NIH grant: Functional and mechanistic interrogation of kinase complexes and their ligandability (1R01CA301585-01A1)
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NIH grant 1R01CA301585-01A1: Functional and mechanistic interrogation of kinase complexes and their ligandability
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: Dustin J Maly. Award: $641632.
Start: 2026-08-01T00:00:00.
Abstract
Protein-protein interactions and the assembly of large multi-protein complexes are key components of
biological processes and integral to cellular signaling and their regulatory systems. Our recently developed
approach, kiCCA, studies kinase-protein interactions in native cells and tissue. We identified novel cell-type
specific kinase-protein interactions and dynamic changes in kinase complexes across a panel of 18 cancer cell
lines, identifying potential new regulatory mechanisms for these kinases in specific cellular and tissue contexts.
In this proposal we will use our kiCCA approach to study multiple signaling protein complexes simultaneously
in ten cell signaling pathways across 25 cell lines and in clinical samples of primary liver cancer. We will apply
chemical labeling approaches to profile changes in ligandability of kinase complexes in different cellular
contexts and across timepoints of activation in signaling pathways. We will measure the timing of formation
and dissolution of these kinase complexes to build a database that uniquely identifies these cellular signaling
pathways. These insights are key in understanding redundant signaling networks and the roles they play in
health and disease. We will apply these kinase-protein interactome data in conjunction with kinome profiling to
generate pathway annotation databases to map cell signaling pathways in clinical samples.document fetched 2026-08-09 06:52