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 protein biochemistry to understand the mechanistic basis of pulmonary diseases. In my graduate research I gained expertise in structural biology, biochemistry and cell biology applied to immunological systems. Skills obtained during my postdoctoral studies include cellular immunology, development of respiratory disease animal models and analysis of human clinical specimens applied to study lung disease pathogenesis. The JAB lab currently applies this broad range of tools to explore mechanism in lung disease.

Historically, the lab has been interested in the molecular and cellular basis of IL-33 activation and signaling. This cytokine 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 has been the mechanism by which IL-33 is trafficked, processed and released from airway cells. We have recently discovered that IL-33 can be tonically secreted from lung epithelial cells in concert with a subset of endosomal-derived extracellular vesicles commonly referred to as ‘exosomes’. We are currently investigating the molecular basis of IL-33 recruitment to exosome biogenesis pathways, characterizing interacting partners with exosomes and investigating the impact of exosome secretion on IL-33 signaling. These studies have yielded special insight into other non-classically secreted cytokines relevant to pulmonary disease.

We have also expanded our interest in the study of exosomes as a novel mucosal signaling platform in pulmonary disease under homeostatic and disease conditions. We have considerable expertise in the biochemical and biophysical characterization of exosomes, manipulation of respective biogenesis pathways and characterization of exosomes derived from biospecimens. Our work to date has been informed by transcriptomic and proteomic profiling of exosomes from COPD specimens. Through this work we have identified potential novel disease pathways which may be amenable to targeting for therapeutic benefit.

We are also applying our current approach to investigate the role of epithelial derived exosomes in the mechanism of chronic lung allograft dysfunction (CLAD). There is increasing evidence that exosomes harbor antigens which can prime allo- and autoimmune pathways and drive progression of CLAD. We are also exploring the exosome-associated factors that signal dysfunctional epithelial repair as an early step in the pathologic sequence of CLAD. This project is actively recruiting clinical subjects and specimen biobanking is ongoing.


Mentorship and Commitment to Diversity Statement:
JAB lab is committed to wellness, diversity and inclusion.

Selected Publications:

Katz-Kiriakos E, Steinberg D, Kluender C, Osorio, O, BaroniaA, Newsom-Stewart, C, Katafiasz DM, Bailey KL, Byers, DE, Holtzman MJ, Brody SL, Miller MJ, Alexander-Brett J, IL-33 appropriates exosome trafficking for airway secretion in chronic airway disease. JCI Insight2021: 6(4): e136166.

Wu K, Kamimoto K, Zhang Y, Yang K, Keeler SP, Gerovac BJ, Agapov EV, Austin SP, Yantis Y, Gissy KA, Byers DE, Alexander-Brett J, Hoffman CM, Wallace M, Hughes ME, Crouch EC, Morris SA, Holtzman MJ, Basal-epithelial stem cells cross an alarmin checkpoint for post-viral lung disease. JCI 2021: 10.1172/JCI149336.

Trier AM, Mack MR, Fredman A, Tamari M, Ver Heul AM, Zhao Y, Guo CJ, Avraham O, Ford ZK, Oetjen LK, Feng J, Dehner C, Coble D, Badic A, Joshita S, Kubo M, Gereau RW 4th, Alexander-Brett J, Cavalli V, Davidson S, Hu H, Liu Q, Kim BS. IL-33 signaling in sensory neurons promotes dry skin itch. J All Clin Immunol 2021: 10.1016/j.jaci.2021.09.14.

Byers DE*, Alexander-Brett J*, Patel AC, Agapov EA, Dang-Vu G, Jin X, Wu K, You Y, Alevy YG, Brody SL, Pierce RA, Holtzman MJ, Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease, Journal of Clinical Investigation 2013: 123(9): 3967-82. *co-first authors. Cover article and featured in JCI Impact.

Last Updated: 5/23/2022 4:11:41 PM

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