chemical-biology-lab-2024

Chemical Biology Program Research

We combine chemical biology, structural and mechanistic insights, proteomics, protein engineering, and design to tackle tough problems at the forefront of cancer research. 

Our Mission

To use the power of chemical biology and mechanistic understanding of biological processes to transform the way we study and target disease, especially cancer

Featured Studies

REVIEW: Signaling from RAS to RAF: The Molecules and Their Mechanisms

Researcher: Michael Eck, PhD | Eck Lab

The RAS/RAF/MAP kinase pathway is one of the most critical signaling cascades in cells. It controls cellular proliferation, differentiation, and survival in response to external signals, and its dysfunction is linked to many malignancies. Over the past few years, structural and biochemical studies have provided new understanding of RAF autoregulation and activation, and this review discusses these advances and their implications for cancer drug discovery and development.

READ DR. ECK’S FREE REVIEW



PREPRINT: Unveiling the Hidden Interactome of CRBN Molecular Glues With Chemoproteomics

Researcher: Eric Fischer, PhD | Fischer Lab

Researchers from the Fischer Lab established a high throughput affinity purification mass spectrometry-based workflow for unbiased identification of molecular glue targets. Using this strategy, they identified close to 300 targets of 20 CRBN-binding molecular glues.

READ DR. FISCHER's paper



Group 3 Medulloblastoma Transcriptional Networks Collapse Under Domain Specific EP300/CBP Inhibition

Researcher: Jun Qi, PhD | Qi Lab

Here, Qi lab, in a collaborative effort, discovered that targeting different domains of EP300/CBP has different effects in different cancers. For example, in G3MB using inhibitors that target the bromodomain (BRD) caused rapid disruption of genetic dependency networks that are required for tumor growth, unlike inhibitors that target another domain called HAT. This study provides important evidence that targeting different domains of multidomain proteins yields different phenotypes, something that has thus far been overlooked in drug discovery.

READ DR. QI's paper

Explore More of Our Research Interests

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Research Spotlight

Fischer Lab, in collaboration with colleagues from the Broad Institute, developed the next-generation of degron tags that can be engineered into target proteins to induce their controlled degradation. The tag developed here is a short zinc-finger degron that engages the cereblon, only in the presence of small molecule ligands that induce binding between the tag and cereblon. In this manner, the tag + small molecule serve to glue the protein of interest to an E3 ligase machinery that results in target ubiquitination and degradation.

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