Paddison Lab
Principal Investigator: Patrick Paddison
Institution: Fred Hutch Cancer Center (Seattle, WA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
SUMMARY Kinetochores (KTs) are large protein structures assembled upon centromeres during mitosis that bind to microtubules (MTs) of the mitotic spindle to orchestrate and power chromosome movements. We have recently discovered that a high proportion of human glioblastoma isolates suffer from a lethal form of KT stress, which is triggered by oncogenic mitogen-activated protein kinase signaling [Mapk stressed KTs (MaSKs)]. MaSKs arise when the Ras-Raf-MEK-ERK cascade is inappropriately active in mitosis, resulting in hyperstimulation of a network of KT kinases that, in turn, hyperphosphorylate KTs, decreasing their MT binding capacity and causing excessive KT-MT turnover. The purpose of this grant is to reveal mechanistic details of our MaSK model while revealing MaSK relevance to KT and cancer biology. Our overarching hypothesis is that oncogenic RTK-Ras-Raf-MEK-ERK signaling alters the activity of key proteins involved in KT regulation causing cancer-specific destabilization of KT-MT attachments and requirement for MaSK-associated compensatory mechanisms. Aim 1 will investigate the nature, function, and regulation of MaSKs in glioblastoma isolates. Aim 2 will reveal the occurrence…
Active NIH Awards
- 5R01CA295090-02: MAPK-driven kinetochore stress in cancer (2026)
- 1R01CA295090-01A1: MAPK-driven kinetochore stress in cancer (2025)
- 5R01NS119650-06: Defining cellular states of quiescence in human brain tumors (2025)
- 5R01NS119650-05: Defining cellular states of quiescence in human brain tumors (2024)
Explore 700+ US Biology Labs on FindBioLabs.com