Lewis P. Rowland - US grants

This Clinical Research Center, now in Year 21, has been concerned with human neuromuscular diseases. The board objective is to elucidate the etiology and pathogenesis of these disorders, in order to either devise rational treatments for presently untreatable conditions or provide information that could guide sound genetic counseling. The emphasis has shifted in different periods of the grant, but we have concentrated on human patients. The current program includes two main themes: mitochondrial encephalomyopathies and autoimmune motor neuropathies. Center investigators have been active in both fields and have been collaborating for many years. These are three projects. Project 1 Bonilla and Schon will study mtDNA deletions in muscle and brain, using combined morphological and genetic approaches, including novel PCR-based methodologies. Project 2 King and Miranda will study genotype-phenotype relationships of mtDNA mutations in a novel, post-mitotic tissue culture system. Project 3 Latov, Lee, and Hays will study mechanisms by which exposure to Campylobacter jejuni may activate specific 'memory' B cells which recognize the bacterial complex oligosaccharides, resulting in production of pathogenic autoantibodies, using transgenic mouse technology as a key component. A clinical core DiMauro and Rowland will provide direction, administration, external consultation, clinical coordination, and share technical service to the project as a whole. As always, we have encouraged collaboration between the basic and clinical scientists.

The broad objective of this interdisciplinary project is to elucidate the pathogenesis of human neuromuscular diseases. The Center comprises 17 independent investigators in 13 laboratories. In many projects basic scientists and clinical investigators work together. Basic research includes the dynamics of muscle activation and contraction, calcium regulation in muscle, physiology of human muscle fibers, ultrastructure of muscle, development of muscle, muscle culture immunocytochemistry, glycoconjugates, structure and function of acetylcholine receptor. Clinical investigation includes study of muscular dystrophy, myasthenia gravis, malignant hyperthermia, disorders of glycogen and lipid metabolism, hexosaminidase deficiency, and peripheral neuropathy.

The broad objective of this interdisciplinary project is to elucidate the pathogenesis of human neuromuscular diseases. The Center comprises 17 independent investigators in 13 laboratories. In many projects basic scientists and clinical investigators work together. Basic research includes the dynamics of muscle activation and contraction, calcium regulation in muscle, physiology of human muscle fibers, ultrastructure of muscle, development of muscle, muscle culture immunocytochemistry, glycoconjugates, structure and function of acetylcholine receptor. Clinical investigation includes study of muscular dystrophy, myasthenia gravis, malignant hyperthermia, disorders of glycogen and lipid metabolism, hexosaminidase deficiency, and peripheral neuropathy.

neuromuscular disorder; pathologic process; molecular pathology; neurogenetics; clinical research; human subject; genetic techniques; tissue /cell culture;