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Chemical Biology Initiative Team

  • lab bottles

    Members of the Chemical Biology Initiative have numerous collaborations with investigators from other Dana-Farber integrative centers, Harvard-affiliated hospitals, and the Broad Institute. Our team includes:

    Nathanael Gray, PhD

    Nathanael Gray, PhD
    Lab Website
    PubMed

    The Gray Laboratory is focused on developing inhibitors for mutant forms of protein kinases often found in cancer. Using kinase-focused libraries designed by structure-guided methods, coupled with kinome-wide selectivity profiling, the Gray lab develops first-in-class chemical inhibitors. They form collaborative teams with cell biologists and translational researchers in the Longwood Medical area and beyond, to further the development of their molecules.

    Michael Eck, MD, PhD

    Michael Eck, MD, PhD
    Lab Website
    PubMed

    Michael Eck and his laboratory employ biochemical and structural methods, including X-ray crystallography to define the molecular interactions that underlie cytoplasmic signal transduction. They are especially interested in determining the structure of signaling complexes that underlie cancer, and in use structural approaches to facilitate development of anti-cancer drugs.

    Active areas of investigation include the structural biology of integrins, focal adhesion kinase (FAK), and Src-family kinases in the regulation of cytoskeletal rearrangements. The Eck Lab also studies the cytoplasmic signaling interactions that control antigen-dependent T-cell activation, and the interactions of the transcription factor Tcf4 with beta-catenin, a driving force in the development of colon cancer.

    Loren Walensky, MD, PhD

    Loren Walensky, MD, PhD
    Lab Website
    PubMed

    The Walensky Laboratory studies deregulated apoptotic and transcriptional pathways in cancer. They develop 'stapled peptides' that preserve the structure of biologically active proteins as chemical probes to target the BCL2 family. Using this approach with structural studies, biochemical and cellular assays they have identified the trigger site on BAX and characterized the activation mechanism of BAK. They are conducting structure-function studies to understand the role BCL2 family member proteins play in chemoresistance.

    Haribabu Arthanari, PhD

    Haribabu Arthanari, PhD
    PubMed

    Protein-Protein Interactions (PPIs) is the Holy Grail of therapeutic intervention, offering a plethora of unique structural landscapes as potential targets. Research in the Arthanari group uses structure-guided approaches to characterize and validate these interactions in the context of disease models. We utilize a combination of techniques including NMR spectroscopy, NMR-based fragment and high throughput screening, and biophysical and cell-based assays to map hotspots in the interaction interface, to further understand the molecular mechanisms orchestrated by these interactions, and to identify disruptive inhibitors that may be developed into treatments for the related pathologies. Current areas of focus include:

    • The critical interactions between transcription factors and the general transcriptional machinery, including the Mediator complex, co-activators, and remodeling factors
    • Translation initiation machinery demonstrated to be dysregulated in cancer
    Sara Buhrlage, PhD

    Sara Buhrlage, PhD
    Lab Website
    PubMed

    Researchers in the Buhrlage group are focused on the development of novel inhibitors and prototype drugs for deubiquitinylases (DUBs). DUBs are involved in the maintenance of protein homeostasis, and several DUB family members have been shown to rescue oncogenic proteins from degradation. The Buhrlage Lab finds new DUB inhibitors, screens them for anti-cancer activity and validates their mechanism of action. They collaborate extensively with biochemists, synthetic chemists, cell biologists, and structural biologists.

    Eric Fischer, PhD

    Eric Fischer, PhD
    Lab Website
    PubMed

    Eric Fischer and his trainees use structural biology, cell biology, and biochemical approaches to investigate the molecular mechanisms of multi-component ubiquitin ligases and their role in cancer. Armed with this knowledge, the Fischer Lab seeks to propose and test new avenues of therapeutic intervention.

    Jun Qi, PhD

    Jun Qi, PhD
    PubMed

    The Qi group designs and synthesizes novel small molecule inhibitors of epigenetic chromatin modification and transcriptional activation, which are dysregulated in cancer. Using a multidisciplinary approach that includes synthetic and medicinal chemistry, chemical biology, and biology, the group seeks understanding of the biological relevance of these epigenetic targets in cancer – with the goal of developing tool and lead compounds to establish rationale for human clinical investigation.

    Justin Kim, PhD

    Justin Kim, PhD

    Lab Website

    Publications

    Research in the Kim laboratory is focused on the development of new chemical tools for chemical biology and total synthesis applications. In particular, the Kim lab explores the development of chemical agents that can be activated specifically in microenvironments unique to tumor cells without interfering with native biochemical processes. The development of these modular, environmentally-responsive components should have far-ranging applications to the development of intracellular probes for imaging and drugs against cancer.