The S.L.E. Lupus Foundation, the nation’s leading organization providing patient services, education and funding for lupus research, has named Mark J. Shlomchik, M.D., Ph.D., professor of laboratory medicine and immunobiology, its scientific honoree for the year 2006.
Shlomchik studies the role of B cells, immune system cells produced in bone marrow, in systemic lupus erythematosus (SLE) and other autoimmune diseases.
Normally B cells help to protect the body from infectious agents, but in SLE unknown environmental or genetic factors cause these cells to go awry and to produce antibodies to DNA, RNA and other proteins found in every cell in the body. For this reason lupus affects many of the body’s own organs, especially the heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system. These “autoreactive” B cells also cause the immune system’s T cells to target these organs, leading to further damage.
SLE is a chronic condition with a vicious cycle: as the body’s damaged tissue becomes inflamed, more auto-reactive B cells are produced. For reasons that are not fully understood, the symptoms of lupus—joint pain, fever, skin disorders and fatigue, among others—wax and wane, occurring in intermittent bursts known as “flares.” The most common treatments used during flares are corticosteroids or other drugs that suppress the immune system. But these drugs have serious side effects, including increased susceptibility to infection, obesity, diabetes, osteoporosis, hypertension and cataracts, so there is an urgent need to understand the cellular and molecular mechanisms that cause flares and to develop new drugs to prevent them.
As part of this effort, Shlomchik, professor of laboratory medicine and immunobiology, has focused his recent research on the so-called toll-like receptors (TLRs) of the innate immune system (see related story, “Immunology Comes of Age”). It had long been suggested that B cells might become autoreactive by somehow recognizing DNA or RNA in the cells that form the body’s organs. During the past five years, it was shown that TLR9 and TLR7, both of which are expressed on B cells, are specific, respectively, for DNA and RNA.
Following up on this work, Shlomchik and his colleagues reported in 2006 in the journal Immunity that lupus-prone mice lacking TLR9 and TLR7 did not generate antibodies against DNA and RNA, and that lupus-like symptoms in mice lacking TLR7 were far less severe. These findings suggest that developing drugs that target TLRs could be valuable new treatments for lupus and other autoimmune diseases.
After receiving his M.D. and Ph.D. degrees from the University of Pennsylvania, Shlomchik joined the Yale faculty as an assistant professor in 1993 and rose through the ranks to become professor in 2004.
He serves on the scientific advisory board of the S.L.E. Lupus Foundation’s Lupus Research Institute and is co-chair of its Novel Research and Peer Review task forces. He is also Associate Director of the Yale-New Haven Hospital Blood Bank.
The foundation paid tribute to Shlomchik at its annual gala, held last December at the Marriott Marquis hotel in New York City, saying that he had brought “invaluable insight, encouragement, and direction to the Lupus Research Institute, helping to take it to new levels of scientific excellence.”
The event’s master of ceremonies was NBC Sports and HBO sportscaster Bob Costas, and entertainment was provided by soprano Barbara Cook, a star of the musical theatre for over 50 years.
The foundation also honored James D. Robinson III, M.B.A., chairman of the board of Bristol-Myers Squibb, for his company’s development of abatacept (Orencia), a non-steroidal anti-inflammatory agent. Abatacept has won Food and Drug Administration approval for the treatment of rheumatoid arthritis and is now in being tested in a multicenter Phase II trial for treating and preventing lupus flares.