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Richard Bucala, MD, PhD

Waldemar Von Zedtwitz Professor of Medicine (Rheumatology) and Professor of Pathology and of Epidemiology (Microbial Diseases)
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Additional Titles

Chief, Rheumatology, Allergy, & Immunology

Affiliated Faculty, Yale Institute for Global Health

Rheumatologist in Chief, Rheumatology, YNHH

About

Titles

Waldemar Von Zedtwitz Professor of Medicine (Rheumatology) and Professor of Pathology and of Epidemiology (Microbial Diseases)

Chief, Rheumatology, Allergy, & Immunology; Affiliated Faculty, Yale Institute for Global Health

Positions outside Yale

Rheumatologist in Chief, Rheumatology, YNHH

Biography

Richard Bucala, MD, PhD, is Chief, Section of Rheumatology, Allergy & Immunology and the Waldemar Von Zedtwitz Endowed Professor of Medicine, Pathology, and Epidemiology & Public Health. He studies the regulation of the immune system with a focus on how protective responses can lead to immunopathology and disease. His laboratory’s main emphasis is MIF-family cytokines, their role in genetic susceptibility to disease, and their therapeutic targeting for different clinical conditions. The Bucala group is credited with the molecular cloning of MIF and discovery of its critical role in regulating glucocorticoid immunosuppression, which opened novel approaches to therapy in autoimmune inflammatory conditions. His lab also identified the MIF receptor and discovered common polymorphisms in the MIF gene, which show global population stratification. Depending on the nature of the immune or invasive provocation, variant MIF alleles protect from disease or contribute to immunopathology in autoimmunity and in different infections and chronic conditions. His laboratory developed biochips for genetic epidemiology studies of malaria and tuberculosis in resource-limited settings, and his research is leading efforts to develop MIF-based therapies tailored to an individual’s genetic makeup. Dr. Bucala licensed anti-MIF toward the development of Imalumab and his work contributed to the FDA-approved anti-MIF receptor antibody (Milatuzumab). Research partnerships in structure-based drug design have led to novel small molecule MIF modulators for use in autoimmune, oncologic, and infectious diseases. The function of the MIF-like genes expressed by the parasites responsible for malaria, leishmaniasis, and helminthic infection also are under investigation. As these proteins were discovered to uniquely suppress immunologic memory, they offer new targets for vaccination against these infections. Dr. Bucala further is credited with the discovery of the circulating fibrocyte, which is being targeted therapeutically in different fibrosing disorders. He co-founded two biotechnology companies, including the startup MIFCOR begun as a student-advised project. He attends in the Yale New Haven Health System in-patient service and is the past Editor-in-Chief of Arthritis & Rheumatology. Dr. Bucala was elected to the American Society for Clinical Investigation and the Association of American Physicians and has served on advisory boards for the UN, the federal government, the pharmaceutical industry, academia, and private foundations.

Appointments

Education & Training

Fellow
Hospital for Special Surgery (1991)
Resident
Brigham & Women's Hospital/Harvard Medical School (1988)
MD
Cornell College (1986)
PhD
Rockefeller University (1985)
Visiting Fellow
Institut Pasteur, Paris (1985)
BS
Yale University (1979)
MS
Yale University (1979)

Research

Overview

We seek to understand the mechanisms by which host immunity converts from a protective response to one producing disease and tissue pathology. A main focus of our efforts is on the cytokine, MIF, which we cloned from the pituitary gland and discovered to counter-regulate the immunosuppressive actions of glucocorticoids. MIF production is tightly linked to the expression of many autoimmune and inflammatory diseases, and anti-MIF strategies are effective in reducing immunopathology in many experimental models of disease.An important goal for us is to elucidate the emergence of steroid resistance, aclinical problem that restricts the effective treatment of autoimmune diseases such as rheumatoid arthritis.

