Mary K. Crow, MD

Hospital for Special Surgery, New York, NY
2004 Biomarkers

2001 General Immune System Function
2001 Biomarkers

With her first LRI grant, in 2001, Dr. Crow investigated the novel hypothesis that the products of viral-like “junk” DNA found between genes, called transposons, might stimulate the production of interferon-alpha—and in this way contribute to autoimmunity.

Dr. Crow’s findings, including increased expression of transcripts encoded by long interspersed nuclear elements (LINE-1) in peripheral blood of some people with lupus, led to funding of an NIH R21 grant and further development of this provocative research direction. Recent data are linking LINE-1 transcripts to production of interferon-alpha.

With her second LRI grant, in 2004, Dr. Crow set out to identify and validate patterns of gene activity that could be used as actual biomarkers of lupus flare.

Her lab initiated a longitudinal study to examine three patterns of gene activity—interferon signature, inflammatory signature, and TLR/VEGF signature—to see if these might serve as effective biomarkers.

“By identifying good markers that measure the early phase of disease activity and, in particular, flares, we can one day intervene earlier with new or existing drugs and treat a patient before disease becomes clinically active,” Dr. Crow explained. “To know if a drug works, we have to assess how active the disease is and how that activity changes in response to the drug.”

Among other discoveries generated by LRI funding, Dr. Crow developed an informative assay of serum interferon activity that has been essential in defining genetic contributions to interferon pathway activation and autoimmunity.

Thanks to a large lupus patient and family registry developed with the assistance of organizations such as the S.L.E. Lupus Foundation, her laboratory demonstrated that production of interferon is a heritable trait that might be used to predict those at risk of developing the disease in the first place.

With her colleague Kyriakos Kirou and collaborator Tim Niewold, Dr. Crow is continuing the longitudinal study of lupus patients to unravel the molecular pathways involved in innate immune system activation in lupus and the determinants of increased disease activity.

A goal of this work is to gain new understanding of pathogenic mechanisms and markers of disease activity that will guide patient management as innovative new therapies are developed.

Select publications:

Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MG, Ly N, Woodward RN, Fry KE, Lau AY, Prentice JG, Wohlgemuth JG, Crow MK. Arthritis Rheum. 2004 50(12):3958-67.

Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. Arthritis Rheum. 2005 52(5):1491-503.

Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies. Hua J, Kirou K, Lee C, Crow MK. Arthritis Rheum. 2006 54(6):1906-1916.

High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK. Genes Immun, 2007 Sep;8(6):492-502. Epub 2007 Jun 21.

Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Niewold TB, Kelley JA, Flesch MH, Espinoza LR, Harley JB, Crow MK. Arthritis Rheum 2008; 58:2481-7.

Ongoing funding:

Dr. Crow won a $1.820 million NIH R01 grant to continue her work on activation of the interferon pathway in lupus, as well as a $50,000 grant from the Mary Kirkland Center for Lupus Research grant (at the Hospital for Special Surgery). She also received a total of $275,000 from the Alliance for Lupus Research (ALR) to expand on her LRI findings.

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