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“Our studies over the past 20 years have increased our understanding of the fundamental processes involved in diseases of aging,” said SIRA director Dennis Carson, M.D., UCSD professor of medicine and a member of the prestigious National Academy of Sciences. “With our new ability to rapidly analyze genes and problems in patients, we can intervene earlier in the disease process.”
plans for the future are to move more and more into clinical applications,
so that diseases of aging can be diagnosed at an even earlier stage,”
“Twenty years ago, researchers were doing their own studies in heart, brain, joint disease and other disorders, without the realization that they were duplicating each others work,” Carson said.
An example was the medical belief that inflammation was primarily associated with rheumatic conditions, such as arthritis. Now, coordinated research among different disciplines has shown that inflammation plays a role in multiple conditions including heart disease, Alzheimer’s and cancer. SIRA investigators have been among the national leaders in this research.
SIRA was born in 1983 when J. Edwin Seegmiller, M.D., UCSD professor of medicine, sought a way to focus the highly respected research expertise of UCSD on diseases of aging. In the 1980s, most academic medical centers were not yet interested in this area, in spite of the vast population of baby boomers about to enter their “older” years.
Formed as an Organized Research Unit, SIRA is a UCSD academic program without walls designed to promote research and collaboration across departments, colleges and campus boundaries. In the laboratory and in clinical research settings, SIRA faculty share resources and knowledge to investigate diseases associated with aging, such as Alzheimer’s disease, cancer, arthritis, osteoporosis, the stress of care giving, glaucoma, macular degeneration, atherosclerosis, late onset schizophrenia, and diabetes.
Over the years, SIRA has awarded numerous faculty grants and student investigator awards. In addition, the organization sponsors free public lectures each month that are later broadcasted on UCSD-TV to a potential viewership of 2.7 million people.
Grants awarded in the Faculty Start-Up Program are designed primarily to assist junior faculty in undertaking innovate research projects, so that they can accumulate the necessary data to apply for larger grants. Each research scientist is awarded up to $10,000. Over the years, 65 grants have been awarded.
One recipient of a faculty grant, Gregg Silverman, M.D., associate professor of medicine, noted that the “seed funds provided by the SIRA grant allowed us to explore new systems and to consider our investigations from an entirely new perspective. In particular, we made our first efforts to consider new therapeutic approaches for rheumatic diseases. Based on the fundamental work supported by SIRA, we were able to submit a successful grant application to the national Arthritis Foundation, which provided a much larger, multi-year grant for the development of new biologic agents for treatment of animal models relevant to clinical lupus and rheumatoid arthritis.”
Another grant recipient, Virginia Waters, Ph.D., Department of Medicine, said that SIRA funding provided her with the opportunity to “demonstrate conjugative gene transfer to mammalian cells. This phenomenon could be more than just very interesting – it could be developed into a safe and efficient gene therapy method.” The results of her work were published in the December 2001 issue of Nature Genetics.
A new SIRA-funded program called the Faculty Collaborative Grant Program began this past summer with the goal of fostering collaboration between researchers from different medical disciplines. The first two $60,000 grants, awarded in July 2003, were presented to the following faculty, to support their innovative research projects related to aging:
Each year, SIRA funds up to five medical students for research in aging during the June to September summer break period. After completing their research, the students participate in the SIRA scientific poster presentation in the spring. Ever since 1989, SIRA has sponsored yearly awards for undergraduate students. Devised to foster interest in age-related research, the program pairs each student with a mentor/researcher to pursue a specific project in aging. Over the years, 90 students have participated in this program.
For more information on SIRA’s public lectures, grants, student investigator program and examples of research, see the website, http://siraucsd.edu and the additional information below.
Among the topics of upcoming lectures in 2003 are:
A Sampling of the Researchers Who Typify SIRA…
Dennis Carson, M.D., is a physician-researcher who studies the abnormalities that cause autoimmune diseases and cancer. Early in his career, he developed the drug 2-chlorodeoxyadenosine, that is highly effective in the treatment of hairy cell leukemia, and other cancers of lymphocytes. Subsequently, he and his colleagues also isolated a defective gene that is involved in about one third of all cancers. In collaborative studies with Eyal Raz, M.D., professor of medicine, Carson determined that microinjection of synthetic DNA, containing particular immunostimulatory sequences, suppresses allergic responses for prolonged periods, without further therapy. These agents are in clinical trials for the treatment of asthma and other allergic diseases.
