Research Interests:
Research Interests:
Research Interests:
Research Interests: Algorithms, Mass Spectrometry, Flow Cytometry, Science, Cytokines, and 18 moreCell Signaling, Multidisciplinary, Hematopoiesis, Signal Transduction, Antibodies, Single cell analysis, Humans, Bone marrow, Phosphorylation, Single Cell, T lymphocytes, DNA content, Immunophenotyping, B Lymphocytes, Thiazoles, Protein Kinase Inhibitors, Bone Marrow Cells, and Cell Size
Research Interests:
Research Interests:
Research Interests:
Research Interests: Algorithms, Flow Cytometry, Multidisciplinary, Nature, Hematopoiesis, and 15 moreHumans, Computer Simulation, Mice, Animals, Bone marrow, Prior Knowledge, Single Cell, Biological systems, Adult, Tumor necrosis factor-alpha, High Dimensionality, Biological markers, Noise Measurement, Spanning Tree, and Bone Marrow Cells
Research Interests:
MYC proteins are major drivers of cancer yet are considered undruggable because their DNA binding domains are composed of two extended alpha helices with no apparent surfaces for small-molecule binding. Proteolytic degradation of MYCN... more
MYC proteins are major drivers of cancer yet are considered undruggable because their DNA binding domains are composed of two extended alpha helices with no apparent surfaces for small-molecule binding. Proteolytic degradation of MYCN protein is regulated in part by a kinase-independent function of Aurora A. We describe a class of inhibitors that disrupts the native conformation of Aurora A and drives the degradation of MYCN protein across MYCN-driven cancers. Comparison of cocrystal structures with structure-activity relationships across multiple inhibitors and chemotypes, coupled with mechanistic studies and biochemical assays, delineates an Aurora A conformation-specific effect on proteolytic degradation of MYCN, rather than simple nanomolar-level inhibition of Aurora A kinase activity.