Richard Bucala, MD, PhD
Waldemar Von Zedtwitz Professor of Medicine (Rheumatology) and Professor of Pathology and of Epidemiology (Microbial Diseases)Cards
About
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)
Academic Achievements & Community Involvement
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
Fact Sheets
Interstitial Lung Disease (ILD)
Learn More on Yale Medicine
Board Certifications
Rheumatology
- Certification Organization
- AB of Internal Medicine
- Latest Certification Date
- 2018
- Original Certification Date
- 2004
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