Download Read More - Division of Rheumatology

The rheumatologists at Columbia University Medical Center/ New York-Presbyterian Hospital,
are acknowledged as leaders in the spheres of patient care, medical education, and basic and
clinical research focused on finding the causes and cures of arthritis. Given the extraordinary
medical advances that have occurred throughout the history of the Division of Rheumatology at
Columbia, our physicians are now poised to prevent many joint disorders and universally
improve the lives of patients who have arthritis.
Dr. Joan Bathon is the current director of the Division of Rheumatology at New YorkPresbyterian Hospital/Columbia University Medical Center. Prior to coming to Columbia, Dr.
Bathon served as deputy director of the Division of Rheumatology and director of the Arthritis
Center at Johns Hopkins. Dr. Bathon is the Editor-in-Chief of the American College of
Rheumatology journal, Arthritis and Rheumatism.
Dr. Bathon is a renowned clinical researcher whose research focuses on rheumatoid arthritis
and osteoarthritis; she is also a recognized authority on the arthritis-related cardiovascular risk.
Dr. Bathon is presently the principal investigator of several federal and foundation grants to
study risk factors and predictors of the enhanced risk of RA patients for accelerated
cardiovascular disease. She is the co-principal investigator of a National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS) sponsored Rheumatic Disease Research Center Core
(RDRCC), and is a co-investigator of one of the Field Centers for the “Osteoarthritis Initiative
(OAI)”, a NIAMS-sponsored large-scale longitudinal observational study of risk factors for knee
osteoarthritis.
Dr. Bathon is a former Associate Editor of Arthritis Research and Therapy and past Advisory
Editor of Arthritis and Rheumatism. She previously served as a member of the FDA Arthritis
Advisory Committee as well as a member of the Board of Directors of the American College of
Rheumatology, and of the Board of Directors of the Arthritis Foundation, Maryland Chapter. Dr.
Bathon is former Director of the Dean’s Office of Women in Science and Medicine, former CoChair of the Women’s Leadership Council, and former Chair of the Department of Medicine’s
Task Force on Academic Careers of Women in Medicine, all at Hopkins.
The Division of Rheumatology at Columbia has a long and distinguished history in the study and
treatment of rheumatic diseases and in the mentoring and training of leaders in the field of
rheumatology. For nearly a century it has been of our mission to be first and foremost in clinical
care, the training of clinician scientists, and research.
In the 1920’s, the Edward Daniels Faulkner Clinic for Arthritis was established at the ColumbiaPresbyterian Hospital. This clinic was the first clinical and research unit dedicated to rheumatic
diseases in the country. The Faulkner clinic also established the first rheumatology fellowship
program in New York.
Dr. Ralph H. Boots, a practicing rheumatologist who had done significant research on rheumatic
fever at the Rockefeller Institute for Medical Research, was the Faulkner clinic’s first director.
Together with Dr. Martin Dawson, a colleague from the Rockefeller Institute, he affected the
clinical and research arms of the clinic and ultimately brought about the rheumatology
fellowship program.
Borne from the Columbia fellowship program was the groundbreaking discovery of rheumatoid
factors and their link to rheumatoid arthritis. Dr. Charles Ragan, a rheumatology fellow, together
with Dr. Harry Rose, Chairman of the Division of Microbiology is credited with charting new
ground with this breakthrough. Dr. Ragan was an astute and gifted scientist as well as a brilliant
physician. In 1962 he was appointed the first Rheumatology Division Chief at Columbia by Dr.
Robert Loeb.
Dr. Ragan recruited and was succeeded by Dr. Charles Christian who made important
contributions to the immune complex disease in experimental rabbit models and equally
important contributions to human Systemic Lupus Erythematosus. Dr. Christian was followed by
Dr. E. Carwile LeRoy- a pioneer in scleroderma research.
In 1977 Dr. Leonard Chess was recruited to lead the Division; he served as director of the Division
of Rheumatology at Columbia for 25 years. He is presently the director of Columbia University’s
NIH designated Autoimmunity Center of Excellence (ACE). The National Institute of Health
Autoimmunity Centers of Excellence were first established in 1999; Columbia was selected as
one of four original centers. This important aspect of the Division’s lineage supports mechanistic
studies of immune therapies for rheumatic diseases and clinical trials.
An esteemed research scientist, Dr. Chess, has pioneered the identification and study of
biologically and clinically important molecules on the surface of human T lymphocytes. An
important characteristic of the Chess lab has been its ability to bring basic discoveries made at
the bench to the development of drugs employed in the treatment of human immune disease. In
this regard, Dr. Chess’ lab identified the structure and functions of key human T cell surface
molecules (including CD4, CD8, γδTCR, CD40L, α1/β1 integrin). Some of these molecules have
been employed to develop therapeutics in clinical trials of human immunologic disease:
including recombinant CD4 molecules for HIV and monoclonal anti–CD40L and anti-VLA-1 for
autoimmune disease and transplant rejection.
In the early 1980’s, in collaboration with Dr. Richard Axel, Dr. Chess defined the functions of CD4
and CD8 molecules. The work on CD4 genes enabled experiments that definitively showed that
CD4, in addition to functioning as a receptor for MHC class II, is also a HIV receptor and to clinical
trials employing recombinant soluble CD4 which blocks HIV entry into cells. In 1986 Dr. Chess
defined and isolated the first human T cells expressing the γδ T cell receptor and demonstrated
that these T cells could function to secrete lymphokines and kill tumor cells.
