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Rubin Lab

Rubin Lab Research

Summary

Our laboratory is broadly interested in the mechanisms underlying changes in the nervous system as a result of aging or disease, as well as the interactions between the nervous system and the rest of the body that mediate health versus disease. Studies involve a variety of in vivo, in vitro, and in silico approaches to generate insights into the complex molecular pathways underlying different disease states with a goal of identifying novel therapeutic avenues. Current efforts in the lab include studies of the aging brain, CNS disorders (including neuromuscular, neurodegenerative and psychiatric) and skeletal muscle disorders.

Areas of Investigation

Aging of the Brain

Aging is the biggest risk factor for developing late-onset neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease. We are interested in identifying and studying the common biochemical changes that underlie aging and neurodegeneration.

Neuromuscular Disorders

We are developing novel models of neuromuscular disease using patient iPS-derived motor neurons (MNs), and performing high throughput screens to identify compounds that promote MN health and survival. The goal of these studies is to elucidate common molecular mechanisms underlying neuron degeneration and to identify compounds and cellular targets with therapeutic potential.  

Schizophrenia

To start to unravel the connection between the complex genetics and the phenotypes observed in schizophrenia patients, we utilize human iPS cells and small molecule screening assays. We are currently exploring the complement component 4 (C4) gene, which is associated with a high risk of schizophrenia, in stem cell-derived astrocytes and neurons.  

Parkinson’s Disease

We are using dopaminergic neurons derived from Parkinson’s disease (PD) patient iPS cells to model how the genetic differences between individuals confer risk for specific environmental exposures. We are our utilizing the laboratory’s screening expertise to examine dopaminergic neurons with the goal of uncovering new gene-environment interactions in PD.  

Skeletal Muscle

Neuromuscular disorders, such as Spinal Muscular Atrophy (SMA), often comprise a skeletal muscle defect in addition to the problems in the nervous system. SMA patients present with widespread muscle atrophy and weakness. Skeletal muscle tissue is known to regenerate rather well, a capability that is attributed to the activity of satellite cells, the resident skeletal muscle stem cell.  We are carrying out studies to evaluate whether or not defects in satellite cells may contribute to neuromuscular diseases. Our research combines the use of SMA patient-derived iPSCs, genetic mouse models, and phenotypic drug screening methods.

Small Molecule Screening Assays

We have established an extensive range of complex, image-based assays to probe the properties of stem cells and cells derived from them. We use automated, high-content screening imagers, associated robotic equipment, and selected small molecule libraries and combine this high throughput approach with detailed molecular studies to further our understanding of the mechanisms of disease and determine which compounds are most likely to be of therapeutic value.

Join the Rubin Lab

Our lab is recruiting! Interested postdocs are welcome to send a CV and covering letter directly to Lee Rubin.
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