A graduate of Yale University, Dr. Ravits earned his MD from the Mayo Clinic School of Medicine and completed his internship and residency in neurology at UC San Diego. He then did fellowships in neurophysiology and neuromuscular diseases: one year at the Brigham and Women’s Hospital, Harvard Medical School, and two years at the National Institute of Neurological Diseases and Stroke, National Institutes of Health.
In 1986 he joined the medical staff of Virginia Mason Medical Center in Seattle, specializing in neuromuscular disorders and neurophysiology. He served as Director of their Clinical Neurophysiology Laboratory and, for several years, as Head of the Section of Neurology. In 2004, he started a translational research program at the Benaroya Research Institute at Virginia Mason to focus on research of amyotrophic lateral sclerosis (ALS or “Lou Gehrig’s disease”).
Dr. Ravits has three board certifications from the American Board of Psychiatry and Neurology: Neurology, Neuromuscular Medicine and Clinical Neurophysiology. He is also boarded by the American Board of Electrodiagnostic Medicine. He is a Fellow of the American Academy of Neurology and of the American Association of Neuromuscular and Electrodiagnostic Medicine, and a member-elect of the American Neurological Association (2011).
He is on the Editorial Board of Amyotrophic Lateral Sclerosis, the Scientific Advisory Committee of the Muscular Dystrophy Association, and the steering committee of the Research Committee on Motor Neuron Diseases of the World Federation of Neurology. He is Co-Chairman of the Western ALS Study Group (WALS) and a member of the Northeast ALS Study Group.
Dr. Ravits has been a co-investigator for several ALS clinical trials. He is an ad hoc journal reviewer for Muscle & Nerve, Journal of Clinical Neurophysiology, Journal of Neurological Sciences and Acta Neurological Scandinavia. He is an ad hoc scientific grant reviewer for the ALS Society of Canada, the UK Motor Neurone Disease Association, the French Thierry Latran Foundation, and the Italian AriSLA.
Dr. Ravits’ primary clinical interests are ALS, motor neuron diseases, neuromuscular disorders and clinical neurophysiology. Through his clinical work, he observed the clinical onset and progression of ALS and thus formulated a hypothesis providing a unifying explanation of fundamental disease mechanisms. In brief, the hypothesis is that degeneration is a focal process that spreads contiguously outward anatomically over time. This phenomenon is most clearly seen early in the disease before complexity is caused by temporal-spatial summation. This suggests a key property of the disease is 3-dimensional propagation—neuronal degeneration is over space as well as time.
Between 2007 and 2009, he published a series of three papers in the journal Neurology presenting this information and over the past five years he gave many national and international presentations about it. In 2011, he moved to UCSD to head the newly forming translational research program in ALS and to team with the world class scientists at the university (see http://als.ucsd.edu).
Dr. Ravits’ research is translational research of ALS seeking to understand disease mechanisms by profiling RNA through a process of discovery and in turn to seek rationally based targets for therapy. The studies are timely in light of the growing appreciation of the importance of RNA processing in ALS. The research is doing this by exploiting the focal spread of disease to apply technologies directly to less degenerated regions in the nervous systems. These technologies include laser capture microdissection, RNA amplification, microelectrophoresis, microarray, and currently RNA-seq.
Several years were spent establishing a repository of nervous systems and validating the RNA quality. The first studies profiled 3 ́gene expression, exon splicing, and microRNAs and current studies are profiling coding and non-coding RNA using RNA-seq. For the computational analysis of the genome-scale data, he is working with and supported by collaborators at the Microsoft Research (Microsoft’s research division ) as well as collaborators at UCSD. He has recently reported in Human Molecular
Genetics three main observations from the first wave of transcriptional studies:
- Key biological signals are compartment-specific, strongest in the pool of motor neurons isolated by laser microdissection and weak in the surrounding anterior horn microenvironment;
- Abnormalities of exon splicing are more significant than abnormalities of differential gene expression and are more up-regulated than down-regulated (consistent with an active energy-dependent pathological process);
- Aberrantly spliced genes are highly enriched in cell-matrix adhesion biology, suggesting the attachment and communication of the motor neuron to its microenvironment plays an important role in molecular pathogenesis (and interesting in view of our beliefs about pathological spread).
Another aspect of his research is in vitro models of propagation, pursuing a variety of experiments in 2- and 3-dimensional cell culture with human motor neuron-like cells called HSP1 cells to seek to model and study cell-cell and cell-matrix interactions for models of propagation.