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A structural perspective on the regulation of the epidermal growth factor receptor.
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a critical role in the pathogenesis of many cancers. The structure of intact forms of this receptor has yet to beExpand
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Small-Molecule Activators of a Proenzyme
Small-Molecule Protease Activator Human proteases regulate numerous biological processes. Most are stored as inactive proenzymes that are activated either by upstream processes or byExpand
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Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate
Bruton's tyrosine kinase (Btk), a Tec-family tyrosine kinase, is essential for B-cell function. We present crystallographic and biochemical analyses of Btk, which together reveal molecular details ofExpand
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Turning enzymes ON with small molecules.
Drug discovery and chemical genetic efforts typically focus on the identification and design of inhibitors or loss-of-function probes as a means to perturb enzyme function. These tools are effectiveExpand
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Crystal Structure of the FLT3 Kinase Domain Bound to the Inhibitor Quizartinib (AC220)
More than 30% of acute myeloid leukemia (AML) patients possess activating mutations in the receptor tyrosine kinase FMS-like tyrosine kinase 3 or FLT3. A small-molecule inhibitor of FLT3 (known asExpand
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Unraveling the mechanism of cell death induced by chemical fibrils
We previously discovered a small-molecule inducer of cell death, named 1541, that non-covalently self-assembles into chemical fibrils (“chemi-fibrils”) and activates procaspase-3 in vitro. We reportExpand
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Self-assembling small molecules form nanofibrils that bind procaspase-3 to promote activation.
Modulating enzyme function with small-molecule activators, as opposed to inhibitors, offers new opportunities for drug discovery and allosteric regulation. We previously identified a compound, calledExpand
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Fibrils Colocalize Caspase-3 with Procaspase-3 to Foster Maturation*
Background: Procaspase-3 is a critical protease in apoptosis. Results: Procaspase-3 has less than 1/10,000,000 the activity of mature caspase-3 and does not detectably autoprocess. Small molecule andExpand
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A structural atlas of kinases inhibited by clinically approved drugs.
The aberrant activation of protein kinases is associated with many human diseases, most notably cancer. Due to this link between kinase deregulation and disease progression, kinases are one of theExpand
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Crystal Structure of the FLT 3 Kinase Domain Bound to the Inhibitor Quizartinib ( AC 220 )
More than 30% of acute myeloid leukemia (AML) patients possess activating mutations in the receptor tyrosine kinase FMS-like tyrosine kinase 3 or FLT3. A small-molecule inhibitor of FLT3 (known asExpand
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