|
Department of Molecular
and Experimental Medicine
 |
During the last two decades, scientists have begun to understand the molecular basis of disease in terms of
malfunctioning protein and nucleic acid molecules. This has resulted in new
therapies, in particular, small molecule drugs that are specifically directed
at correcting the malfunctioning molecules. However, long before such drugs can
be designed, specific questions need to be answered for each disease:
Where are the malfunctioning molecules? What are their structures? How do they operate? Can we make drugs to
influence them? If so, how do the drugs and the targets interact?
These questions bring together the disciplines of structural biology, cellular biology, catalysis, organic
synthesis, and molecular recognitionÜthe range of disciplines investigated by
researchers in the Department of Molecular and Experimental Medicine (MEM).
With a staff of 50 scientists, the department encompasses a wide range of
specialties and interests.
Since it was formed in the early 1980s, the department has occupied a position at the interface of clinical and
basic research. Uniting the department is the quest to understand the
mechanisms of diseases and to devise strategies to improve health.
Though a number of its members have significant clinical experience, MEM is not a clinical department per
se. Even so, MEM faculty are particularly interested in the clinical applications of their work.
One example is MEM's Division of Experimental Pathology, which tackles hepatitis B, a serious disease caused by
a virus that attacks the liver. More than 350 million people worldwide,
including 1.25 million Americans, suffer from the disease. Hepatitis B is the
leading cause of liver damage and claims more than a million lives a year
worldwide.
The department has become a world leader in the study of hepatitis, especially of the body's immune response to
the disease. The division studies the immunobiology and pathogenesis of
hepatitis B and related viruses in transgenic models and in infected patients.
The Division of Experimental Hemostasis and Thrombosis is attempting to understand blood clots such as those
that cause cardiovascular disease, particularly heart attacks and stroke. One
lab conducts basic research to address the main disease-causing mechanisms
responsible for arterial and venous thrombosis, the clotting of veins and
arteries, and is laying the foundation for novel and more efficient therapeutic
approaches. The investigators study the interaction between vessels and blood
platelets, which are cell fragments that carry the chemicals the body uses in
hemostasis, the process by which blood clots at a site of injury. They are
particularly interested in the structures of the adhesion proteins that mediate
the formation of blood clots and the receptors on the platelets, and they have
been solving the structures of these interacting molecules and piecing together
how they work.
Such detailed knowledge of the three-dimensional structure of these adhesive proteins is indispensable for
understanding the differences between normal hemostasis, where bleeding is
stopped after a cut, and pathological thrombosis, in which a clot of platelets
occludes blood flow and causes cardiovascular disease.
Another serious disease, arthritis, is also of interest in the department. Osteoarthritis is the most common form
of the disease and arises from the degeneration of cartilage in joints. The
Division of Arthritis Research studies cartilage and investigates how one can
influence its growth.
Joint trauma, for instance, is a known risk factor for osteoarthritis, but there are no pharmaceuticals to limit
this tissue damage. Using models of cartilage injury, investigators have found
that apoptosis, or programmed cell death, can be induced by mechanical stress
in joints, and they are testing inhibitors to see whether these can slow
progress to osteoarthritis. The division is also looking at the stimulation of
cartilage damage by chemical signals released by immune system cells and
investigating whether blocking these signals represents a viable approach to
preventing osteoarthritis.
In another line of research with clinical implications, the Division of Hematology has collaborated with Kaiser
Permanente on the largest DNA study in history. This epidemiological study
examined the DNA and clinical data of some 41,000 patients for genetic
susceptibility to a disorder known as hereditary hemochromatosis.
Hemochromatosis is a metabolic disorder in which excess deposits of iron occur
in the liver, pancreas, and other organs. Among other manifestations, cirrhosis
of the liver, diabetes, and cardiovascular disease may result.
Although it was originally thought that most people with the mutation that causes hemochromatosis were symptomatic
and suffered a high mortality rate if not treated, the results of the study
show clearly that few individuals who are genetically predisposed manifest the
disease. Most who are homozygous for this genetic mutation seem to enjoy a
normal life span. This study may lead to a rethinking of the costs and benefits
of screening normal populations for this disease and of the importance of its
early treatment.
MEM also has a basic research division in oncovirology, which seeks to understand the mechanisms by
which genetic changes in growth; regulatory genes lead to the development of
cancer; to investigate signals that control protein synthesis, signals that
control gene expression; to research how other signals cause cancer; and to
apply this knowledge in the development of novel anti-cancer therapies.
Other divisions within MEM include Biochemistry, Biomathematics, Cellular Biology, and Research Rheumatology.
Investigators in the department are also participants in the Scripps Cancer Center with physicians from Scripps
Clinic and the ScrippsHealth system, institutions that together treat 25 to 30
percent of all the cancer patients in the San Diego area. The cancer center's
goal is to facilitate the development of new cancer drugs from their beginnings
in the laboratory to their final approval for use by cancer patients. This
program will enable researchers to contribute more directly to the solutions
they seek by moving potentially useful laboratory findings into the clinic
through their close collaboration with clinical staff.
Top |
About TSRI
Scientific Departments
Centers
Programs
|
