Professor of Medicine
Division of Pulmonary, Allergy and Critical Care MedicineDuncan Steven MD



Address: Tinsley Harrison Tower, room 422
UAB
Birmingham, AL 35294
Telephone: (205) 934-5017
Email: duncsr19@uab.edu


Publications

 

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Education


B.S. (Molecular Biology) University of Washington, Seattle, WA
M.D. University of Washington, Seattle, WA
Post-Graduate Fellowship Training:

Pulmonary Medicine (Stanford University)
Critical Care Medicine (University of Pittsburgh)
Molecular and Cellular Immunology (Scripps Research Institute)

Research Interests

Immunopathogenesis of Chronic Lung Diseases. The processes that cause several morbid lung diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), have remained enigmatic despite protracted, intense study. Probably as a result, no fundamentally new treatments, with anything more than modest effectiveness, have been implemented for these diseases in decades. My group, and others, has shown that adaptive immune responses feature prominently in both COPD and IPF. These findings include seminal demonstrations that highly activated lymphocytes, including subpopulations of end-differentiated progeny of oligoclonal expansions, with highly enhanced effector functions, are increased in the circulation and diseased lungs of these patients. Moreover, the extents of this differentiation, along with other characteristics of these lymphocytes, are highly correlated with clinical phenotypes and survival of the afflicted. Other evidences of immune involvement in these patients parallel features of conventional autoimmune disorders, including intrapulmonary over-expressions of B-cell stimulating factor (BlyS) and chemotactic mediator CXLC13. More compellingly, we have discovered direct evidence of injurious adaptive immune processes in the diseased lungs of both patient cohorts, such as immune complex and complement depositions, and infiltrations and accumulations of activated effector lymphocytes. Additional recent findings show antigen-specific cellular and humoral autoimmunity to heat shock proteins, and several other autologous peptides, is present in many of these patients. Moreover, we have also shown these autoimmune responses are singularly pathogenic and highly disease related. Studies in progress will further define and characterize these immune processes, including explorations of upstream influences (e.g., immunogenetic polymorphisms) that seem to confer predilections for the diseases. Our ultimate goal is to implement novel therapies targeted at causal pathogenic mechanisms that should have better efficacy than current, nonspecific treatments. I believe we are on the cusp of being able to do this. We have seen highly favorable initial results in a pilot study of autoantibody reduction therapies in seriously ill IPF patients, and are currently conducting a NIH-sponsored multicenter Phase II trial of rituximab in this population.