ANRF 2002-2003 Grant Awards
Long Beach-Based Arthritis National Research Foundation Announces Record Number of Grant Applications

LONG BEACH, Calif., (August , 2002) - Earlier this year, the Arthritis National Research Foundation (ANRF) awarded grants, totaling $583,557, to thirteen scientists investigating how arthritis and various rheumatic diseases occur in the body. As the mechanisms of these diseases are more fully understood, new and better treatments may be developed.
These studies have the potential to benefit millions of Americans suffering with arthritis through the development of new therapies. The immediate benefit is to provide research support for cutting edge projects developed in established laboratories by talented young post-doctoral investigators:

1. Monica Schaller, Ph.D., Scripps Research Institute, La Jolla, CA. Autoantibodies to GPI in Rheumatoid Arthritis Pathogenesis.
Grant Award: $43,557

Dr. Schaller is studying an enzyme present in all cells of the human body, GPI (glucose-6-phosphate isomerase). Preliminary studies indicate that anti-GPI antibodies, found in higher levels in the blood of patients with rheumatoid arthritis, may cause RA. This study will test this hypothesis as well as study GPI in depth in order to facilitate the testing of compounds to block the disease-causing anti-GPI antibodies, hopefully contributing to the reduction or prevention of RA symptoms in humans.

2. Cynthia Benedict, Ph.D., Princeton University.
Elucidating the Mechanism of Receptor Editing: How the Ig Heavy or Light Chain may be Rearranged Secondarily to Avoid Autoreactivity. Grant Award: $45,000

Dr. Benedict’s study centers on the effects of anti-DNA antibodies in systemic lupus erythematosus (SLE or lupus). She will examine genetically engineered mice to study how the immune cells react at the molecular level. The mouse genes have human counterparts and she hopes to use these models to devise strategies for preventing or stopping the damaging effects of anti-DNA production in human lupus patients.

3. Randy Cron, M.D., Ph.D., The Children’s Hospital of Philadelphia – University of Pennsylvania.
Role of NFFAT Proteins in DC154 Gene Regulation and Lupus.
Grant Award: $45,000

Recent findings show that a protein, CD154, is abnormally expressed on the surface of certain white cells of lupus patients. While a therapy blocking the effect of CD154 has improved lupus in mice, it has not had the same effect on humans. Dr. Cron has found that one protein, NFAT, important to the expression of CD154, may be abnormally expressed in humans. They are studying the effect of a new inhibitor of NFAT proteins on CD154 expression in hopes of developing an alternative, potentially less toxic, therapy for lupus patients.

4. Francesca Giannoni, Ph.D., University of California-San Diego. Identification of T cell epitopes that are relevant in the pathogenesis and progression of pediatric SLE.
Grant Award: $45,000

Dr. Giannoni’s project consists of the identification and characterization of the self-proteins thought to cause inflammation in children with lupus. They hope to determine which of these self-proteins trigger the hyper-reactivity of the immune system and their role in the origin of the disease. Molecules derived from these self-proteins could be used in the future for the treatment of lupus.

5. Antonio La Cava, M.D., Ph.D., UCLA.
Characterization of Autoantibody-Reactive T Lymphocytes in Murine Systemic Lupus Erythematosus (SLE).
Grant Award: $45,000

Dr. La Cava will study the characteristics of the cells responsible for the regulation of immune responses in a mouse model that spontaneously develops lupus. The results of this study could identify new markers of intervention and provide new tools for the prevention and therapy of the disease in humans.

6. Alenka Levicnik, M.D., Stanford University School of Medicine. Prevention and treatment of Collagen-Induced Arthritis by adoptive cellular gene therapy.
Grant Award: $45,000

Dr. Levicknik is studying a mouse model of rheumatoid arthritis (RA) similar to human RA. She is attempting a new treatment regimen, adoptive cellular gene therapy. She will test the success of the treatment therapeutically using microarray technology.

