K. Shokat

Selective activation of intracellular β1AR using a spatially restricted antagonist

This paper develops spatially restricted antagonists to selectively inhibit β1AR signaling at the plasma membrane versus intracellular compartments, revealing compartment-specific effects on downstream signaling.

Strain-release alkylation of Asp12 enables mutant selective GTP-state targeting of K-Ras(G12D)

This paper develops covalent inhibitors that target the K-Ras(G12D) mutation by crosslinking aspartate-12 in both GDP- and GTP-states, effectively suppressing cancer cell proliferation and tumor growth.

HBV rewires liver cancer signaling by altering PP2A complexes

This study identifies how HBV alters PP2A complexes to drive liver cancer signaling, revealing potential therapeutic targets.

A reversible SRC-relayed COX2-inflammatory program drives therapeutic resistance in BRAF(V600E) colorectal tumors

This study identifies a SRC-relayed COX2-inflammatory program that drives resistance to BRAF/MEK/EGFR therapies in BRAFV600E colorectal tumors and shows that co-targeting COX2 improves therapeutic outcomes.

Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant

This study identifies that the B.1.1.7 SARS-CoV-2 variant enhances innate immune evasion through increased Orf9b and Orf6 expression and activity.

Phospholipidosis is a shared mechanism underlying the in vitro antiviral activity of many repurposed drugs against SARS-CoV-2

Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant

This study evaluates the efficacy of host-directed therapies against the B.1.1.7 SARS-CoV-2 variant and finds similar antiviral activity compared to early-lineage SARS-CoV-2.

Brain-Restricted mTOR Inhibition with Binary Pharmacology

This paper describes a strategy to achieve brain-restricted mTOR inhibition using a combination of a brain-permeable inhibitor and a brain-impermeable ligand, while preserving systemic mTOR activity.

Bifunctional Small Molecule Ligands of K-Ras Induce Its Association with Immunophilin Proteins

This study designs and characterizes bifunctional ligands that induce K-Ras association with immunophilin proteins, showing their efficacy in blocking B-Raf interaction and suggesting therapeutic potential for Ras-driven cancers.