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Duane R Wesemann, M.D., Ph.D.

TitleAssistant Professor of Medicine
InstitutionBrigham and Women's Hospital
DepartmentMedicine
AddressBrigham and Women's Hospital
Smith Bldg, 638 A
1 Jimmy Fund Way
Boston MA 02115
Fax617/264-6346
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 Biography 
 awards and honors
2008 - 2008Outstanding Fellow Award for excellence in teaching
2009 - 2010AAAAI-GSK Career Development Award
2010 - 2011AAAAI-Baxter Career Development Award
2011 - 2013Young Investigator Award in Primary Immune Deficiency
2011 - 2016Burroughs Wellcome Career Award for Medical Scientists
2013 - 2015Young Investigator Award in Mucosal Immunity

 Overview 
 overview
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.


 Mentoring 
 current student opportunities
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.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Tong P, Wesemann DR. Molecular Mechanisms of IgE Class Switch Recombination. Curr Top Microbiol Immunol. 2015; 388:21-37.
    View in: PubMed
  2. Gallagher MP, Shrestha A, Magee JM, Wesemann DR. Detection of True IgE-expressing Mouse B Lineage Cells. J Vis Exp. 2014; (94).
    View in: PubMed
  3. Wesemann DR, Portuguese AJ, Meyers RM, Gallagher MP, Cluff-Jones K, Magee JM, Panchakshari RA, Rodig SJ, Kepler TB, Alt FW. Microbial colonization influences early B-lineage development in the gut lamina propria. Nature. 2013 Sep 5; 501(7465):112-5.
    View in: PubMed
  4. Callen E, Di Virgilio M, Kruhlak MJ, Nieto-Soler M, Wong N, Chen HT, Faryabi RB, Polato F, Santos M, Starnes LM, Wesemann DR, Lee JE, Tubbs A, Sleckman BP, Daniel JA, Ge K, Alt FW, Fernandez-Capetillo O, Nussenzweig MC, Nussenzweig A. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell. 2013 Jun 6; 153(6):1266-80.
    View in: PubMed
  5. Wesemann DR, Portuguese AJ, Magee JM, Gallagher MP, Zhou X, Panchakshari RA, Alt FW. Reprogramming IgH isotype-switched B cells to functional-grade induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2012 Aug 21; 109(34):13745-50.
    View in: PubMed
  6. Oksenych V, Alt FW, Kumar V, Schwer B, Wesemann DR, Hansen E, Patel H, Su A, Guo C. Functional redundancy between repair factor XLF and damage response mediator 53BP1 in V(D)J recombination and DNA repair. Proc Natl Acad Sci U S A. 2012 Feb 14; 109(7):2455-60.
    View in: PubMed
  7. Wesemann DR, Magee JM, Boboila C, Calado DP, Gallagher MP, Portuguese AJ, Manis JP, Zhou X, Recher M, Rajewsky K, Notarangelo LD, Alt FW. Immature B cells preferentially switch to IgE with increased direct Sµ to Se recombination. J Exp Med. 2011 Dec 19; 208(13):2733-46.
    View in: PubMed
  8. Basu U, Meng FL, Keim C, Grinstein V, Pefanis E, Eccleston J, Zhang T, Myers D, Wasserman CR, Wesemann DR, Januszyk K, Gregory RI, Deng H, Lima CD, Alt FW. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell. 2011 Feb 4; 144(3):353-63.
    View in: PubMed
  9. Zha S, Guo C, Boboila C, Oksenych V, Cheng HL, Zhang Y, Wesemann DR, Yuen G, Patel H, Goff PH, Dubois RL, Alt FW. ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks. Nature. 2011 Jan 13; 469(7329):250-4.
    View in: PubMed
  10. Boboila C, Yan C, Wesemann DR, Jankovic M, Wang JH, Manis J, Nussenzweig A, Nussenzweig M, Alt FW. Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4. J Exp Med. 2010 Feb 15; 207(2):417-27.
    View in: PubMed
  11. Boboila C, Jankovic M, Yan CT, Wang JH, Wesemann DR, Zhang T, Fazeli A, Feldman L, Nussenzweig A, Nussenzweig M, Alt FW. Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70. Proc Natl Acad Sci U S A. 2010 Feb 16; 107(7):3034-9.
    View in: PubMed
  12. Wang JH, Gostissa M, Yan CT, Goff P, Hickernell T, Hansen E, Difilippantonio S, Wesemann DR, Zarrin AA, Rajewsky K, Nussenzweig A, Alt FW. Mechanisms promoting translocations in editing and switching peripheral B cells. Nature. 2009 Jul 9; 460(7252):231-6.
    View in: PubMed
  13. Wesemann DR, Costenbader KH, Coblyn JS. Co-existing sarcoidosis, systemic lupus erythematosus and the antiphospholipid antibody syndrome: case reports and discussion from the Brigham and Women's Hospital Lupus Center. Lupus. 2009 Mar; 18(3):202-5.
    View in: PubMed
  14. Wesemann DR, Qin H, Kokorina N, Benveniste EN. TRADD interacts with STAT1-alpha and influences interferon-gamma signaling. Nat Immunol. 2004 Feb; 5(2):199-207.
    View in: PubMed
  15. Benveniste EN, Nguyen VT, Wesemann DR. Molecular regulation of CD40 gene expression in macrophages and microglia. Brain Behav Immun. 2004 Jan; 18(1):7-12.
    View in: PubMed
  16. Cobbs CS, Whisenhunt TR, Wesemann DR, Harkins LE, Van Meir EG, Samanta M. Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells. Cancer Res. 2003 Dec 15; 63(24):8670-3.
    View in: PubMed
  17. Wesemann DR, Benveniste EN. STAT-1 alpha and IFN-gamma as modulators of TNF-alpha signaling in macrophages: regulation and functional implications of the TNF receptor 1:STAT-1 alpha complex. J Immunol. 2003 Nov 15; 171(10):5313-9.
    View in: PubMed
  18. Wesemann DR, Dong Y, O'Keefe GM, Nguyen VT, Benveniste EN. Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages. J Immunol. 2002 Sep 1; 169(5):2354-60.
    View in: PubMed
  19. Nashimoto M, Wesemann DR, Geary S, Tamura M, Kaspar RL. Long 5' leaders inhibit removal of a 3' trailer from a precursor tRNA by mammalian tRNA 3' processing endoribonuclease. Nucleic Acids Res. 1999 Jul 1; 27(13):2770-6.
    View in: PubMed
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