In the early 1990's, Dr. Chess' laboratory isolated and structurally defined a novel structure on
activated CD4 T cells termed CD40 ligand (CD40L). This molecule has been shown to mediate the
helper activity of T cells because patients with mutations in the CD40L gene have markedly
reduced and defective antibody responses and succumb to pyogenic infections. Antibodies to
CD40L were produced in Dr. Chess' lab were shown to inhibit antibody and cell mediated
immune responses and were effective in the treatment of autoimmune responses and graft
rejection in animal models and in human trials.
In more recent studies, Dr. Chess together with Dr. Hong Jiang are defining immunoregulatory
functions of MHC class I restricted CD8 T cells, which control autoimmune phenomenon in mice
and man. Moreover these regulatory cells control immune responses by perceiving the avidity of
antigen activated T cells. This has led to formulation of an avidity model of T cell regulation
which has been shown to be intimately associated with the mechanisms of self-nonself
discrimination as central function of the immune system.
In 2005 Dr. Betty Diamond was recruited to be Director of Rheumatology; after a brief tenure at
Columbia she accepted a position at the Feinstein Medical Research Facility.
Dr. Robert Winchester, a member of the Columbia University Medical Center faculty since 1991,
was appointed Director of the Division in 2007. Dr. Winchester was a pioneer in applying
immunofluorescent techniques to characterizing lymphocyte subpopulations and the reactivity
of autoantibodies with lymphocyte antigens. His introduction of (Fab’)2 fragments as
fluorescent reagents allowed exclusion of IgG as a molecule intrinsically expressed on B cells as
was the prevailing view at the time. These reagents facilitated the characterization of the
presence and complex specificity of anti-lymphocyte antibodies in lupus.
This work on fluorescent microscopy also led to his independent identification of MHC class II
molecules, with the recognition of what is now termed HLA-DR. He was the first to show HLA-DR
is expressed on B cells and monocytes and early myeloid forms, but not resting T cells. His
studies on the expression of HLA-Dr during early hematopoetic differentiation are classic
examples of the acquisition and loss of differentiation antigens with developmental stage.
Several aspects of the expression of HLA-DR were found relevant to rheumatic diseases,
including the first demonstration that fibroblastoid lineage lining cells in the rheumatoid
synovium expressed HLA-DR molecules. Activated T cells in the circulation of those with SLE, or
in the joint fluid of those with rheumatoid arthritis were shown to express HLA-DR. This was the
first demonstration that upon activation a T cell expresses novel activation molecules. This was
also one of the earliest observations that the T cells were activated in these autoimmune
diseases and pointed the way towards the importance the T cell in autoimmune disease. His use
of monoclonal antibodies led to the recognition of the monocyte antigen that is now termed
CD14, and these reagents were used to show that the synovial lining was composed of cells
derived from two distinct cell sublineages: the fibroblastoid and the myeloid.
Dr. Winchester identified various allelic forms of HLA-DR, and was the first to show that the
genetic susceptibility to systemic lupus differed from that associated with rheumatoid arthritis.
He showed susceptibility to rheumatoid arthritis was associated with HLA-DR4 and with HLADR2 and HLA-DR3 in the case of lupus. Then using early molecular biologic techniques he
contributed greatly to characterizing the structure of the MHC genes and their allelic variants.
For this work on the identification of MHC class II genes and molecules he was elected a Fellow
of the American Association for the Advancement of Science.
The genetic characterization of population differences in the association of various HLA-DR
alleles with rheumatoid arthritis resulted in the formulation of the shared epitope hypothesis.
This theory unified the seemingly capricious associations of rheumatoid arthritis susceptibility
with seemingly completely different HLA-DR alleles, by showing that they each encoded a
similar peptide binding pocket. The shared epitope has become an important tool in numerous
clinical and basic studies on rheumatoid arthritis. For this work Dr. Winchester was awarded the
Howley prize of the Arthritis Foundation.
With the appearance of the HIV epidemic Dr. Winchester described two new rheumatic diseases.
One was the syndrome of diffuse infiltrative lymphocytosis, or DILS due to exuberant CD8 T cell
response to HIV that simulated Sjogren’s syndrome. He also recognized that an inflammatory
arthritis with features of Reiter’s syndrome and psoriatic arthritis developed in those who had
the profound CD4 T cell depletion of AIDS, and used this “experiment of nature” to suggest that
the pathogenesis of these spondyloarthritis diseases did not require direct participation of CD4 T
cells and was likely mediated by CD8 T cells.
Dr. Winchester continued his focus on translational studies that seek to understand the genetic
basis of susceptibility to autoimmune disease and the mechanisms responsible for triggering and
mediating autoimmune injury. One major area of research is concerned with the genetics of
psoriatic arthritis and psoriasis that is revealing unexpected heterogeneity in the syndrome.
Other work involved studies of the T-cell repertoire and provided insight into the mechanism of
drugs used in the therapy of psoriatic arthritis, showing that methotrexate had essentially an
immunomodulatory rather than a tolerizing effect on the T cells of the joint. This also led to a
new hypothesis on the basic biology of psoriatic arthritis involved triggering by innate immune
receptors that recognized tissue injury and stress.
Dr. Winchester’s research has been performed in concert with a number of different gifted
fellows and trainees who went on to have successful independent careers in research. In
recognition of his commitment to fostering the next generation of clinical researchers, Dr.
Winchester was awarded the American College of Rheumatology Excellence in Investigative
Mentoring Award in fall 2008. Dr. Winchester currently serves as Professor of Medicine, Division
of Rheumatology at Columbia.