Geisel School of Medicine at Dartmouth College
We use both experimental and computational tools to explore how cells choose their fate, with the ultimate goal of modulating cell state to reshape diseases such as cancer.
SCOUT models gene expression dynamics along single-cell lineage trees using Ornstein-Uhlenbeck processes to distinguish neutral drift from selective pressure, revealing key regulators of metastatic progression.
BASELINE uses Cas12a adenine base editing to irreversibly edit nucleotides within 50 synthetic target sites, recording more than 4,300 bits of lineage information — a 50X increase over existing technologies — and recovering lineage reconstructions up to 40 cell divisions deep.
Using CARLIN lineage recording with single-cell RNA and TCR sequencing, this study reveals that CD8+ T cell clonotypes possess intrinsic TCR-dependent fate biases toward memory or effector development that diverge early during effector differentiation.
SCOUT models gene expression dynamics along single-cell lineage trees using Ornstein-Uhlenbeck processes to distinguish neutral drift from selective pressure, revealing key regulators of metastatic progression.
BASELINE uses Cas12a adenine base editing to irreversibly edit nucleotides within 50 synthetic target sites, recording more than 4,300 bits of lineage information — a 50X increase over existing technologies — and recovering lineage reconstructions up to 40 cell divisions deep.
Using CARLIN lineage recording with single-cell RNA and TCR sequencing, this study reveals that CD8+ T cell clonotypes possess intrinsic TCR-dependent fate biases toward memory or effector development that diverge early during effector differentiation.
Using FLARE, a hierarchical dynamic lineage tracing method, to track AML cell lines through Cytarabine exposure, revealing distinct cellular lineages predisposed to persistence and resistance via upregulation of cell adhesion and motility pathways.
Leveraging loss of heterozygosity events revealed through single-cell RNA sequencing of mouse brain tissue to simultaneously infer developmental lineage and cell type identification.
A high-throughput plasmid sequencing approach using DNA transposition and Oxford Nanopore sequencing. Circuit-seq creates robust, full-length, and accurate plasmid assemblies without prior knowledge of sequences.
Using macsGESTALT, an inducible CRISPR-Cas9-based lineage recorder, to trace metastatic pancreatic cancer and reveal that metastatic potential peaks in rare, late-hybrid EMT states.
A statistical framework for CRISPR barcode lineage estimation using penalized maximum likelihood, enabling inference of relative ordering across parallel lineages.
A developmental single-cell catalog of ~220,000 zebrafish brain cells encompassing 12 stages from embryo to larva, characterizing approximately 800 clusters tracking neuronal and progenitor diversification.
A review of molecular recording methods integrated with single cell profiling technologies, covering recent developments, experimental challenges, computational obstacles, and biological questions.