ABOUT Prof. ASHERY
Graduated from the Hebrew University of Jerusalem, I was always fascinated by the mechanism of neuronal function. Specifically I am interested in understanding synaptic plasticity in normal and disease states. Our lab uses multidisciplinary approaches combining electrophysiology, super-resolution and TIRF microscopy, molecular and cellular neurobiology and computer modeling, to study synaptic plasticity and correlate between molecular changes, synaptic function and dysfunction and animal behavior.
ABOUT The LAB
The Learning and Memory Laboratory, led by Prof. Uri Ashery at Tel Aviv University, investigates how molecular processes at synapses and within neurons shape learning, memory, and neurodegenerative disease. Our work spans fundamental synaptic biology and translational neuroscience, with a particular focus on presynaptic plasticity, Alzheimer's disease, Parkinson's disease and related synucleinopathies, and mitochondrial dysfunction.
We combine electrophysiology with advanced optical imaging, super-resolution microscopy, fast live cell confocal microscopy, genetically encoded sensors and actuators, spatial transcriptomics, proteomics, human iPSC-derived neurons and organoids, animal models, computational image analysis, and behavioral testing. This integration allows us to connect molecular organization at nanometer scales with neuronal activity, circuit function, disease phenotypes, and potential diagnostic or therapeutic applications.
A central theme across our projects is that biological function depends not only on how much of a molecule is present, but also on where it is located, how it is organized, and how it changes over time. By resolving these spatial and temporal dimensions, we aim to identify mechanisms and measurable signatures that can improve the diagnosis and treatment of neurodegenerative disease.
α-Synuclein Structural Biomarkers
We use super-resolution microscopy and computational analysis to define the nanoscale organization of α-synuclein aggregates in skin, cerebrospinal fluid, and brain samples, and to determine whether these signatures distinguish Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. These projects are done in collaboration with Prof. Roy Alcalay, Prof. Sharon Hasson, Prof. Claudio Soto and Prof. Ronald Melki.
α-Synuclein Pathology and Therapeutic Modulation in Cellular Models
We investigate how pathological α-synuclein disrupts neuronal cell biology and how these disease mechanisms can be targeted therapeutically. One arm of the project examines how the A53T α-synuclein mutation remodels stress granules and P-bodies, altering the abundance, nanoscale architecture, three-dimensional organization, and molecular exchange of RNA-binding proteins. A complementary arm uses patient-specific iPSC-derived midbrain organoids carrying LRRK2 G2019S or GBA1 N370S mutations to test GLP-1 receptor agonists and identify genetic and molecular determinants of treatment response. Together, these studies connect α-synuclein pathology with RNA homeostasis and precision therapeutic discovery in Parkinson's disease.
Optical Nanosensors and Targeted Delivery
We develop near-infrared nanosensors together with Prof. Gili Bisker that recognize distinct α-synuclein aggregation states and collaborate on brain-targeted delivery systems designed to transport therapeutic cargo across the blood-brain barrier and into neurons together with Prof. Ben Maoz and Prof. Aviv Schroeder.
cAMP and Mossy-Fiber Plasticity
We investigate how cAMP signals are generated, confined, and decoded at hippocampal mossy-fiber boutons, and how disruption of this organization contributes to impaired synaptic plasticity in Alzheimer's disease. We collaborate with Prof. Shiqiang Gao, who develops cAMP optogenetic probes and with Prof. Haining Zhong, who develops cAMP sensors.
TIMM50 and Mitochondrial Proteostasis
Using patient-derived cells and human iPSC-derived neurons, we study how pathogenic TIMM50 mutations alter mitochondrial protein import, respiration, dynamics, mitophagy, and neuronal electrical activity. We collaborate on that with Prof. Abdussalam Azem and Dr. Yakey Yaffe from The Drimmer-Fischler Family Stem Cell Core Laboratory for Regenerative Medicine https://tauipsccore.sites.tau.ac.il
Durable HBOT for Alzheimer's Disease
We seek to define maintenance schedules that sustain the vascular, synaptic, metabolic, inflammatory, and cognitive benefits of hyperbaric oxygen therapy and identify molecular markers of durable therapeutic response. This project is being done in collaboration with Prof. Shai Efrati and Prof. Shahar Alon.