Biology subjects

De Andrade, V.

Publications and source records attributed to De Andrade, V..

4 recordsLinked to original sources

bioRxiv2026

Cholesterol constrains pore formation by mammalian gasdermins

Pyroptosis is a lytic form of cell death executed by gasdermin pores. Through a CRISPR screen to uncover macrophage genes required for gasdermin D (GSDMD) pore activity, we identify the endosome adaptor Rabgef1 as a positive regulator of pore formation. Rabgef1 deficiency preserves NT-GSDMD membrane binding but prevents NT-GSDMD oligomerization and lytic death. Mechanistic analyses revealed that Rabgef1 deficiency is associated with an overabundance of cholesterol in the plasma membrane. Cholesterol depletion or redistribution through multiple approaches restores GSDMD oligomerization and pyroptosis. The Rabgef1-mediated control of membrane cholesterol and pore formation was found to be a general regulator of the gasdermin family. In cancer cells, organoids, and tumors, cholesterol reduction sensitizes resistant cells to GSDME pyroptosis driven by synthetic mRNAs, chemogenetic induction, and chemotherapy treatment. These results establish membrane cholesterol content as an endogenous checkpoint for gasdermin-mediated pyroptotic cell death during the execution phase, with implications for metabolic disease and cancer immunotherapy.

immunology↗

bioRxiv2023

A Pipeline for a Primate Projectome: mapping every individual myelinated axon across the whole brain

1We developed a pipeline to detail the morphology and complete trajectory of every long distance projecting neuron in large volumes of the non-human primate brain - a projectome. A projectome would organize how the hundreds of brain regions in a primate brain communicate with each other and provide a comprehensive classification of long distance neurons. The reason such projectomes do not exist already is that there is no single imaging technique with the resolution and sampling depth capable of producing one in primates. Here we address that gap by combining new ways to cut brains with minimal tissue loss, nanoscale x-ray microscopy imaging that reveals every individual myelinated axon (MA) and the location, size, and morphology of every neuron, and algorithms for tracing individual myelinated axons for millimeters to centimeters, across tissue gaps.

neuroscience↗

bioRxiv2021

Regional cytoarchitecture of the adult and developing mouse enteric nervous system

The enteric nervous system (ENS) populates the gastrointestinal (GI) tract and controls GI function. In contrast to the central nervous system, macrostructure of the ENS has been largely overlooked. Here, we visually and computationally demonstrate that the ENS is organized in circumferential stripes that regionally differ in development and neuronal composition. This characterization provides a blueprint for future understanding of region-specific GI function and identifying ENS structural correlates of GI disorders.

neuroscience↗

bioRxiv2020

Multi-modal imaging of a single postmortem mouse brain over five orders of magnitude of resolution

Mammalian neurons operate at length scales spanning five orders of magnitude; micron-scale-diameter myelinated axons project millimeters across brain regions, ultimately forming nanometer scale synapses on individual post-synaptic neurons. Capturing these anatomical features across that breadth of scale has required imaging samples with multiple independent imaging modalities (e.g. MRI, electron microscopy, etc.). Translating between the different modalities, however, requires imaging the same brain with each. Here, we imaged the same postmortem mouse brain over five orders of spatial resolution using MRI, whole brain micron-scale synchrotron x-ray tomography (CT), and large volume automated serial electron microscopy. Using this pipeline, we can track individual myelinated axons previously relegated to axon bundles in diffusion tensor MRI or arbitrarily trace neurons and their processes brain-wide and identify individual synapses on them. This pipeline provides both an unprecedented look across a single brains multi-scaled organization as well as a vehicle for studying the brains multi-scale pathologies.

neuroscience↗