Traditional kinase inhibitors face a trade-off between potency and selectivity because their affinity depends on limited molecular interactions in a single highly conserved binding site. Bitopic inhibitors overcome this limitation by engaging multiple sites on the same target.
Removal of cellular waste from the extracellular space is fundamental for tissue health. Because the rate of material ejected by parenchymal cells varies across tissues, we searched for mechanisms that couple waste production and removal.
Fluorescent imaging in live cells is a cornerstone of life sciences. While natural fluorescent proteins have been engineered to enhance individual features, no existing tag combines ideal properties into a single system: high brightness, reversible binding, compact size, and stability across…
The metabolic importance of brown adipose tissue (BAT) has been recognized, but its origins, particularly supraclavicular BAT (scBAT), remain unclear. Here, we traced scBAT to Mef2c-anterior heart field (AHF)-marked cells. Mef2c-AHF-marked cells isolated from scBAT can spontaneously differentiate…
Fibroblasts adopt diverse cell states in response to inductive cues to maintain tissue homeostasis. We leveraged this cell-state plasticity to define how genome organization contributes to changes in cellular identity. We show that TGF-β reconfigures topologically associating domains and chromatin…
Although biosensors for specific cellular ions are widely available, real-time monitoring of overall ionic strength in living organisms remains challenging. Here, we present a genetically encoded nuclear translocation ionic sensor (GENTIS) that enables direct visualization of ionic stress in vivo.
Saxitoxin (STX) is among the most potent toxins known, is classified as a chemical weapon, and is the archetype of the paralytic shellfish toxin (PST) family produced by marine and freshwater harmful algal blooms (HAB).
Mavacamten is a targeted treatment for hypertrophic cardiomyopathy, a disease caused by genetic variants affecting mainly sarcomeric myosin and its regulator cardiac myosin-binding protein C (cMyBP-C, encoded by MYBPC3). Here we generate knock-in mice including missense pathogenic variant cMyBP-C p…
Oxidative protein folding in the endoplasmic reticulum (ER) is essential for eukaryotic cells yet generates hydrogen peroxide (H2O2), a reactive oxygen species. The ER-transmembrane protein that supports ER proteostasis and guards the cytosol for antioxidant defense remains unidentified. Here, we…
Lipids are integral to ion channel function yet delineating mechanisms by which they affect function remains challenging. Within the K2P family of leak potassium channels, observation of tubular densities interpreted as alkyl chains occupying lateral fenestrations linking the pore and bilayer…
