Research expertise of Center Scientists

Jonathan G. Braun     >> homepage
Dr. Braun, Professor and Chair of Pathology and Laboratory Medicine, is a cellular and molecular immunologist whose research is devoted to lymphocyte biology and the identification of genetic traits and their cellular counterparts in immune function. This basic immunologic question is being addressed in the context of several specific diseases. One research focus in his lab concerns the structural basis for recognition of lymphocyte specific pathogens, and the role of host effector mechanisms and its genetic control in autoimmune antigenic mimicry. This project provides a complementary biologic system to study host immune function and genetic regulation in the autoimmune muscle damage associated with Duchenne muscular dystrophy.

Kenneth A. Dorshkind     >> homepage
All blood cells are derived from pluripotent hematopoietic stem cells (PHSC) present in the bone marrow. As PHSC differentiate, they generate progeny committed to the development of either myeloid or lymphoid cells, and it is from these latter progenitors that B and T lymphocytes are ultimately derived. Blood cell production is regulated by systemic signals as well as by a population of bone marrow non-hematopoietic stromal cells that are the source of various growth and differentiation factors. Despite this basic understanding, the precise stages of development between the PHSC and committed lymphoid progenitors remain poorly defined. Accordingly, one goal of my laboratory is to identify immature lymphoid progenitors in bone marrow. A second aim is to define stromal cell and systemic signals that act to regulate the growth and differentiation of these immature lymphoid precursors.

Alan D. Grinnell     >> homepage
Dr. Grinnell, Professor of Physiological Science, is a neuromuscular physiologist whose primary research interest is in the basic mechanisms of neuromuscular synaptic function. Dr. Grinnell's research has long focussed on basic neuromuscular functions in which defects can cause neuromuscular disease. In 1978, he assumed responsibility for initiating the Jerry Lewis Neuromuscular Research Center and its research program at UCLA. His research pursuits that have concerned the role of the immune system in neuromuscular pathology have contributed to current understanding of autoimmune suppression of calcium channel function by serum from patients with Lambert-Eaton myasthenic syndrome (LEMS).

Encarnacion Montecino Rodriguez
Dr. Montecino, Assistant Research Pathologist at the UCLA School of Medicine, has extensive experience in the study of autoimmune pathology in neuromuscular diseases that began with her Ph.D. dissertation work in immunology in Bern, Switzerland. Her work on autoimmune diseases showed that the severity of autoimmune pathology can be significantly altered by different genetic backgrounds and that dysregulation in the development of lymphoid cells can significantly contribute to the severity of these diseases. Dr. Montecino’s expertise in the analysis of early T cell development is proving invaluable in dissecting events in T cell development in dystrophic mice, in particular abnormalities in selection of the T cell repertoire that may predispose to the accumulation of autoimmune T cells with anti-muscle cell specificity.

James G. Tidball     >> homepage
Research in my lab concerns the role of the immune system in promoting or ameliorating muscle pathology during disease or following acute injury. Much of our recent work has focussed on the mdx mouse model of muscular dystrophy, or has involved modications in muscle use that can induce acute injury. We are learning that the immune system plays an important role in regulating the course of muscle injury and repair, in both the chronic disease state or following acute injury. Our ongoing studies are directed to identifying the specific immune cell populations and effector molecules that can promote muscle injury or repair. In our recent work which illustrates our approaches to these problems, we studied dystrophic muscle which contains extraordinarily high levels of myeloid cells, and which lacks nitric oxide synthase (NOS), as a secondary consequence of the dystrophin mutation. We tested whether the loss of NOS from the dystrophic muscle diminished the capacity of muscle to protect against myeloid cell mediated cytolysis by generating a transgenic mouse that lacked dystrophin but produced normal levels of NO. We learned that normalization of NO greatly reduced dystrophic muscle inflammation, muscle membrane lysis and progression of the dystrophic pathology. Our continuing work is directed toward characterizing the mechanisms through which muscle-derived NO decreases inflammation and injury of dystrophic muscle.