E. A. Ortlund

High-throughput screening identifies small molecule inhibitors of thioesterase superfamily member 1: Implications for the management of non-alcoholic fatty liver disease

This study identifies small molecule inhibitors of Them1, showing they enhance fatty acid oxidation and reduce glucose production in liver cells, suggesting therapeutic potential for NAFLD.

Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response

The paper identifies three monoclonal antibodies that poorly neutralize the Omicron BA.1 variant, revealing structural and molecular features of antibody evasion.

Deep mutational scanning identifies SARS-CoV-2 Nucleocapsid escape mutations of currently available rapid antigen tests

APOE Expression and Secretion are Modulated by Mitochondrial Dysfunction

This study shows mitochondrial dysfunction increases APOE expression and secretion in multiple cell types and models, linking mitochondrial health to Alzheimer's disease risk.

Evolutionary tuning of a key helix drove androgen selectivity

The paper investigates how evolutionary changes in helix 10 of androgen receptors drove ligand selectivity by analyzing ancestral proteins and biophysical mechanisms.

Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation

This study shows that glucocorticoid receptor condensates modulate co-regulator recruitment based on DNA-binding sequences, thereby controlling transcriptional activation and repression.

Tapping into a phospholipid-LRH-1 axis yields a powerful anti-inflammatory agent with in vivo activity against colitis

The paper develops a phospholipid-mimicking LRH-1 agonist that shows in vivo efficacy in a colitis model by improving binding affinity and transcriptional activity.

Chemical Systems Biology Reveals Mechanisms of Glucocorticoid Receptor Signaling

The paper uses Ligand Class Analysis to identify target genes and coregulator interactions of glucocorticoid receptor ligands, revealing mechanisms linking ligand structure to physiological outcomes.

Development of a new class of liver receptor homolog-1 (LRH-1) agonists by photoredox conjugate addition

This study develops a new class of LRH-1 agonists using a photoredox conjugate addition method, enabling bridgehead substitution to enhance ligand activation.

Alterations in the human plasma lipidome in response to Tularemia vaccination

This study identifies changes in the plasma lipidome after tularemia vaccination, highlighting key lipid species and their association with inflammation and immune response.

Allosteric regulation of Thioesterase Superfamily Member 1 by free fatty acids and lysophosphatidylcholine

This study identifies the StarD domain of Them1 as a lipid sensor that allosterically regulates its activity and localization in response to fatty acids and lysophosphatidylcholine.

Thioesterase Superfamily Member 1 Undergoes Stimulus-coupled Reorganization to Regulate Metabolism

This paper shows that Them1 undergoes conformational changes in response to stimuli, forming biomolecular condensates that regulate fatty acid oxidation and thermogenesis.

Development of the first low nanomolar Liver Receptor Homolog-1 agonist through structure-guided design

This study develops the first low nanomolar LRH-1 agonist using structure-guided design, showing increased potency and anti-inflammatory effects in an organoid model.