Arthanari Lab
Principal Investigator: Haribabu Arthanari
Institution: Dana-Farber Cancer Institute (Boston, MA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
Abstract Cell cycle checkpoints are essential for maintaining genomic integrity, and their dysregulation is a hallmark of cancer. Among these, the G2-to-M transition is regulated by the kinase WEE1, which delays mitotic entry by phosphorylating and inactivating Cdk1. This modification prevents cell division under conditions of DNA damage or replication stress. Paradoxically, at the G2–M boundary, WEE1 is inactivated through Cyclin-Cdk–mediated phosphorylation to enable cell cycle progression. While WEE1’s opposing roles as kinase and substrate are well recognized, the molecular switch controlling this transition remains poorly understood. This proposal addresses a central, unresolved question in cell cycle biology: how does WEE1 shift between the function of being an enzyme to a substrate? We focus on the underexplored N-terminal intrinsically disordered region (N-IDR) of WEE1, which modulates its kinase activity. Prior structural studies have focused almost exclusively on the kinase domain, typically in inhibitor-bound states, leaving the regulatory N-IDR a mechanistic black box. However, emerging evidence indicates that the N-IDR is essential for full kinase activity and may serv…
Active NIH Awards
- 1R01CA303520-01A1: Flipping the Switch in Cell Cycle Control: Dissecting the Molecular Mechanisms Governing Wee1 Kinase transition from Cdk Inhibitor to Substrate (2026)
- 5R35GM158220-02: Empowering NMR Utilization in Mechanistic Biology: Extending Size Limits and Catalyzing Automation (2026)
- 3R35GM158220-02S1: Empowering NMR Utilization in Mechanistic Biology: Extending Size Limits and Catalyzing Automation (2026)
- 5P01AI143565-07: NMR Core (2026)
- 2P01AI143565-06: NMR Core (2025)
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