Ravits Laboratory
The Neurogenomics Laboratory at Benaroya Research Center is investigating amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease. ALS is a progressive disease causing paralysis of muscles from degeneration of motor neurons in the central nervous system that control the muscles. The disease begins focally and progresses to contiguous regions of the body. The cause of this degeneration is unknown. In our research, we are combining new biotechnologies to determine which genes in ALS are active that should not be and which genes are inactive that should be. We hope to get clues to determine what processes in the motor neurons are important in their degeneration. If we can identify such critical processes, we might be able to target them for therapy.
Our research begins with a technology called laser capture microdissection (LCM). LCM is a technique that uses infrared lasers through a microscope to isolate and collect specific cells from a histological preparation. We use LCM to collect the motor neurons that are otherwise degenerating and disappearing because of the disease. From the pool of motor neurons, RNA, which carries the expression of genes, is isolated and amplified by a process known as in vitro transcription, which creates hundreds of thousands or even millions of copies of the originals. The amplified RNA is then studied on a computer-controlled system called oligonucleotide microarray. Microarrays are modeled on the computer chip technology and are able to detect signals from thousands of genes and the entire human genome may be profiled. At various steps along the way, we ensure the quality of the RNA on a computerized, electronic bioanalyzer that performs microelectrophoresis.We are currently applying these methods to a human tissue bank that has been specifically created for this research and also to a model of ALS. In the future, we are planning to search for other genomic and viral factors and to investigate other neurodegenerative diseases.
Dr. John Ravits is a clinical neurologist at the Virginia Mason Medical Center and a Clinical Associate Professor of Neurology at the University of Washington. His clinical work has concentrated on neuromuscular diseases especially ALS over the last 19 years and this been the driving force behind the establishment of the neurogenomics laboratory. Dr. Yuxin Fan joined the neurogenomcs laboratory in January 2006 as Staff Scientist. He previously worked at the University of Washington's Center of Neurogenetics and Neurotherapeutics. He trained in clinical neurology before turning to molecular biology to investigate neurologic diseases and has peviously worked on gene regulation, Wilson's disease, and Parkinson's disease. Patrick Laurie has been with the laboratory since its inception. His background is in histology and molecular biology. He has been instrumental in the building of the neurogenomics laboratory and is now one of the most experienced investigators in these technologies and is working full time on these projects.
- Sporadic amyotrophic lateral sclerosis: A hypothesis of persistent (nonlytic) enteroviral infection
- Amyotrophic Lateral Sclerosis Microgenomics
- Focality of upper and lower motor neuron degeneration at the clinical onset of ALS
- Implications of ALS focality: Rostral–caudal distribution of lower motor neuron loss postmortem