Jeffrey Rothstein

Jeffrey Rothstein, MD, PhD, is a Professor of Neurology and Neuroscience at Johns Hopkins University and Director of the Brain Science Institute. His research focuses on the molecular and cellular mechanisms underlying neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS). Dr. Rothstein leads the Answer ALS consortium, a national initiative generating multi-omics data from induced pluripotent stem cell (iPSC) lines derived from ALS patients and controls. His work investigates astroglial biology, glutamate transporters, nuclear pore dysfunction, and oligodendroglial metabolic support in neurodegeneration.

Research interests include: nuclear transport mechanisms in ALS/FTD, glial cell dysfunction, and iPSC-based disease modeling. He has pioneered studies on glutamate transporter regulation, astrocyte subtypes, and the role of MCT1 lactate transport in neurodegeneration. His laboratory combines genetic models, high-throughput screening, and advanced omics technologies to identify therapeutic targets.

Key contributions include: defining astrocyte roles in synaptic regulation, identifying nuclear pore complex injury in ALS, and developing iPSC-derived motor neuron models for disease analysis. Ongoing projects focus on drug discovery targeting glutamate transport activation and nuclear transport pathways, leveraging transgenic mouse models and viral vector therapies.

Lab activities encompass: iPSC differentiation protocols, CRISPR-based gene editing, and analysis of metabolic interactions between neurons and glia. Collaborations with clinical teams enable translational research bridging basic science discoveries to clinical trials.