Dilip V. Jeste, M.D., investigates late-life causes of mental illness and dementia in seniors. He is director of UCSD's Center on Research for Older People with Psychosis, Estelle and Edgar Levi Chair in Aging, professor of psychiatry, and chief, Geriatric Psychiatry Division, UCSD and the VA San Diego Healthcare System. Jeste is also the director of a unique collaborative program between UCSD and the San Diego County Health and Human Services Agency’s Adult and Older Adult Mental Health Services. The program is designed to develop effective new therapies for middle-aged and elderly people with schizophrenia and other psychotic disorders.
Robert M. Kaplan, Ph.D. oversees numerous research programs as chair of UCSD’s Department of Family and Preventive Medicine. Kaplan, whose professional background is in gerontology and geriatrics, is especially interested in ways to get optimal health care treatment given the limited resources available today.
Robert D. Langer, M.D., MPH, is director of the San Diego portion of the national Women’s Health Initiative, which recently reported that combination hormone therapy was potentially more harmful, than helpful for post-menopausal women. He is also the director of a study on vitamin supplements that might prevent prostate cancer in men.
Mahadaven Rajasekaran, Ph.D. is an assistant professor of surgery and director of the UCSD Urology Research Laboratory. He conducts research to determine the causes of male sexual dysfunction. Among his findings to date have been the confirmation that erectile function decreases as age increases and that there is an accumulation of fibrous tissue that loses elasticity in the penis of older experimental animals. He also found a decrease in the levels of neurotransmitters that are responsible for relaxing smooth muscles and a decrease in the levels of some important growth factors that are responsible for blood supply to the penis. Currently, his research team is evaluating whether hormonal supplementation would be beneficial.
Leon Thal, M.D., is chair of the UCSD Department of Neurosciences and director of the national Alzheimer’s Disease Cooperative Study, which recently was awarded a $53 million grant from the National Institute on Aging. Thal studies the potential causes of Alzheimer’s disease, what happens during the course of the disease, and the eventual outcomes. Another area of study involves genetics. He and other investigators have found that there are abnormalities in certain chromosomes that lead to the development of Alzheimer’s at a very early age.
Salvatore Albani, M.D., Ph.D., investigates the role of genetic and environmental factors in the development of rheumatoid arthritis. Currently, a therapy he developed for rheumatoid arthritis is in Phase II clinical trials.
Elizabeth Barrett-Connor, M.D., has studied aging and gender differences, as well as the relation of hormones to cardiovascular disease, diabetes, osteoporosis and cognitive function.
Shu Chien, M.D., Ph.D., director, Whitaker Institute of Biomedical Engineering, studies the effects of mechanical forces on gene expression and signal transduction, biomechanical properties and molecular organization of cell membranes, and much more.
Beatrice Golomb, M.D., Ph.D., focuses on cardiovascular disease and lipids, including a current clinical trial looking at the non-cardiovascular side effects of cholesterol-lowering drugs called statins.
Richard Haas, M.B., is measuring electron transport activities and mitochondrial DNA of platelets obtained from the peripheral blood of Alzheimer’s and Parkinson’s disease patients.
Thomas J. Kipps, M.D., Ph.D., studies vaccines to treat leukemia and rheumatoid arthritis.
Patrick Lyden, M.D., researches new ways to cure and prevent strokes.
Jerrod M. Olefsky, M.D., focuses on the causes and treatment of diabetes, and conducts basic research into the cellular and molecular mechanisms of insulin action.
Andrew L. Ries, M.D., MPH, studies chronic lung diseases that are a common cause of death and disability among seniors.
Paul Sung, Ph.D., investigates the engineering of ligament tissue to replace those damaged beyond repair.
Robert N. Weinreb, M.D., studies all aspects of glaucoma including diagnosis, treatment, molecular genetics and underlying mechanisms.
Examples of Clinical Trials by SIRA Faculty
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