Description:

The Department of Biochemistry & Molecular Genetics presents:

Lindsay Pino, PhD
Co-founder and Chief Technology Officer
Talus Bioscience, Inc.

Presentation: 

Profiling the regulome with high-throughput proteomics to enable small-molecule therapeutics

Abstract:

Transcription factors, cofactors, and chromatin regulators orchestrate gene expression yet remain poorly measured in their native chromatin context and historically difficult to drug. To address these challenges, we developed regulome profiling, a functional proteomics approach that quantifies protein–DNA binding activity in live cells using high-throughput mass spectrometry. This assay measures regulator activity directly, generating proteome-wide maps of DNA engagement that can be compared across perturbations, cell types, and chemical treatments.

Because of its flexibility and high-dimensional output, regulome profiling delivers actionable biological insight across diverse contexts. In deorphanization, we uncover off-target DNA-binding effects of anthracyclines, uncovering new mechanisms of action not previously associated with this drug class. In toxicity studies, regulome signatures reveal early regulatory disruptions preceding transcriptomic or phenotypic changes. In drug discovery, these activity maps expose tractable intervention points directly within disease-relevant cell contexts, seeding a pipeline of small-molecule therapeutics against transcription factors including brachyury (TBXT) and androgen receptor variants.

To accelerate these drug discovery efforts, we built an AI model on top of this unique data, called Strategian. Strategian triages billions of compounds by predicted impact on transcription-factor activity and selectivity, feeding prioritized candidates back into regulome profiling for experimental validation. This closed-loop, two-week iteration connects small-molecule chemistry to chromatin regulatory biology, transforming transcriptional control into a measurable and druggable system.

Host: Dr. Ali Shilatifard, Chairman, Biochemistry and Molecular Genetics; Director, Simpson Querrey Institute for Epigenetics

Refreshments will be served.