Duane R Wesemann, M.D., Ph.D.
|Title||Assistant Professor of Medicine|
|Institution||Brigham and Women's Hospital|
|Address||Brigham and Women's Hospital|
Smith Bldg, 638 A
1 Jimmy Fund Way
Boston MA 02115
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2008||Outstanding Fellow Award for excellence in teaching|
2010||AAAAI-GSK Career Development Award|
2011||AAAAI-Baxter Career Development Award|
2013||Young Investigator Award in Primary Immune Deficiency|
2016||Burroughs Wellcome Career Award for Medical Scientists|
2015||Young Investigator Award in Mucosal Immunity|
A diverse repertoire of immunoglobulins (antibodies) is required to build effective immunity against a vast array of infectious threats. However, expanded immunoglobulin diversity raises the risk of generating antibodies directed against self or otherwise innocuous environmental components, which can lead to autoimmune and allergic disorders, respectively. Our lab studies the process of primary immunoglobulin repertoire diversification and how environmental factors, such as commensal microbes and diet, may influence the structure and depth of this diversity. We are particularly interested in how exposures early in life may shape this process. As we work to identify principles regulating the host:environment interactions that modulate the immune system, we seek to deepen our understanding of how this may impact the development of immunity to infection and efficacy of vaccination. In addition, we are undertaking innovative approaches to uncover therapeutic targets for the treatment of allergic disorders such as food allergies and asthma. Please visit the wesemann lab website
Available: 06/02/14, Expires: 09/30/15
Allergic diseases such as asthma, allergic rhinitis, food allergy, and eczema are associated with alterations in human microflora, yet the causal role of microbial communities in these disease processes and their effects on host immune function is poorly understood. Recent work in mouse models has shown that gut microbes play key roles in regulating host immune system development and the host immune system in turn regulates gut microbe composition. Intestinal colonization with microflora occurs shortly after birth with increasing microbial diversity in the first months of life but the factors influencing the establishment and composition of microbial communities are incompletely defined. As a part of the adaptive immune system, which works together with innate immune components to regulate microbial communities, mucosal B lineage cells develop a diverse repertoire of antibodies able to bind a wide array of microbes. This antibody repertoire is the substrate for selection and expansion of clones that work to clear infections and contain commensals. Our preliminary studies in mice suggest that colonization with microbes during weaning age provides signals to developing B lineage cells within the intestine to modify the antibody repertoire very early in life. These findings suggest a developmental window where microbe:host immune system interactions both affect the development of the humoral immune response and the potential establishment of niches for commensal and mutualistic communities. Most allergic disease begins in early childhood, and given the associations of allergy and microflora, we believe that early microbe-host interactions are highly relevant for understanding the development of immune responses and disease.
Our lab has been collecting human samples for the evaluation of the microbiome and immunoglobulin repertoire from newborns and mothers. Samples are currently being prepared for next generation sequencing technologies to identify correlations between microbial membership and immunoglobulin diversity. The summer student project would entail sequencing data handling and analysis. In this regard, prior experience in computer programming, statistics, and handling of large data sets would be helpful.
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