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During differentiation into eosinophils, eosinophil-lineage committed progenitors (EoPs) go through intermediate stages prior to reaching maturity. A number of stimulatory and inhibitory factors regulate these events. We have developed ex vivo culture methods to differentiate EoPs into mature eosinophils in order to identify novel regulators of eosinophil development (i.e. eosinophilopoiesis). We can also apply these methods to study genetic modifications of EoPs and the downstream effects on eosinophilopoiesis, as well as to generate large numbers of mature cells to investigate eosinophil effector functions.
Furthermore, eosinophils are exquisitely sensitive to their local microenvironment through expression of a plethora of receptors for cytokines, lipids and microbial products. Our high-yield culture methods allow for investigations into the regulation of these environmental sensors. These investigations could provide insight into eosinophil functional responses, such as the local degranulation and release of cytotoxic proteins, in tissues such as the lung in a patient with asthma or the esophagus in a patient with eosinophilic esophagitis (EoE).
Schollaert KL, Stephens MR, Gray JK, Fulkerson PC. Generation of eosinophils from cryopreserved murine bone marrow cells. PLoS One. 2014 Dec 31;9(12):e116141.
Fulkerson PC, Schollaert KL, Bouffi C, Rothenberg ME. IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation. J Immunol. 2014 Oct 15;193(8):4043-52.
Fulkerson PC, Rothenberg ME. Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov. 2013 Feb;12(2):117-29.
2013 ARTrust™ Faculty Development Award7/01/2013-6/30/2016Funding Agency: American Academy of Allergy, Asthma and Immunology (AAAAI)Project Title: Regulation of Eosinophil Progenitors by Toll-like ReceptorsPrincipal Investigator: Patricia C. Fulkerson, MD, PhD
K08 KAI093573A04/01/11-03/31/16Funding Agency: National Institutes of HealthProject Title: Role of Spi-C in Eosinophil Development and Functional ResponsesPrincipal Investigator: Patricia C. Fulkerson, MD, PhD
Recently, therapeutics that target eosinophils, by blocking specific steps of eosinophil development, migration or activation, have entered clinical testing and are having promising results.
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