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

  • 10040 CSRB

  • jalexand@wustl.edu

  • https://sites.wustl.edu/jablab/

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

Research Abstract:

My lab integrates mucosal immunology, epithelial stem cell biology and biochemistry to understand the mechanistic basis of pulmonary diseases. My graduate research background includes structural biology, biochemistry and cell biology applied to immunological systems. My postdoctoral experience includes the use of cellular immunology, mouse models and clinical samples in translational studies of lung disease pathogenesis. The JAB lab applies these tools to investigate perturbations in adult epithelial stem cell homeostasis that occur in lung diseases exhibiting dysregulated epithelial growth or stem cell failure.

One major area of interest for the lab involves the cytokine IL-33, which is produced by expanded lung epithelial stem cells in chronic airway disease, and is a key mediator of type-2 inflammation in COPD and asthma. A major knowledge gap in the field of IL-33 biology is the mechanism by which nuclear IL-33 is trafficked, processed and released from these cells. We are currently taking a multidisciplinary approach to dissect the non-classical IL-33 secretory pathway in the context of COPD and asthma. This effort has yielded novel mediators and interacting proteins and has illuminated a previously unrecognized form of airway secretion with broad implications for epithelial biology. Ongoing work will investigate the structural basis of IL-33 interactions with relevant binding partners and the potential for these intermediates to serve as biomarkers or therapeutic targets in chronic airway disease.

In a related project, our lab has become interested in the role of lung-derived extracellular vesicles (EVs, commonly referred to as ‘exosomes’) in airway disease pathogenesis. We have recently gained considerable expertise in the biochemical and biophysical characterization of EVs in the context of pulmonary disease. Our current approach involves a combined transcriptomic and proteomic comparison of diseased and control vesicle populations to uncover the role of EV-mediated signaling in the pathogenesis of chronic airway disease. Future studies of altered transcripts and proteins will focus on factors regulating cellular uptake and impact of EV signaling on target cells.

I am also interested in expanding our current approach to the area of my clinical focus, lung transplantation. We are exploring the factors that contribute to dysregulated epithelial stem cell growth that ultimately leads to development of chronic lung allograft dysfunction. Future studies will be focused on the role of specific growth factor pathways in this process.

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: 8/16/2019 9:09:19 AM

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