S. Knapp

Nuclear receptor corepressor 1 controls regulatory T cell subset differentiation and effector function

This study shows NCOR1 regulates Treg cell differentiation and suppressive function by maintaining transcriptional integrity in both naive and effector states.

Functional characterization of pathway inhibitors for the ubiquitin-proteasome system (UPS) as tool compounds for CRBN and VHL-mediated targeted protein degradation

The paper evaluates diverse ubiquitin pathway inhibitors as controls for CRBN and VHL-mediated protein degradation, assessing their potency and toxicity using the HiBiT system and high content assays.

Synthesis and evaluation of chemical linchpins for highly selective CK2α targeting

The paper designs and evaluates chemical linchpins targeting CK2α with a novel binding mode combining allosteric and ATP competitive elements, showing high selectivity and low micromolar activity.

Convergent evolution of plant prickles is drivenby repeated gene co-option over deep time

The paper investigates convergent evolution of plant prickles, finding that mutations in a cytokinin gene repeatedly cause prickle loss across species.

Back-pocket optimization of 2-aminopyrimidine-based macrocycles leads to potent dual EPHA2/GAK kinase inhibitors with antiviral activity

The paper optimizes a 2-aminopyrimidine-based macrocycle to create a dual EPHA2/GAK kinase inhibitor with antiviral activity against dengue virus.

Thermodynamic Characterization of LC3/GABARAP Ligands byIsothermal Titration Calorimetry

This paper provides a detailed protocol for producing LIR peptides and using ITC to study their interactions with LC3/GABARAP proteins, including troubleshooting guidance.

Development of selective pyridopyrimidin-7(8H)-one-based Mammalian STE20-like (MST3/4) kinase inhibitors

This study develops selective MST3/4 kinase inhibitors and demonstrates their distinct cellular effects compared to MST1/2 inhibition.

Development of LRRK2 designed ankyrin-repeat proteins

This study develops a high-affinity DARPin that binds to LRRK2's WD40 domain, improving structural analysis and revealing its role in disrupting LRRK2 filaments and Rab8A phosphorylation.

Discovery of the sEH Inhibitor Epoxykynin as Potent Kynurenine Pathway Modulator

The paper identifies epoxykynin as a potent sEH inhibitor that modulates the kynurenine pathway, offering new opportunities to address cancer-induced immune tolerance.

Synthesis of pyrazole-based macrocycles leads to a highly selective inhibitor for MST3

The paper designs and synthesizes a macrocyclic inhibitor, JA310, that selectively targets MST3 with high potency and kinome-wide selectivity.

Targeting LC3/GABARAP for degrader development and autophagy modulation

The paper evaluates the druggability of LC3/GABARAP for autophagy modulators and identifies ligands that bind to the HP2 pocket of the LIR docking site.

Discovery of a new activator of Slack potassium channels with robust efficacy in models of histamine-independent and chronic itch

This study identifies compound 6 as a potent Slack potassium channel activator effective in treating histamine-independent and chronic itch without motor side effects.

Inhibition of Parkinsons Disease-related LRRK2 by type-I and type-II kinase inhibitors: activity and structures

This study presents cryo-EM structures of LRRK2 bound to type-I and type-II inhibitors, revealing conformational changes and providing a basis for inhibitor design.

Development of potent dual BET/HDAC inhibitors via pharmacophore merging and structure-guided optimization

This study develops potent dual BET/HDAC inhibitors through pharmacophore merging and structure-guided optimization, showing improved potency and efficacy in cancer cell models.

Urbanisation generates multiple trait syndromes for terrestrial taxa worldwide

This study shows urbanisation causes taxon-specific trait changes in terrestrial species, with reproductive and dietary traits most affected, and identifies four general urban trait syndromes.

TREM2 limits necrotic core formation during atherogenesis by controlling macrophage survival and efferocytosis

This study shows TREM2 deficiency increases necrotic core formation in atherosclerosis by impairing macrophage efferocytosis and survival.

Shifting the selectivity of pyridopyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily

This paper develops a selective SIK kinase inhibitor, MR22, by optimizing a pyrido[2,3-d]pyrimidin-7(8H)-one scaffold to eliminate PAK activity, demonstrating its efficacy in ovarian cancer cells.

5-iodotubercidin sensitizes cells to RIPK1-dependent necroptosis by interfering with NFkappaB signaling

This study identifies 5-iodotubercidin as a compound that sensitizes cells to RIPK1-dependent necroptosis by inhibiting NFκB signaling in MK2-deficient cells.

Morphological trait evolution in Solanum (Solanaceae): evolutionary lability of key taxonomic characters

This study maps the evolution of 25 morphological traits across Solanum species, revealing high lability in traits like growth form and glandular trichomes, and identifying convergent traits useful for classification.

Mast cell-derived BH4 is a critical mediator of postoperative pain

This study identifies mast cell-derived BH4 as a key mediator of postoperative pain, showing that substance P triggers BH4-dependent serotonin release in mast cells, and blocking substance P reduces pain.

Death by a Thousand Cuts -- Combining Kinase Inhibitors for Selective Target Inhibition and Rational Polypharmacology

This paper presents a method to improve kinase inhibitor selectivity by combining inhibitors with divergent off-target activities, validated using a NanoBRET assay.

SGC-CLK-1 (CAF-170) a chemical probe for the Cdc2-Like kinases CLK1, CLK2, and CLK4

This paper identifies and characterizes SGC-CLK-1, a potent inhibitor of CLK1, CLK2, and CLK4, showing its selectivity and effects on SR protein phosphorylation and localization.

A novel role for cystathionine gamma lyase in the control of p53: impact on endothelial senescence and metabolic reprograming

This paper identifies CSE-p53 interaction as a regulator of endothelial cell senescence and metabolic reprogramming in aging, showing that restoring this interaction can prevent senescence and promote vascular repair.

PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain

This study identifies that PKC isoforms activate LRRK1 by phosphorylating specific residues in the CORB GTPase domain, enhancing kinase activity.

Projecting the futures of plant traits across habitats in Central Europe

The paper projects future changes in plant traits for native and non-native species under environmental scenarios in Central Europe.

A neutrophil-B-cell axis governs disease tolerance during sepsis via Cxcr4

This study identifies a neutrophil-B-cell axis that promotes disease tolerance during sepsis through Cxcr4 activation, reducing organ damage and immunothrombosis.

Two helices control the dynamic crosstalk between the catalytic domains of LRRK2

The paper identifies two helices that regulate the conformation and function of the kinase domain in LRRK2 through dynamic crosstalk.

Development of a novel, pan-variant aerosol intervention for COVID-19

This paper reports preclinical development and evaluation of aerosolized soluble recombinant human ACE2 (APN01) as a COVID-19 intervention.

Nanobodies as allosteric modulators of Parkinson's disease-associated LRRK2

This study identifies and characterizes Nanobodies that modulate LRRK2 activity through non-ATP-competitive mechanisms, offering new tools for Parkinson's disease research and therapy.

ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology

This paper develops a mouse-adapted SARS-CoV-2 strain, maVie16, to model COVID-19 in mice, showing that ACE2 is critical for disease and that blocking TNF/IFNγ reduces immunopathology.