Theodore L. Roth

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits

Genome-scale CRISPRi perturb-seq in 22 million primary human CD4+ T cells maps stimulation-specific regulators and links perturbation signatures to T cell states and autoimmune genetics.

Toxicity of extracellular cGAMP and its analogs to T cells is due to SLC7A1-mediated import

The paper identifies SLC7A1 as the transporter for cGAMP and its analogs in T cells, showing that targeting this transporter can reduce toxicity without affecting arginine transport.

Stack: In-Context Learning of Single-Cell Biology

SO_SCPLOWTACKC_SCPLOW is a foundation model trained on human single-cell data that enables in-context learning for predicting perturbation effects without fine-tuning.

Ultra-large targeted DNA integrations in primary human cells

This paper identifies methods to achieve ultra-large DNA integrations (>10 kb) in human cells with high efficiency using optimized templates and delivery strategies.

Systematic identification of seed-driven off-target effects in Perturb-seq experiments

The paper identifies off-target effects in CRISPRi Perturb-seq experiments by analyzing transcriptional similarity between on-target and off-target guide effects.

Molecular pixelation of the CAR T cell surface proteome

The paper uses Molecular Pixelation to analyze surface proteomic signatures of CAR T cells under acute and chronic stimulation, identifying spatial patterns linked to exhaustion.

A unified genetic perturbation language for human cellular programming

CRISPR-All enables genome-scale, combinatorial genetic perturbations in human cells, revealing additive functional improvements through multiplexed modifications.

Mitochondria redistribution organizes the immunosuppressive tumor ecosystem

The paper shows cancer cells redistribute mitochondria to sustain immunosuppressive ecosystems, reprogramming immune cells and enhancing their own metabolic resilience.

Site-specific DNA insertion into the human genome with engineered recombinases

This study engineers recombinases to improve DNA insertion efficiency and specificity in human cells, achieving 53% integration and 97% genome-wide specificity.

Scalable transcription factor mapping uncovers the regulatory dynamics of natural and synthetic transcription factors in human T cell states

The paper develops and applies a scalable method to map transcription factor binding in human T cells, revealing novel regulatory dynamics and gene targets.

Immune Composition of the Mononuclear Cell Fraction of Human Umbilical Cord Blood

This study characterizes the immune subset composition of umbilical cord blood mononuclear cells and compares them to adult peripheral blood, revealing distinct immune profiles and developmental trends.

Evolutionarily guided transcription factor design programs novel T cell states

This paper designs novel transcription factors using evolutionary principles to generate T cell states with enhanced functionality.

Robust T cell activation requires an eIF3-driven burst in T cell receptor translation

This study identifies eIF3's role in regulating TCR translation via 3-UTR binding, enhancing CAR-T cell efficacy in vitro.

Hybrid ssDNA repair templates enable high yield genome engineering in primary cells for disease modeling and cell therapy manufacturing

The paper develops a non-viral method using hybrid ssDNA repair templates to improve genome engineering in primary human cells, achieving high knock-in efficiency and cell yields for disease modeling and cell therapy.

Efficient Generation of Isogenic Primary Human Myeloid Cells using CRISPR-Cas9 Ribonucleoproteins

This paper describes a method to efficiently generate genetically modified primary human myeloid cells using CRISPR-Cas9 RNP nucleofection, demonstrating its utility in studying HIV-1 infection and myeloid cell biology.

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

Affinity-purification mass spectrometry of 26 SARS-CoV-2 proteins in HEK293T cells yields 332 high-confidence host interactions and 67 druggable human proteins with known compounds.

A burst in T cell receptor translation mediated by eIF3 interactions with T cell receptor mRNAs

The paper identifies eIF3's role in enhancing TCR translation during T cell activation through interactions with 3-UTRs of TCR mRNAs.

Reprogramming human T cell function and specificity with non-viral genome targeting

This paper develops a non-viral CRISPR-Cas9 system for precise genome editing in human T cells, enabling therapeutic reprogramming of cell function and specificity.

A CRISPR-Cas9 Genome Engineering Platform in Primary CD4+ T Cells for the Interrogation of HIV Host Factors

The paper describes a CRISPR-Cas9 platform for editing primary CD4+ T cells to study HIV host factors, enabling high-throughput gene manipulation and downstream analysis.

Discovery of an autoimmunity-associated IL2RA enhancer by unbiased targeting of transcriptional activation

The paper identifies an IL2RA enhancer associated with autoimmunity using CRISPRa and shows it affects gene activation timing without blocking expression.