7. Harris Perlman, Ph.D., Saint Louis University.
The Role of p21 in regulating IL-6 and MMP in RA
Grant Award: $45,000

Dr. Perlman has identified a gene, p21 that prevents growth and secretion of pro-inflammatory molecules in rheumatoid arthritis. He is studying the pathways of this gene, trying to determine if it is involved in the induction of RA by examining mice lacking the p21 gene. It is hoped that these data will lead to future therapies employing cell growth inhibitors.

8. Kristine Phillips, M.D., Ph.D., Brigham and Women’s Hospital (affiliated with Harvard Medical School).
Role of protein kinase R in TNF-alpha production.
Grant Award: $45,000

Dr. Phillips’ study is evaluating how different levels of TNR-alpha protein are produced. Treatment of arthritis has been revolutionized by the use of biologic agents that inhibit the actions of tumor necrosis factor-alpha (TNF-a) protein. Dr. Phillips’ is seeking to establish the role of the molecules involved in the regulation of TNF-a protein production. Ultimately, the goal is to identify new targets for anti-inflammatory therapies.

9. Alla Tsytsykova, Ph.D., The Center for Blood Research (affiliated with Harvard University).
Inducer-specific TNF-alpha gene regulation in T lymphocytes.
Grant Award: $45,000

This is the second year Dr. Tsytsykova has received funding for her work from ANRF. She is continuing her work studying the process by which the TNF-alpha gene is activated in T lymphocytes (the largest cell population in the synovial fluid of joints). The knowledge gained could lead to new therapies that interrupt TNF-alpha gene expression underlying the onset of rheumatoid arthritis.

10. Craig Walsh, Ph.D., University of California, Irvine.
The role of DRAK2, a lymphoid-enriched apoptotic nuclear DAP-like kinase, in T cell activation and autoimmunity.
Grant award: $45,000

Dr. Walsh’s study is aimed at understanding the basic mechanisms that prevent inappropriate lymphocyte activation in autoimmune diseases, such as rheumatoid arthritis. He has identified a gene, DRAK2, which normally inhibits T cell activation (which causes the inflammatory response). Should this study establish a link between DRAK2 and RA, this gene may serve as a target for clinical intervention.

11. Jian Zhang, M.D., Rush-Presbyterian – St. Luke’s Medical Center, Chicago, IL.
Interleukin-4 Potentiates Peripheral Deletion of Autoreactive Th1 Cells in Proteoglycan-Induced Arthritis.
Grant award: $45,000

Dr. Zhang is studying the mechanism of treating RA with a cytokine called Interleukin-4, which is thought to retard the disease development by inducing apoptosis (death) in harmful T lymphocytes (malfunctioning by attacking self tissues). In normal healthy individuals, the harmful T lymphocytes would be removed by apoptosis, but they remain in RA patients.

12. Mythily Srinivasan, M.D.S., Ph.D., Ohio State University. Immunomodulatory CD28 Peptides in the treatment of Collagen-Induced Arthritis.
Grant award: $45,000

The goals of Dr. Srinivasan’s study are to explore the therapeutic advantages of preventing and improving arthritis through treatment with a synthetic peptide. They will use a mouse model that shares many clinical features of human rheumatoid arthritis and serves as a pre-clinical testing ground for RA.

13. Koichiro Ohmura, M.D., Ph.D., Joslin Diabetes Center (affiliated with Harvard Medical School).
In vivo real time imaging of proteinase activity in arthritis mouse models.
Grant award: $45,000

Dr. Ohmura is perfecting an imaging technology with the potential to greatly benefit the diagnosis of, research on and monitoring the treatment of inflammatory arthritis. He will image the proteinases in the joints of mice with various forms of arthritis. An increase in proteinase activity is one of the initial events of joint destruction in both rheumatoid arthritis and osteoarthritis. This technology may be useful in human disease to image otherwise undetectable or changing levels of cartilage- or bone-threatening increased enzymatic activity.

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