Research

“After all, it is ongoing work which makes one go to the laboratory with a feeling of suspense and cautious expectation. Although success is rare, we continue in the spirit expressed by Robert Louis Stevenson, that to travel hopefully is better than to arrive.”

-Stephen W. Kuffler

Neuro Lab worker


Overview

We study synaptic alterations and neuronal dysfunctions associated with early stage Alzheimer’s disease, using advanced imaging, cell biology, biochemistry and behavioral techniques in conjunction with transgenic mice and mouse models of Alzheimer’s disease. We are particularly interested in identifying signaling pathways that provide resilience against Alzheimer disease.

Projects

Project 1 focuses on the role of small GTPase, Rab10 in protecting the brain against neurodegeneration, as chronic reduction in the level and activity of this protein reduces the risk of Alzheimer’s disease. Using model mice (J20 and 5xFAD) on Rab10 +/- background, our aim is to identify signaling pathways that mediate Rab10-dependent resilience against Alzheimer’s disease.

Project 2 focuses on the role of a brain specific protein, called ADAP1 (Centaurin α1) in normal brain function and in neurological disorders. Our earlier studies identified ADAP1 as a negative regulator of synaptic plasticity and dendritic spine density. We found that reduction of ADAP1/CentA1 level protects neurons from dendritic spine elimination associated with Alzheimer’s disease. Using mice KO for ADAP1/CentA1 we are dissecting the role of this protein in healthy aging and in neurodegenerative disorders.


Selected Publications

Behavioral and Transcriptome Profiling of Heterozygous Rab10 Knock-Out Mice via PubMed

Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders via Frontiers

CRY-BARs: Versatile light-gated molecular tools for the remodeling of membrane architectures via PubMed

CofActor: A light- and stress-gated optogenetic clustering tool to study disease-associated cytoskeletal dynamics in living cells via PubMed

ADAP1/Centaurin-α1 negatively regulates dendritic spine function and memory formation in the hippocampus via PubMed

Transfection and Activation of CofActor, a Light and Stress Gated Optogenetic Tool, in Primary Hippocampal Neuron Cultures via PubMed

Centaurin-α1-Ras-Elk-1 signaling at mitochondria mediates β-amyloid-induced synaptic dysfunction via PubMed