Possible Rotation Projects:
Altered metabolism (host and microbial) that promotes obesity-associated asthma
Bioactive fatty acid regulators of immune cell metabolism and inflammatory status
Training Technologies Used:
- high resolution mass spectrometry (metabolomics, lipidomics, and proteomics)
- biochemical techniques (PCR, western, ELISA, flow cytometry
- 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
Stevenson, Emily R.; O`Brien, James P.; Manuel, Allison M.; Uvalle, Crystal E.; Buchan, Gregory J.; Mullett, Steven J.; Lockwood, Karina; Suber, Tomeka; Freeman, Bruce A.; and Stacy L. Gelhaus. Nitro-oleic acid attenuates pro-inflammatory metabolic signaling mediators linked to effector function in macrophage. Front Physiol, Oct 16:26:1426102, 2025. PMID: 41178983, PMCID: PMC12572803.
Koudelka A, Buchan GJ, Cechova V, O'Brien JP, Liu H, Woodcock SR, Mullett SJ, Zhang C, Freeman BA, Gelhaus SL. Lipoxin A(4) yields an electrophilic 15-oxo metabolite that mediates FPR2 receptor-independent anti-inflammatory signaling. J Lipid Res, Jan 66(1):100705, 2025. PMID: 39566850. PMCID: PMC11729656.
O’Donnell, Valerie B.; Schebb, Nils H.; Milne, Ginger L.; Murphy, Michael P.; Thomas, Christopher P.; Steinhilber, Dieter; Gelhaus, Stacy L.; Kühn, Hartmut; Gelb, Michael, 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. Nature Communications, Nov 9;14(1):7172, 2023. PMID: 37945602, PMCID: PMC10636151.
Heinrich, Victoria A.; Uvalle, Crystal; Manni, Michelle L.; Li, Kelvin; Mullett, Steven J.; Donepudi, Sri Ramya; Clader, Jason; Fitch, Adam; Ellgass, Madeline; Cechova, Veronika; Holguin, Bruce A. Freeman, Fernando; Methé, Barbara A.; Morris, Alison; and Stacy L. Gelhaus. Meta-omics profiling of the gut-lung axis illuminates metabolic networks and host-microbial interactions associated with elevated lung elastance in a murine model of obese asthma. Frontiers in Microbiomes, May, 2023.doi.10.3389/frmbi.2023.1153691. PMCID: PMC10249466
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.
