Research expertise of Center Scientists
Jonathan G. Braun >>
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
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 >>
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
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.
Montecinos 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 >>
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.