Jeffrey D. Rothstein, MD, PhD

Administrative Accomplishments

Dr. Jeffrey D. Rothstein, M.D., Ph.D., is a distinguished leader in neurology and neuroscience, renowned for his extensive contributions to amyotrophic lateral sclerosis (ALS) research and treatment. He serves as the John W. Griffin Director of the Brain Science Institute and is a Professor of Neurology and Neuroscience at Johns Hopkins University School of Medicine. In 2000, Dr. Rothstein founded the Robert Packard Center for ALS Research at Johns Hopkins 25 years ago, where he continues to serve as Director. This center is the first multi-institutional, multi-national collaborative academic organization devoted to understanding the causes of ALS and translating discoveries into new therapeutic approaches. His program oversees and coordinates the leading ALS preclinical researchers worldwide, a team of up to 30 different labs with an annual meeting of more than 450 researchers – academic and commercial in the ALS/FTD space. Dr. Rothstein's leadership extends to his role as the Founder and Executive Director of the Answer ALS Research Program. This initiative combines longitudinal clinical data and induced pluripotent stem (iPS) cell technology to generate comprehensive biological analytics for over 1,000 ALS patients, creating an extensive dataset to advance ALS research with a national team of approximately 100 researchers. He organized and led the first ALS Gordon conference. At Johns Hopkins, his Brain Science Institute, a translational academic unit, has a team of faculty that has coordinated drug development research across the School of Medicine at Hopkins, and that team has spun out more than five new biotech companies over the last 13 years.

Dr. Rothstein's research has been pivotal in identifying foundational defects that cause ALS, including astrocyte dysfunction, excitotoxicity, oligodendroglial injury, and nuclear pore and nuclear transport defects. His work contributed to the successful trials and FDA approval of riluzole for ALS. In recognition of his significant contributions, Dr. Rothstein was elected to the National Academy of Medicine, and the American Association of Physicians both of which represent the highest honors in health and medicine, reflecting his impact on medical science, health care, and public health.

Through these leadership roles and accomplishments working with a wide range of basic and clinical professionals along with training the next generation of neuroscience leaders, Dr. Rothstein has demonstrated a steadfast commitment to advancing basic neuroscience research and translating that commitment to improving patient care in neuromuscular and neurodegenerative diseases.

Degree, Institute, Year Earned

Research Areas

Dr. Jeffrey D. Rothstein's main areas of interest include:

• Amyotrophic Lateral Sclerosis (ALS) Research: Investigating the pathophysiology of ALS, focusing on molecular mechanisms underlying motor neuron degeneration.  
• Nuclear Pore Complex and Nuclear Transport in Neurodegeneration: Examining the biology of the nuclear pore complex and nucleocytoplasmic transport, particularly in relation to TDP-43 loss of function in ALS and other neurodegenerative disorders. 
• Therapeutic Discovery: Developing and testing potential treatments for neurodegenerative diseases, utilizing human induced pluripotent stem cells (iPSCs) platforms and gene therapy/antisense oligonucleotide-based therapies. Currently focussing on the repair of the nuclear pore and restoration of TDP-43 function in ALS, FTD, and Alzheimers disease.
• Glutamate Transporters: Studying the role of astrocytic and neuronal glutamate transporters in neurodegenerative diseases, particularly their function in excitotoxicity and neuronal damage.  
• Astrocyte and Oligodendroglial Biology: Exploring the functions of astrocytes and oligodendrocytes in the central nervous system, including their involvement in synapse regulation and metabolic support of neurons. 

Current Position(s) at Your Current Institution

• Director of the Brain Science Institute, Johns Hopkins University
• Director and Founder, Robert Packard Center for ALS Research at Johns Hopkins
• Professor of Neurology and Neuroscience

Memberships

Service Positions

Editorial Boards:

Other Service Positions:

Science Biography

Dr. Jeffrey D. Rothstein, M.D., Ph.D., is the Johns Griffin distinguished professor of Neurology and Neuroscience at Johns Hopkins University. He serves as the Director of the Brain Science Institute and is the Founder and Director of the Robert Packard Center for ALS Research. He is a clinician scientist combining basic and translational research along with patient care and clinical trials. His research primarily focuses on understanding the molecular mechanisms underlying neurodegenerative diseases, with a particular emphasis on amyotrophic lateral sclerosis (ALS). His work explores several pathways of cellular dysfunction, notably the biology of the nuclear pore, nucleoporins, and nuclear transport in ALS, Huntington's disease, and dementias. Additionally, he has extensively studied the role of astroglia in the central nervous system, investigating their regulatory functions, including glutamate and lactate transporters, and their involvement in both acute and chronic neurodegeneration. A significant aspect of Dr. Rothstein's recent research involves the role of oligodendroglia and their precursors in early neurodegeneration, particularly their function in metabolically supporting axons. His laboratory is notably focused on regulating nuclear transport, monocarboxylate transporter 1 (MCT1) lactate transport, and glutamate transport through drugs that activate transporter transcription, as well as examining nuclear, cytoplasmic, and membrane-interacting proteins that influence transporter processing.  Dr. Rothstein also leads and founded the Answer ALS consortium, a national initiative of 100 investigators that generated over 1,000 ALS and control induced pluripotent stem cell (iPSC) lines. These iPSCs are differentiated into neurons—both cortical and spinal—which were then subjected to extensive multi-omics analyses, including whole genome sequencing, epigenomics, RNA profiling, and proteomics, producing more than 6 billion data points per patient. The entire data set and iPS lines are freely shared to academic and commercial investigators. He founded the Johns Hopkins Robert Packard Center for ALS Research 25 years ago as a collaborative international organization to philanthropically fund ALS preclinical research. Its annual meeting of over 450 ALS researchers is the largest and most advanced ALS research forum responsible for the collaboration of the world's junior and senior ALS researchers. Through these comprehensive research efforts, Dr. Rothstein continues to contribute significantly to the understanding of neurodegenerative diseases, striving to develop novel therapeutic strategies for conditions like ALS.

The full CV for this candidate can be found within the ballot.