S.L.E. Lupus Foundation Awards Six More New Investigator Grants

Additions Fortify Pool of Scientific Talent in Lupus

New York, NY, July 2006 - The S.L.E. Lupus Foundation, in a reinforcement of its long standing as the nation's largest initiative dedicated to nurturing new scientific talent in lupus research, has raised its current financial commitment to nearly $3 million with the award of six more New Investigator Program grants.

"By giving financial support and expert guidance to researchers early in their careers and enabling them to pursue their interest in lupus and autoimmunity, we ensure that good ideas are continually brought to the table and our brightest new scientists are able to stay engaged in finding answers to this complex and difficult disease," said Foundation Executive Director Margaret G. Dowd.

In the latest round of grant applications, the Foundation received more solid proposals than ever since launching its research program nearly 30 years ago, and from scientists at some of the leading lupus laboratories in the New York Regional area.

Enthusiasm for lupus research was clearly evident in the applications, reviewers reported. "The S.L.E. Foundation is facilitating opportunities for young investigators to bring their skills to lupus research" said Jill Buyon, M.D. "Researchers are purposefully seeking funding from the Foundation because they are truly excited about studying lupus."

The Clinician-Scientist Fellowship Awards ($150,000 over 3 years) were given to the three investigators who demonstrated a particularly strong commitment to lupus research and great potential for going on to an independent investigative career.

Peter Izmirly, M.D. at NYU—Hospital for Joint Diseases will detail the steps that lead to damage of blood vessel linings ("endothelium") in lupus, and in the kidneys in particular. With the goal of gaining a fuller understanding of how blood vessel damage contributes to kidney disease, Dr. Izmirly will perform the clinical evaluation of individuals with lupus, and in the laboratory search for biomarkers and genetic clues to damage using blood and urine samples. "This is a stellar example of a human translational research project," said reviewer Dr. Buyon, that effectively merges laboratory research with patient care. Dr. Izmirly will work with mentor Robert M. Clancy, M.D.

Mikhail Olferiev, M.D. at Cornell University/Hospital for Special Surgery will look at a product formed in the blood circulation when antibodies meet their targets—potentially damaging immune system "complexes" that can cause vast inflammation and subsequent tissue damage. Researching in test tubes, he will examine various molecules that direct cells with "headlights" called FcyR receptors to either rid the body of these potentially damaging complexes or allow them to stay and cause inflammation and tissue damage. The hope is to uncover strategies for modulating FcyR-mediated inflammation in lupus. Dr. Olferiev will work with mentor Luminita Pricop, M.D.

Carolina Llanos, M.D., Ph.D. at NYU—Hospital for Joint Diseases will study how a pregnant woman's anti-SSA/Ro-SSB/La autoantibodies can cause a condition in which the fetal heart beats abnormally slowly. The 40 percent of women with lupus who have these antibodies run a 2 percent risk of bearing a child with this serious and potentially fatal complication called congenital heart block (CHB). Dr. Llanos hypothesizes that binding of the woman's anti-SSA/Ro and or SSB/La antibodies to apoptotic (programmed to self-destruct) cardiac cells leads to their impaired clearance, a factor which may then promote an inflammatory cascade that results in CHB. Understanding these steps through test tube studies will advance the study of CHB as well as provide insight into how antibodies cause injury to organs overall. Dr. Llanos will work with mentor Jill Buyon, M.D.

Basic Science Fellowship Grants ($135,000 over 3 years) were given to three investigators based on the high quality of the proposed training program as well as qualifications similar to those for Clinician-Scientist Fellowship Awards.

Qinzhong Chen, Ph.D., at Columbia University will work with mentor Alessandra Pernis, M.D. to address a central question in lupus—why T cells of the immune system fail to be controlled and regulated as they should. Using preliminary findings of a novel molecule in T cells called IBP, Dr. Chen will examine the mechanism by which IBP controls the function and activation of T cells. Interestingly, mice without this molecule develop a lupus-like disease. Better understanding of IBP's role in T cells could point the way toward new treatment strategies.

Joel Cohen-Solal, Ph.D. at Columbia University will work with mentor Betty Diamond, M.D., to explore why some women with lupus have disease flares and complications when taking estrogens (oral contraceptives, hormone replacement therapy), while others do not. Does this disparity reflect a genetically determined response to estrogen on the part of the immune system's antibody-producing B cells? Understanding the role of estrogen on B cells in two genetically different strains of mice could lead to urgently needed answers on which women with lupus can safely take estrogens, as well as illuminate molecular targets for therapy.

Ramalingam Bethunaickan, Ph.D. at Columbia University will work with mentor Anne Davidson, M.D., to determine how two types of lupus kidney disease—one with excessive inflammation and one with predominant scarring—respond to a combination of standard and relatively new medications. (Test medications include intraveneous cytoxan, mycophenolate mofetil [CellCept] and a new drug called abatacept [Orencia, CTLA4Ig].) In addition to exploring the mechanism of action for the drug regimens in test mice, Dr. Bethunaickan aims to identify special blood and urine markers (biomarkers) that show how the kidneys in a person with lupus are faring—all key information in light of human clinical trials now underway.

"There is little question," said Dowd, "that this new round of talent will follow in the historical path of previous Foundation recipients in remaining committed to lupus and building distinguished research careers."

Other researchers currently funded through the Foundation's New Investigator Program are Philip Kahn, MD, Columbia University, Sun Jung Kim, PhD, Columbia University, Min Yang, MD, Mount Sinai School of Medicine, Zeguo Zhao, PhD, Albert Einstein College of Medicine, Giovanni Franchin, MD, PhD, Columbia University, Guillermina Girardi, PhD, Hospital for Special Surgery, Ingrid Mecklenbrauker, PhD, Rockefeller University, Meera Ramanujam, PhD, Columbia University, Ann Haberman, PhD, Yale University, Elena Peeva, MD, MSc, Albert Einstein College of Medicine.