Richard Bucala, M.D., Ph.D.Professor of Medicine, Pathology, and Epidemiology at Yale University School of Medicine
Richard Bucala was born in 1957, grew up in greater Hartford Connecticut and matriculated at Yale College, where he received a combined BS/MS degree summa cum laude. He entered the Cornell/Rockefeller MD/PhD program in 1979 and performed dissertation work under Anthony Cerami. After a visiting fellowship in genetics at the Institut Pasteur in Paris, he completed internship and residency training in Internal Medicine at the Brigham & Women’s Hospital. In 1988, he was awarded a Brookdale National Fellowship and returned to Rockefeller for a research fellowship and clinical training in Rheumatology under Dr. Charles Christian at the Hospital for Special Surgery. In his post-doctoral research, he observed that vascular glycation products quenched the vasodilator nitric oxide (15), and he developed the first immunoassay for glycation damage (19). He was appointed Assistant Professor at Rockefeller in 1990 and was subsequently recruited to the newly-established Picower Institute, where he became Scientific Director in 1999. His investigations there included the cloning of the cytokine macrophage migration inhibitory factor (MIF) (26), the discovery of the circulating fibrocyte (36), and the description of a novel phosphofructokinase gene regulating the Warburg effect (aerobic glycolysis) (106). Dr. Bucala was recruited to Yale as Professor of Medicine in 2002 and appointed to its School of Public Health in 2006.
Dr. Bucala studies the regulation of the immune system with a focus on how protective responses can lead to immunopathology and disease. His research has led to novel therapies in advanced clinical testing to correct imbalances in immunologic, metabolic, and repair responses. His laboratory’s main emphasis is in the area of MIF-family cytokines, their role in genetic susceptibility to disease, and their therapeutic targeting (592). The Bucala group discovered MIF’s regulation of glucocorticoid immunosuppression (45), which opened novel approaches to therapy (70,121), identified the two-component MIF receptor (162,201), and discovered commonly occurring functional polymorphisms in the MIF gene, which show global population stratification (196). Depending on the nature of the immune or invasive provocation, variant MIF alleles may protect from disease or contribute to pathology in autoimmunity (145,203,291,395,405) and in different acute or chronic infections (240,333). The laboratory developed biochips to determine MIF polymorphisms in resource-limited settings (184), with applications to malaria and tuberculosis (246,314), and it enjoys long-standing collaborations with the Macha Malaria Research Institute and the University of Zambia for research and for clinical training.
Translational medicine is a major thematic focus, and the laboratory is leading efforts to develop MIF-based therapies that may be tailored to an individual’s genetic makeup (370,385). A licensed anti-MIF antibody (Imalumab) has completed phase II clinical testing and an anti-MIF receptor (Milatuzumab) was recently approved for oncology and is undergoing phase II clinical trials in SLE (277). Close research partnerships in structure-based drug design have led to novel and orally active small molecule MIF antagonists (233). First-in-class molecules developed in 2012 provided Yale with its most lucrative licensing agreement up until that time. Small molecule MIF agonists also have been developed for application as adjuvants and in ischemic tissue protection (222,329). The function of the MIF-like genes expressed by the parasites responsible for malaria, leishmaniasis, and hookworm infection are under active investigation (227,298), and have been found to suppress T cell memory and patented as novel vaccine targets (407).
Dr. Bucala also is credited with the discovery of the fibrocyte, a circulating connective tissue cell that contributes to the pathogenesis of different systemic and organ-specific fibrosing disorders (75). Fibrocytes in circulation have prognostic utility and a fibrocyte-directed biologic agent (PRM-151) has recently entered phase III clinical testing in myelofibrosis and in interstitial lung disease (564).
Dr. Bucala is an inventor on over 30 issued patents, with licensed technologies that include a diagnostic ELISA for protein glycation, anti-MIF and anti-MIF receptor antibodies, genetic tests for MIF, and small molecule cytokine modulators. His discoveries led to the founding of the biotechnology companies Cytokine Networks and MIFCOR; the latter in 2015 with three students at Harvard Business School.
Dr. Bucala has trained more than 60 scientists during his career and several have achieved positions of medical and scientific leadership, including one Chair of Medicine, two Division Chiefs in Medicine, a Department Chair in Biochemistry, a cancer center clinical trials director, and two heads of drug and vaccine development in the pharmaceutical industry. Over the last ten years, Dr. Bucala has mentored five recipients of career development awards. Each advanced to an independent faculty position, including one at Johns Hopkins (Hematology), two at the University of Pennsylvania (Rheumatology, Infectious Diseases), and two at Yale (Digestive Diseases, Pulmonary and Critical Care Medicine). Dr. Bucala attends at Yale-New Haven Hospital on the Rheumatology consult service and formerly in the Department’s physician-scientist in-patient service. He teaches in the Schools of Medicine and Public Health, and in Yale College on the topics of inflammation, autoimmunity, immunotherapy, and malaria. His sabbaticals have included public health and human genetic projects in Africa. Under the auspices of the International League against Rheumatism, he led the development of the first Rheumatology training program in Zambia and the founding of the Rheumatologic Association of Zambia, and he serves as a medical advisor to the University Teaching Hospital in Lusaka (331,575).
Dr. Bucala was elected to the American Society for Clinical Investigation and the Association of American Physicians. He has been a permanent member of two NIH Study Sections and has served on several Editorial Boards. He is the outgoing Editor-in-Chief of the American College of Rheumatology’s primary publication Arthritis & Rheumatology (term: 2015-2020). He led efforts to enhance the journal’s utility to the college, which included improving its citation impact factor (by 60%), increasing the publication of clinical trials, introducing a program for CME credit, modernizing its print and online format, and launching a new open-access companion journal.