Our laboratory investigations encompass the biochemical, biological, andgenetic characterization of MIF, and we remain focused on understanding MIF's role in physiology and pathology. We have uncovered a unique action for MIF in sustaining inflammatory signal transduction, a pathway that impacts on the proliferation and long-term activation of many cell types. Our studies support an important role for MIF in inhibiting p53-dependent growth arrest, which isan action that sustains the pro-inflammatory phenotype of monocytes/macrophages. We have discovered functionally important polymorphisms in the promoter for human MIFthat are associated with the severity immunologic diseases such as rheumatoid arthritis, asthma, and SLE.Additionally, they play a role in the inflammatory pathogenesis of malignancies such as prostate cancer and in the neurodevelopmental disorder, autism.

We initiated studies of MIF's role in the development of severe malarial anemia, which is the proximate cause of death in the nearly 1.5 million deaths that occur annually from malaria. We conduct clinical studies in Zambia to examine the clinical frequency of different MIF genetic polymorphisms in an effort to understand why severe malaria develops in certain children. Additional studiesare underway in to examine the role of MIF in Leishmaniasis and in tuberculosis. Population stratification of high and low expression forms of the MIF gene appear to account for differential susceptibility to malaria or autoimmunity.

In a separate line of investigation, we study the biology of fibrocytes,a blood-borne cell with inflammatory and fibrogenic properties. We first characterized these cells in studies of wound repair and granuloma formation, and we are exploring their role in different systemic fibroses.

Medical Subject Headings (MeSH)

Africa; Communicable Diseases, Emerging; Epidemiology; Global Health; Infectious Disease Medicine; Macrophage Migration-Inhibitory Factors; Malaria; Pathology; Public Health; Rheumatology; Stem Cells

Research at a Glance

Yale Co-Authors

Frequent collaborators of Richard Bucala's published research.

Publications

Featured Publications

2024

Academic Achievements & Community Involvement

  • activity

    Arthritis & Rheumatology

  • activity

    Journal of Immunology

  • activity

    Alumni Schools Committee

  • activity

    NIH

  • honor

    American Association of Physicians

Clinical Care

Overview

Richard Bucala, MD, PhD, is a rheumatologist, pathologist, and epidemiologist, and serves as chief of Rheumatology, Allergy & Immunology.

Rheumatic disease is an umbrella term for conditions that affect the joints, tendons, muscles, and ligaments. Thirty percent of patients over the age of 65 suffer from a rheumatologic disorder, mostly from degenerative arthritis, Dr. Bucala notes.

“It’s a major reason for why older patients are not able to do all the things that they would like to do. At Yale, we offer multidisciplinary specialty care. A rheumatic disease can affect several organ systems. So, we aspire to have patients come in and see rheumatology but also any associated specialists, from cardiology to dermatology to pulmonology to gastroenterology, in one day” Dr. Bucala says. “This way, all the information and knowledge is put together in one place at one point in time. This allows the physician team to provide the best assessment and information and ultimately therapy for the patient.”

Gathering this information comprehensively allows the medical providers to provide the most accurate and fastest diagnosis and to offer the most advanced treatments, he adds.

“Because most of the diseases we take care of are chronic, there are no easy or ready cures. We aim to prevent the progression of disease so that patients can maintain their function and their lifestyles to the extent that they can,” he says.

Personalized, precision medicine is key to the rheumatology specialty, he adds. “We understand that in rheumatology, there is a particular expression of disease which often is unique to patients. So, we need to know our patients well and to understand their symptoms in the best possible way so we can apply the most specific therapies, which will be effective and with the least toxicity,” Dr. Bucala says.

Dr. Bucala’s research focuses on developing immunotherapies that are tailored to a patient’s genetic makeup. “We study why certain genetic attributes allow people to, for instance, have a mild infection or combat influenza or another type of infection,” he says. “Our work has allowed us to identify patients who are at high risk for having more severe joint destruction in arthritis or more severe renal and central nervous disease in lupus, for instance. We've also developed particular therapies, so-called ‘biologic therapies,’ that target particular pathways, which are the same pathways that are expressed by a person's genetic susceptibility.”

Clinical Specialties

Rheumatology; Pathology

Fact Sheets

Board Certifications

  • Rheumatology

    Certification Organization
    AB of Internal Medicine
    Latest Certification Date
    2018
    Original Certification Date
    2004

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Locations

  • The Anlyan Center

    Academic Office

    300 Cedar Street, Ste S541D

    New Haven, CT 06519

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