Jennifer Alexander-Brett, M.D., Ph.D.

Assistant Professor
Internal Medicine
Pulmonary & Critical Care
Pathology and Immunology

Immunology Program
Developmental, Regenerative and Stem Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-273-1554

  • 314-273-1553

  • 8052

  • 10040 CSRB

  • jalexand@wustl.edu

  • Respiratory immunobiology, with particular interest in cytokine pathways associated with lung epithelial progenitors

Research Abstract:

My research focuses on respiratory immunobiology, with a particular interest in cytokine pathways associated with adult lung epithelial progenitor cells. My research background includes the application of structural biology, biochemistry and cell biology to immunological systems. I currently employ an array of techniques spanning model systems to molecular analyses to address the mechanistic basis of pulmonary diseases.

My initial mechanistic studies will build upon prior expertise developed during my postdoctoral study, involving the IL-33 cytokine system in chronic airway disease. IL-33 is a dual-functioning nuclear factor and secreted cytokine ("nucleokine") that has been found to participate in the development of inflammatory diseases involving virtually every organ system. I have identified lung progenitor epithelial cells as the source of increased IL-33 production in chronic airway disease, and further showed that cellular danger signals could induce release of IL-33 in vitro. Although we
have established that progenitor-derived IL-33 production is a key feature of airway disease pathogenesis, the mechanisms by which nuclear IL-33 is trafficked, processed and released from these cells in cytokine form are substantial knowledge gaps that have stymied efforts to target its function in disease. Accordingly, I plan to address the cellular mechanism by which airway disease-associated danger signals induce nuclear export, proteolytic processing and non-classical vesicular trafficking to release active IL-33 cytokine from progenitor epithelial cells. To address these questions, I employ a range of techniques including mouse models, 3D epithelial cell culture, live cell imaging, and structural, biochemical and molecular interaction studies. These mechanistic studies may yield more effective treatments for COPD, asthma and other respiratory diseases. Furthermore, as the relevance of IL-33 continues to expand to inflammatory disease in multiple organ systems, there is potential for an even broader impact of this work.

Future directions of the lab include development of progenitor cell-based assays to screen for new cytokine pathways that modulate lung progenitor cell function and application to pulmonary diseases that exhibit defective epithelial repair.

Selected Publications:

Byers DE* and Alexander-Brett J*, Patel AC, Agapov E, Dang-Vu G, Jin X, Wu K, You Y, Alevy Y, Girard JP, Stappenbeck TS, Patterson GA, Pierce RA, Brody SL, Holtzman MJ. Longterm IL-33-producing epithelial progenitor cells in chronic obstructive lung disease. J Clin Invest 2013; Sep;123(9):3967-82. (*authors contributed equally)

Martin AP, Alexander-Brett JM, Canasto-Chibuque C, Garin A, Bromberg JS, Fremont DH, Lira SA. The chemokine binding protein M3 prevents diabetes induced by multiple low doses of streptozotocin. J Immunol. 2007 Apr 1;178(7):4623-31.

Alexander-Brett JM, Fremont DH. Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor. J Exp Med. 2007 Dec 24;204(13):3157-72, PMCID: PMC2150966.

Alexander JM, Nelson CA, van Berkel V, Lau EK, Studts JM, Brett TJ, Speck SH, Handel TM, Virgin HW, Fremont DH. Structural basis of chemokine sequestration by a herpesvirus decoy receptor. Cell. 2002 Nov 1;111(3):343-56.

Alexander JM, Clark JL, Brett TJ, Stezowski JJ. Chiral discrimination in cyclodextrin complexes of amino acid derivatives: beta-cyclodextrin/N-acetyl-L-phenylalanine and N-acetyl-Dphenylalanine complexes. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5115-20.

Last Updated: 3/27/2017 4:11:49 PM

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