Dr. Crow is Physician-in-Chief and Chair of the Division of Rheumatology at Hospital for Special Surgery. She is also the Director of Rheumatology Research at HSS.
Dr. Crow combines basic and translational research on the mechanisms that underlie systemic autoimmune diseases with active participation in the clinical and academic programs of the hospital and Weill Cornell Medical College. Patients with systemic lupus erythematosus, rheumatoid arthritis and scleroderma have made important contributions to the understanding of those diseases through their participation in Dr. Crow’s research. Dr. Crow serves as Co-Director of the Mary Kirkland Center for Lupus Research and Director of the Autoimmunity and Inflammation Research Program at Hospital for Special Surgery.
Dr. Crow’s leadership in her field extends beyond the walls of HSS. For the past two years, she has served as President of the prestigious Henry Kunkel Society. The Kunkel Society, based at Rockefeller University, is dedicated to fostering the development of clinical investigators focused on hypothesis-driven, patient-oriented research, particularly in the field of immunology and related subjects. Dr. Crow has also continued to publish extensively in a number of highly-respected, peer-reviewed journals. This includes a recent editorial in the New England Journal of Medicine describing the significance of genetic and environmental factors in the development of lupus, as well as articles in Genes and Immunity and Arthritis and Rheumatism on interferon-alpha as a heritable risk factor for lupus.
Physician-in-Chief, Hospital for Special Surgery
Chair, Division of Rheumatology, Hospital for Special Surgery
Senior Research Scientist, Hospital for Special Surgery
Professor of Medicine, Weill Cornell Medical College
Attending Physician, New York Presbyterian Hospital
Systemic lupus erythematosus
Arthritis Hero, Arthritis Foundation, 2001
Joseph P. Routh chair, 2010
American College of Rheumatology, President-Elect
Member, Medical Advisory Committee, The S.L.E. Foundation, Inc.
MD, Weill Cornell Medical College, New York, 1978
New York Hospital, Internal Medicine, New York, 1978-1979
New York Hospital, Internal Medicine, New York, 1979-1981
Rockefeller University, Immunology Research, New York, 1981-1984
Hospital for Special Surgery, Rheumatology, New York, 1981-1984
Chernysheva AD, Kirou KA, Crow MK. T cell proliferation induced by autologous non-T cells is a response to apoptotic cells processed by dendritic cells. J Immunol 169:1241-1250, 2002.
Roman MJ, Shanker B-A, Davis A, Lockshin MD, Sammaritano L, Simantov R, Crow MK, Schwartz JE, Paget SA, Devereux RB, Salmon JE. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 349:2399-406, 2003.
Crow MK, Kirou KA, Wohlgemuth J. Microarray analysis of interferon-regulated genes in SLE. Autoimmunity 36:481-490, 2003.
Crow MK. Type I interferon and autoimmune disease. Autoimmunity 36:445-446, 2003.
Crow MK: Costimulatory molecules and T cell-B cell interactions. Rheum Dis Clin N Amer, 30:175-191, 2003.
Crow MK, Kirou KA. Interferon-alpha in systemic lupus erythematosus. Curr Opin Rheum, 16:541-547, 2004.
Liu S, Cerutti A, Casali P, Crow MK. Ongoing immunoglobulin class switch DNA recombination in lupus B cells: analysis of switch regulatory sequences. Autoimmunity, 37:431-443, 2004.
Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MGE, Ly N, Woodward RN, Fry KE, Lau A Y-H, Prentice JG, Wohlgemuth JG, Crow MK. Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum, 50:3958-67, 2004.
Kirou KA, Lee C, George S, Louca K, Peterson MGE, Crow MK. Interferon-alpha pathway activation identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum, 52:1491-503, 2005.
Roman MJ, Devereux RB, Schwartz JE, Lockshin MD, Paget SA, Davis A, Crow MK, Sammaritano L, Levine DM, Shankar B-A, Moeller E, Salmon JE. Arterial Stiffness in Chronic Inflammatory Diseases. Hypertension, 46:194-9, 2005.For more publications, please see the PubMed listing.
