J. L. Smith

Substrate Trapping in Polyketide Synthase Thioesterase Domains: Structural Basis for Macrolactone Formation

This study investigates how polyketide synthase thioesterase domains direct substrate nucleophiles for macrolactone formation by analyzing structural and functional properties of modified TEs.

Synthesis of 5-Benzylamino and 5-Alkylamino-substituted Pyrimidoquinoline Derivatives as CSNK2A Inhibitors with Antiviral Activity

The paper synthesizes pyrimidoquinoline derivatives as CSNK2A inhibitors with antiviral activity, finding that certain substituents improve potency while maintaining solubility.

Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3

Chromatin Profiling of CBFA2T3-GLIS2 AMLs Identifies Key Transcription Factor Dependencies and BRG1 Inhibition as a Novel Therapeutic Strategy

This study identifies BRG1 inhibition as a therapeutic strategy for CBFA2T3-GLIS2 AML by analyzing chromatin profiles and CRISPR dependencies.

Optimization of 3-Cyano-7-cyclopropylamino-pyrazolopyrimidines Toward the Development of an In Vivo Chemical Probe for CSNK2

The paper develops analogs of SGC-CK2-1 to improve pharmacokinetic properties in mice by inhibiting GST and P450 enzymes through co-dosing protocols.

Development of Cell Permeable NanoBRET Probes for the Measurement of PLK1 Target Engagement in Live Cells

The paper develops a NanoBRET probe to measure PLK1 target engagement in live cells and evaluates its use with known PLK inhibitors.

A Potent and Selective CDKL5/GSK3 Chemical Probe is Neuroprotective

The paper develops a potent and selective CDKL5/GSK3 chemical probe and demonstrates its neuroprotective effects in human motor neurons under ER stress.

Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development

This study provides the first comprehensive gene expression profile of Plasmodium falciparum liver stages during in vivo development, revealing key metabolic and regulatory processes.

Inhibition of pyrimidine synthesis in murine skin wounds induces a pyoderma gangrenosum-like neutrophilic dermatosis accompanied by spontaneous gut inflammation

This study develops a murine model of pyoderma gangrenosum with concurrent gut inflammation by inhibiting pyrimidine synthesis in skin wounds.

Identification of a chemical probe for lipid kinase phosphatidylinositol-5-phosphate 4-kinase gamma (PI5P4Kγ)

This paper identifies a chemical probe for PI5P4Kγ, demonstrating its selectivity and cellular activity, and shows it activates mTORC1 signaling in breast cancer cells.

Modulation of Tau Tubulin Kinases (TTBK1 and TTBK2) Impacts Ciliogenesis

The paper identifies chemical tools that inhibit TTBK1 and TTBK2, showing that TTBK2 inhibition reduces ciliogenesis in iPSCs.

Host kinase CSNK2 is a target for inhibition of pathogenic β-coronaviruses including SARS-CoV-2

The paper shows that inhibiting the kinase CSNK2 blocks replication of several beta-coronaviruses, including SARS-CoV-2, by preventing viral entry.

Protein proximity networks and functional evaluation of the Casein Kinase 1 γ family reveals unique roles for CK1γ3 in WNT signaling

This study identifies unique roles for CK1γ3 in WNT signaling through proximity biotinylation, functional assays, and inhibitor testing, showing its distinct activation of β-catenin and Notch pathways.

Multiple mechanisms for overcoming lethal over-initiation of DNA replication

The paper identifies multiple mechanisms by which cells regulate DNA replication in Bacillus subtilis, including reducing initiation and enhancing elongation to overcome over-initiation caused by dnaA1 mutation.

Beneficial and detrimental genes in the cellular response to replication arrest

This study identifies genes affecting survival during replication arrest in B. subtilis, finding that RecJ promotes cell death while AddA supports survival through RecA assembly differences.

Myeloid Lineage Enhancers Drive Oncogene Synergy in CEBPA/CSF3R Mutant Acute Myeloid Leukemia

The paper identifies mutation synergy between CSF3R and CEBPA in AML, showing their interaction at myeloid lineage enhancers and the requirement of CEBPA mutations as an initial event.

FLASH: A next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences

FLASH is a CRISPR-based diagnostic method that enhances detection of low-abundance antimicrobial resistance sequences in metagenomic data.

Structural basis of the Cope rearrangement and C-C bond-forming cascade in hapalindole/fischerindole biogenesis

This paper reports the structure of HpiC1, a Stig cyclase involved in hapalindole/fischerindole biosynthesis, revealing its dimeric assembly and key residues for catalytic steps.