We study how life reads, maintains, and changes its own code.

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DNA Damage, Repair & Genome Architecture

DNA is under constant assault from UV light, chemical adducts, and replication stress, and cells have evolved intricate machinery to find and fix the damage before it becomes a mutation. We map nucleotide excision repair genome-wide, at single-nucleotide resolution, using XR-seq and Damage-seq across bacteria, plants, worms, and human cells. A growing thread of this work traces how the genome's 3D architecture is itself reorganized by UV damage — and how that reorganization feeds back into how efficiently the damage gets repaired.

• Transcription-coupled repair and the Mfd/TRCF translocase, from E. coli to Mycobacterium
• UV-induced 3D genome reorganization and its role in the damage response
• Chromatin context and repair dynamics in C. elegans and Arabidopsis
• Cross-species comparisons of XPA-dependent excision repair

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GPCR & Receptor Evolution

G protein-coupled receptors sense everything from light and odorants to hormones and neurotransmitters, and remain the single largest class of drug targets. We use deep evolutionary conservation across GPCR subfamilies to identify the residues that actually define receptor function — how a receptor activates, how it internalizes, and how closely related receptors diverge in the way they signal.

• Evolution-guided residue profiling to decode functional specialization across GPCR subfamilies
• Structural basis of frizzled receptor activation and allosteric regulation
• Conservation analysis of β-adrenergic receptor internalization
• Evolutionary history of calcium-sensing receptors and hyper/hypocalcemia-causing mutations

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Genome Evolution & Variant Interpretation

Mutations are the raw material of evolution, but only some of them matter. We build phylogeny-aware computational methods that use the full evolutionary record — not just a single reference genome — to predict which amino acid substitutions affect protein function, and to detect residues that coevolve across a phylogeny. This work feeds directly into the genetic diagnosis of rare Mendelian disorders, where automated variant-effect prediction still falls short of what the clinic needs.

• PHACTboost — a phylogeny-aware, boosting-based pathogenicity predictor for missense variants
• PHACE — phylogeny-aware detection of molecular coevolution
• Participation in CAGI, the Critical Assessment of Genome Interpretation
• Evolutionary constraints on disease-associated gene families

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Computational Tools & Databases

Good science needs good software. We build and maintain open-source pipelines, web tools, and databases that put our methods directly in the hands of other labs, from genome browsers for repair data to simulators that remove technical bias from sequencing analysis.

• Aquerium, CDvist, SAVER, Phylostat and MiST — our public web tools and databases
• Boquila, an NGS read simulator that eliminates nucleotide bias in sequence analysis
• Automated pipelines for XR-seq and Damage-seq data processing at HPC scale

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Virus & Host Genomics

Viruses evolve under intense pressure from host defense systems, leaving signatures in their genomes that can be read computationally. We study how host mechanisms, from APOBEC3 RNA editing to DNA repair pathways, shape viral genome evolution, and what that means for how these viruses persist and spread.

• APOBEC3-mediated RNA editing and its evasion in monkeypox virus (MPXV) transcripts
• SARS-CoV-2 genomic surveillance and mutational analysis
• Host repair factors and their interaction with viral genomes