Education & Training
- BS, Biochemistry, Mount Saint Mary’s University, Emmitsburg, MD 1999
- PhD, Chemistry, University of Maryland, Baltimore County (UMBC), Baltimore, MD, 2005
- NRSA Postdoctoral Fellow, University of Pennsylvania, Philadelphia, PA, 2010
Research Interest Summary
The overall scope of my research focuses on the formation, signaling and metabolism of bioactive fatty acids and lipid-sterols in lung and airway disease. For the last 10 years my lab has investigated electrophilic fatty acid signaling. Electrophilic fatty acids include nitro-fatty acids (NO2-FA) and oxo-fatty acids that contain either nitrogen dioxide or an α, β-unsaturated ketone. Nitro- and oxo-FA pleiotropically signal through the formation of Michael addition adducts with reactive nucleophilic cysteines found in redox regulatory transcription factors and enzymes to attenuate inflammation and metabolic dysregulation. NO2-FA modulate energy substrate utilization in innate immune cells to suppress intermediary metabolite signaling that promotes a pro-inflammatory polarization state. Because of the salubrious nature by which NO2-FA modulate redox signaling pathways associated with metabolism and inflammation, we are utilizing them to attune the systemic metabolic dysregulation that contributes to the pathology of obesity-associated asthma. This work is supported by a new R61HL157069. In these translational studies, we utilized untargeted metabolomics analysis and discovered that NO2-FA modulate systemic metabolite levels, some of which are formed through direct interaction with the microbiome.
This has led us to investigate the role of the microbiome and microbial-derived metabolites in obesity-associated asthma, independent of electrophilic fatty acid involvement. Thus, a new line of research has been established based on preliminary data in our murine model of obese allergic airway disease that demonstrates a role for bile acids in airway remodeling and resistance. These data are a result of a collaboration with Dr. Michelle Manni and Dr. Barbara Methé that has focused on the development of murine models to study obesity-associated asthma of which a manuscript was published (PMC8423735). In collaboration with Dr. Methé, who directs the Center for Medicine and the Microbiome, we are working to integrate metabolomics and microbiome data to elucidate microbial functions that promote a pro-asthmatic phenotype.
Wendell, Stacy Gelhaus; Baffi, Cindy; and Holguin, Fernando: Fatty acids, inflammation and asthma. Invited Review 2014. Journal of Allergy & Clinical Immunology 133(5):1255-1264, 2014. PMID: 24613565.
Snyder, Nathaniel W.; Golin-Bisello, Franca; Gao, Yang; Blair, Ian A.; Freeman, Bruce A.; and Wendell, Stacy Gelhaus: 15-oxoeicosatetraenoic acid is a 15-hydroxyprostaglandin dehydrogenase-derived electrophilic mediator of inflammatory signaling pathways. Chemico-Biological Interactions 234:144-53, 2015. PMID: 25450232.
Wendell, Stacy Gelhaus; Golin-Bisello, Franca; Wenzel, Sally; Sobol, Robert; Holguin, Fernando; and Freeman, Bruce: 15-hydroxyprostaglandin dehydrogenase generation of electrophilic lipid signaling mediators from hydroxy omega-3 fatty acids. Journal of Biological Chemistry 290(9):5868-5880, 2015. PMID: 25586183.
Delmastro-Greenwood, Meghan; Hughan, Kara S.; Vitturi, Dario A.; Salvatore, Sonia R.; Grimes, George; Potti, Gopal; Shiva, Sruti; Schopfer, Francisco J.; Gladwin, Mark T.; Freeman, Bruce A.; and Wendell, Stacy Gelhaus: Nitrite and nitrate-dependent generation of fatty acid nitroalkenes. Free Radical Biology & Medicine, 89:333-341, 2015. PMID: 26385079.
Wendell, Stacy G.; Fan, Hao; and Zhang, Cheng. G protein-coupled receptors in asthma therapy: pharmacology and drug action. Pharmacological Reviews. 72:1-49, 2020. PMID 31767622.
Manni, Michelle L.; Heinrich, Victoria A.; Buchan, Gregory J.; O`Brien, James P.; Uvalle, Crystal; Cechova, Veronika; Koudelka, Adolf; Ukani, Dharti; Rawas-Qalaji, Mohamad; Oury, Tim D.; Hart, Renee; Ellgass, Madeline; Mullett, Steven J.; Fajt, Merritt L.; Wenzel, Sally E.; Holguin, Fernando; Freeman, Bruce A.; and Stacy G. Wendell. Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma. Scientific Reports, 11: 17788, 2021. PMID: 34493738.
Snyder, Nathaniel W.; O’Brien, James P.; Singh, Bhupinder; Buchan, Gregory; Arroyo, Alejandro D.; Liu, Xiaojing; Bostwick, Anna; Varner, Erika L.; Angajala, Anusha; Sobol, Robert W.; Blair, Ian A.; Mesaros, Clementina; and Stacy G. Wendell. Primary saturation of α,β-unsaturated carbonyl containing fatty acids does not abolish electrophilicity. Chemico-Biological Interactions, December 2021. PMID: 34634267.
O’Donnell, Valerie B.; Schebb, Nils H.; Milne, Ginger L.; Murphy, Michael P.; Thomas, Christopher P.; Steinhilber, Dieter; Wendell, Stacy G.; Kühn, Hartmut; Jakkobsen, Per-Johan; Blair, Ian; Murphy, Robert C.; Freeman, Bruce A.; Brash, Alan R.’ FitzGerald, Garret A. Failure to apply standard limit-of-detection or limit-of-quantitation criteria to specialized pro-resolving mediator analysis incorrectly characterizes their presence in biological samples. https://zenodo.org/record/5766267#.YbCfd6DLdpQ.