Dr. Crow’s investigations focus on the genetic contributors, mechanisms of induction and clinical implications of the increased presence of Type I interferon (IFN) in systemic autoimmune diseases, particularly lupus. Her work has shown that a specific molecule known as interferon-alpha is evident in large quantities in patients with lupus. Interferon-alpha primes the body’s immune system to turn on and, in some cases, initiate an autoimmune attack on itself. Statistical tests have linked genetic variants with high levels of IFN, which may in turn predispose a person to lupus. However, the disease generally appears only when something else, perhaps an environmental factor, pushes the immune system to the breaking point and causes the production of the damaging autoantibodies.
The team in Dr. Crow’s laboratory has also observed that lupus patients with IFN pathway activation are more likely to have severe disease, including renal involvement, than those who do not have IFN pathway activation. In order to understand the mechanisms and features of disease in these patients, they are now studying the capacity of immune complexes to activate either the IFN pathway or alternative molecular pathways and are determining the distinct clinical features associated with each of these mechanisms.
In keeping with the Hospital’s efforts to link basic science and clinical research, Dr. Crow and her team have been collecting clinical information on lupus patients at least every three months and quantifying expression of candidate biomarkers, including components of the IFN pathway, in order to relate changes in biology to fluctuations in disease. The information generated in this study is helping to highlight the underlying mechanisms responsible for lupus and may lead to practical application in the setting of clinical practice. For example, data gathered from the Hospital’s pool of patients suggests that an increase in IFN in a patient’s blood could actually serve as a biomarker that predicts a future flare in disease, even in the absence of symptoms. Dr. Crow’s work has formed the basis of current drug development programs at numerous pharmaceutical and biotechnology companies, and early results from those trials support the efficacy of inhibiting the IFN pathway therapeutically. The basic science work conducted in Dr. Crow’s laboratory carries the potential for a major breakthrough in the treatment of lupus – the first in more than three decades. These new therapies hold the promise of dramatically improving the lives of those with lupus and may potentially be used in the treatment of scleroderma and rheumatoid arthritis as well.
The immune system has evolved to maintain the integrity of the organism in an environment rich in infectious microbes. When the immune system becomes misdirected toward components of one’s own tissue, autoimmune disease and chronic inflammation can result. In systemic lupus erythematosus (SLE), the prototype systemic autoimmune disease, proteins present in intracellular particles, along with the DNA or RNA bound by those proteins, are targeted by lymphocytes and antibodies of the immune system, resulting in inflammation and widespread tissue damage. This autoreactive immune response is mediated by CD4+ helper T lymphocytes that orchestrate a coordinated program of immune and inflammatory functions through interactions with B lymphocytes, macrophages, dendritic cells, as well as cells outside the immune system, such as the endothelial cells that line blood vessels. The goals of the laboratory are to define the triggers of immune activation in autoimmune disease and to characterize the mechanisms used by the immune system to regulate the effector cells that contribute to inflammation and tissue damage.
A current paradigm proposes that apoptotic cells may serve as a source of the self-antigens that initiate autoimmunity. However, all individuals are exposed to apoptotic cells. Our challenge is to understand why some individuals develop autoimmune disease and others do not. We propose that while apoptotic cells may serve as one source of self-antigen, adjuvant-like factors in the immune microenvironment of some individuals promote the effective presentation of available antigens to CD4+ T cells, resulting in T cell activation and generation of effector mechanisms targeted at self-antigens. Active projects include identification of the stimuli and molecular pathways involved in induction of type I interferon in SLE, with genome-derived immunostimulatory DNA and double stranded or single stranded RNA potential mediators of this effect; characterization of proinflammatory gene products produced in SLE and associated with active disease; and investigation of the relationship between interferon pathway activation and production of specific autoantibodies, particularly those targeting RNA-binding proteins.
As clinical investigators, we search for applications of our laboratory studies that may have impact on patients with disease. Efforts underway are aimed at identifying novel approaches to inhibition of the type I interferon pathway that may inform development of new therapeutic interventions in SLE. We are identifying the gene products that are differentially expressed between SLE patients with and without accelerated atherosclerosis, with the aim of characterizing novel targets that could modulate development of this clinically important outcome. Finally, we are studying the contribution of immune system activation and inflammation to disease in patients with osteoarthritis.
Mechanisms of autoimmune disease
Genomic triggers of autoimmunity
Systemic lupus erythematosus