INNOVATION

Funding Successful Research and Driving Discovery

Findings from LRI-funded studies are among the most pivotal discoveries in lupus and autoimmunity research over the past decade – delivering results that private sector research had not previously attained. Spanning multiple organ systems and molecular aspects of the disease, scientists now look to these discoveries to inform and guide their current projects, and consistently cite LRI discoveries as a foundation for their investigations.

Immune System. In 2004, Ian Rifkin, MD, PhD (Boston University School of Medicine) demonstrated that dendritic cells are activated by DNA-autoantibody complexes through an immune receptor (TLR9) for bacterial DNA. This work, published in the Journal of Experimental Medicine, is viewed as one of the most important discoveries in lupus of the past decade and has provided novel insight into how a lupus autoantibody can activate the cells that initiate adaptive immune responses involved in lupus pathogenesis. Dr. Rifkin was awarded a $9.9 million NIH grant following this discovery to continue his research.

Kidneys. In 2002, Chaim Putterman, MD (Albert Einstein College of Medicine, New York) identified a new target of autoantibodies in the kidney. This finding, published in the Journal of Immunology, provided new insight into the mechanism of kidney damage in lupus and novel ways to monitor lupus nephritis. He was then awarded two NIH grants valued at $5.5 million to pursue his discoveries.

Central Nervous System. In 2004, Betty Diamond, MD (then at Albert Einstein College of Medicine in New York) provided the first evidence that autoantibodies are responsible for neurological complications of lupus. This finding, published in the journal Immunity, provided the first mechanistic understanding of CNS lupus, and she subsequently was awarded a $6.5 million NIH program grant to develop novel strategies for dealing with this devastating lupus-related manifestation.

Lupus Biomarkers. In 2004, Mary Crow, MD (Hospital for Special Surgery, New York) showed that genes regulated by interferon are potential biomarkers for lupus flare. This work, published in Arthritis & Rheumatism, has stimulated numerous pharmaceutical companies to test blocking interferon pathways as a possible therapeutic approach in ongoing lupus clinical trials.

Genetics. In 2006, Silvia Bolland, PhD (then at Rockefeller University, New York) showed that a strain of lupussusceptible mice carry an extra copy of the gene for an immune receptor (TLR7) for virus RNA, which helps explain why these mice develop autoantibodies to their own RNA. This work, published in Science, provided novel insights into molecular pathways of the innate immune response that can lead to lupus. It also identified new targets for lupus treatments that are being actively pursued by a number of biotech companies.

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