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Author

K. Shokat

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Open access Jun 2026

The structural basis for LRRK2’s activation and autoinhibition

Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are the second most common cause of autosomal-dominant Parkinson’s disease (PD), and increased LRRK2 kinase activity is also observed in idiopathic PD, making LRRK2 a major actionable therapeutic target. LRRK2 is a 286-kDa multidomain enzyme containing a Ras-like GTPase...

Amalia Villagran Suarez, Kathryn S. Hatch, Tatyana Bodrug et al. · 1 citation
Open access Sep 2026

Chemical Genetic Targeting of the LRRK2 GTPase Domain

This study utilizes a chemical genetic approach to sensitize LRRK2 to existing GTPase inhibitors and shows that pharmacologically engaging the Roc-COR GTPase domain in cells decreases but does not fully inhibit LRRK2-mediated Rab10 T73 phosphorylation.

Rachel E. Prorok, Lawrence Y. Zhu, Vickie Bowcut et al. · 0 citations
Review Aug 2026

Adaptive mechanisms and emerging cancer therapeutics for CDK2 inhibitors.

The adaptive plasticity of cell-cycle control in cancer cells is discussed and current strategies to target newly emerging CDK2 druggable pockets are highlighted, with an emphasis on chemical biology approaches, aiming to inspire the next generation of CDK2 inhibitors and kinase-targeted therapies more broadly.

Changhao He, K. Shokat · 0 citations
Open access Aug 2026

A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly

BisRoc is identified, a dimeric rocaglate ligand that potently and durably suppresses translation and exhibits greater specificity across a cancer cell line panel than the monomeric RocA.

Jie Liu, Megan K. Moore, Kevin Lou et al. · 0 citations
Open access Aug 2026

The structural basis for LRRK2's activation and autoinhibition.

A unified framework for understanding LRRK2 regulation with broad therapeutic implications is provided, showing that the ROC GTPase governs switching between autoinhibited and active states: GTP binding promotes activation, whereas GDP binding enforces autoinhibition.

Amalia Villagran Suarez, Kathryn S. Hatch, Tatyana Bodrug et al. · 0 citations
Open access Jul 2026

Acute rapamycin treatment reveals distinct mechanisms of dysfunction in a maternal inflammation mouse model

Maternal inflammatory response (MIR) during early mouse gestation induces a cascade of physiological and behavioral changes associated with autism spectrum disorder (ASD). We have shown that mild MIR causes chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth with regionally specific...

Janel Le Belle, M. Condro, C. Cepeda et al. · 0 citations

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