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Prof. Richard Bucala, MD, PhD
Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Professor of Medicine (Rheumatology), of Epidemiology (Microbial Diseases) and of Pathology.
Education & Training:
|MD||Cornell College (1986)|
|PhD||Rockefeller University (1985)|
|BS||Yale University (1979)|
|MS||Yale University (1979)|
|Fellow||Hospital for Special Surgery|
|Resident||Brigham & Women’s Hospital/Harvard Medical School|
|Visiting Fellow||Institut Pasteur, Paris|
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, a clinical problem that restricts the effective treatment of autoimmune diseases such as rheumatoid arthritis.
Our laboratory investigations encompass the biochemical, biological, and genetic 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 MIF that 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 studies are 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.