My career as a physician-scientist has provided me with both the scientific and medical expertise and the mentoring skills necessary to contribute meaningfully to this training program. Since my first faculty appointment in 1991, I have trained nearly 50 scientists in my laboratory. Several of these individuals have advanced to prominent positions of medical and scientific leadership, and they include two chairs of medicine, two division chiefs in departments of medicine, a department chair in biochemistry, a clinical trials director, and two division chiefs for drug and vaccine development in the pharmaceutical industry. Over the prior ten years, I have mentored five recipients of career development awards; four of these individuals advanced to junior faculty positions at Johns Hopkins (Hematology), the University of Pennsylvania (Rheumatology, Infectious Diseases), and Yale (Digestive Diseases), and one is a senior fellow in Yale’s Section of Pulmonary and Critical Care Medicine.
My laboratory investigates the mechanisms by which host immunity converts from a protective response to one producing disease and our current focus is on the role of the MIF cytokine family and functional MIF polymorphisms in autoimmunity. These investigations have encompassed structure-function, signal transduction, and genetic studies. We are credited with cloning MIF and its receptor, the discovery of MIF polymorphisms and their association with disease, and the development of biologic and small molecule MIF antagonists for clinical use. We also discovered the circulating fibrocyte and defined its role contribution to different fibrosing disorders. Our research has led directly to clinical trials for humanized anti-MIF in lupus nephritis and lymphoma (ClinicalTrials.gov: NCT01541670, NCT01765790), and to an anti-fibrocyte therapy for idiopathic pulmonary fibrosis and myelofibrosis (ClinicalTrials.gov: NCT01254409, NCT01981850). Our discovery of functional polymorphisms in human MIF have underscored MIF’s pathogenic role and we have participated in several genetic epidemiology studies (GenIMS, VCRC, WIGGR, SLEGEN) to define the influence of MIF alleles in different autoimmune and infectious diseases. We also investigate the relationship between autoimmunity and malaria. This work led to field studies in immunogenetics and prompted our development of a robust biochip for DNA genotyping suitable for resource-limited settings that required no detector instrumentation. We trained Zambian scientists in its use and we have supported several US Down’s and Fogarty Fellows in genetics work in Zambia, Kenya, and Uganda. These research studies ultimately led to our current ACR-International League against Rheumatism clinical program to enhance rheumatology education and training in Zambia.