-Lopez; S. Jung; P. Czodrowski; D. Summerer.
    JACS 2020, 142(16), 7289–7294. doi:10.1021/jacs.0c01193 DOI PMID:32286069 PMID
    Impact: First temporal control of TET dioxygenase activity in mammalian cells enabling time-resolved monitoring of methylation dynamics and transcriptome reorganization
  • CRISPR-Cas12a–assisted PCR tagging of mammalian genes
    J. Fueller; K. Herbst; M. Meurer; K. Gubicza; B. Kurtulmus; J. D. Knopf; D. Kirrmaier; B. C. Buchmuller; G. Pereira; M. K. Lemberg; M. Knop.
    J. Cell Biol. 2020, 219(6), e201910210. doi:10.1083/jcb.201910210 DOI PMID:32406907 PMID PMC7265327 PMC
    Impact: Extended our CASTLING approach (Buchmuller et al., Nat. Commun. 2019) for gene editing to mammalian cells with up to 60% in-frame tagging efficiency; now widely adopted for endogenous protein tagging studies
  • Designer Receptors for Nucleotide‐Resolution Analysis of Genomic 5‐Methylcytosine by Cellular Imaging
    Á. Muñoz‐López; B. Buchmuller; J. Wolffgramm; A. Jung; M. Hussong; J. Kanne; M. R. Schweiger; D. Summerer.
    Angew. Chem. Int. Ed. 2020, 59(23), 8927–8931. doi:10.1002/anie.202001935 DOI PMID:32167219 PMID PMC7318601 PMC
    Impact: First nucleotide-resolution imaging of 5mC in single cells; enabled direct correlation between epigenetic marks and transcription factor recruitment
  • Complete Profiling of Methyl-CpG-Binding Domains for Combinations of Cytosine Modifications at CpG Dinucleotides Reveals Differential Read-out in Normal and Rett-Associated States
    B. C. Buchmuller; B. Kosel; D. Summerer.
    Sci. Rep. 2020, 10(1), 4053. doi:10.1038/s41598-020-61030-1 DOI PMID:32132616 PMID PMC7055227 PMC
    Impact: First comprehensive profiling of the human MBD protein family revealing differential recognition of oxidized CpG marks by Rett syndrome-associated MeCP2 mutations
  • Pooled clone collections by multiplexed CRISPR-Cas12a-assisted gene tagging in yeast
    B. C. Buchmuller*; K. Herbst*; M. Meurer; D. Kirrmaier; E. Sass; E. D. Levy; M. Knop.
    Nat. Commun. 2019, 10(1), 2960. doi:10.1038/s41467-019-10816-7 DOI PMID:31273196 PMID PMC6609715 PMC
    Impact: CASTLING enables rapid construction of yeast clone libraries with >90% tagging efficiency; method adapted for mammalian gene tagging (Fueller et al., J. Cell Biol. 2020) and cited in advanced Cas12a engineering studies
  • Programmable Protein–DNA Cross-Linking for the Direct Capture and Quantification of 5‑Formylcytosine
    M. Gieß; A. Muñoz-López; B. Buchmuller; G. Kubik; D. Summerer.
    JACS 2019, 141(24), 9453–9457. doi:10.1021/jacs.9b01432 DOI PMID:31180648 PMID
    Impact: Advanced TALE-based nucleobase targeting from recognition to covalent crosslinking for sensitive 5fC quantification
  • Overcoming conservation in TALE–DNA interactions: a minimal repeat scaffold enables selective recognition of an oxidized 5-methylcytosine
    S. Maurer; B. Buchmuller; C. Ehrt; J. Jasper; O. Koch; D. Summerer.
    Chem. Sci. 2018, 9(36), 7247–7252. doi:10.1039/c8sc01958d DOI PMID:30288245 PMID PMC6148557 PMC
    Impact: Developed GRPr-targeting PET tracers with high binding affinity as potential diagnostic imaging tools for prostate and breast cancer
  • Genome-wide C-SWAT library for high-throughput yeast genome tagging
    M. Meurer; Y. Duan; E. Sass; I. Kats; K. Herbst; B. C. Buchmuller; V. Dederer; F. Huber; D. Kirrmaier; M. Štefl; K. V. Laer; T. P. Dick; M. K. Lemberg; A. Khmelinskii; E. D. Levy; M. Knop.
    Nat. Methods 2018, 15(8), 598–600. doi:10.1038/s41592-018-0045-8 DOI PMID:29988096 PMID
    Impact: Created a genome-wide acceptor library (5,661 strains) enabling rapid swapping of tags and regulatory elements; widely adopted for yeast functional genomics
  • Monomeric and Dimeric 68Ga-Labeled Bombesin Analogues for Positron Emission Tomography (PET) Imaging of Tumors Expressing Gastrin-Releasing Peptide Receptors (GRPrs)
    C. Liolios; B. Buchmuller; U. Bauder-Wüst; M. Schäfer; K. Leotta; U. Haberkorn; M. Eder; K. Kopka.
    J. Med. Chem. 2018, 61(5), 2062–2074. doi:10.1021/acs.jmedchem.7b01856 DOI PMID:29432691 PMID
    Impact: Potential diagnostic tools for prostate and breast cancer
* denotes equal contribution ORCID: 0000-0002-4915-5949