micaela-fosdick@uiowa.edu
Mentor: Jon Houtman, Ph.D.
Lab Room: 2234 MERF
Lab Phone: 319-335-7597

Defining the Mechanisms of T-cell Receptor Signaling Inhibition by Glycerol Monolaurate

Glycerol Monolaurate (GML) is a 12 carbon chain compound, with a lauric acid linkage and glycerol head group antimicrobial agent that people come in contact with on a daily basis. It is on the Food and Drug Association’s Generally Recognized as Safe (FDA-GRAS) list and used commercially in food and many personal products. GML is also currently being tested in surgical dressings to prevent infection, as a treatment for bacterial vaginitis and toxic shock syndrome, and as a prophylactic for infections with HIV. However the effect of GML on human cells has not been fully investigated. With GML being used in clinical trials, it is important to understand how it will impact the immune response. T cells are essential for the regulation of the immune system and understanding how GML impacts T cells is especially significant in the context of the clinical use of GML. Recent work from our laboratory shows that GML inhibits T cell activation by disrupting lipid membrane dynamics and preventing Linker for Activation of T cells (LAT) cluster formation.

My studies aim to further investigate the mechanisms of GML inhibition. This project focuses on the effects of GML on T cell metabolism, and determining the structural components of GML necessary for it inhibiting activity. These studies contribute a mechanistic understanding of a novel class of immune modulating lipids, offer novel therapeutic applications of GML, and contribute to the development of new immunosuppressive derivatives of fatty acids with drug-like properties.



Zhang MS, Tran PM, Wolff AJ, Tremblay MM, Fosdick MG, Houtman JCD. Glycerol monolaurate induces filopodia formation by disrupting the association between LAT and SLP-76 microclusters. Sci Signal. 2018 May 1;11(528). pii: eaam9095. doi: 10.1126/scisignal.aam9095. PubMed PMID: 29717064.

Jensen IJ, Winborn CS, Fosdick MG, Shao P, Tremblay MM, Shan Q, Tripathy SK, Snyder CM, Xue HH, Griffith TS, Houtman JC, Badovinac VP. Polymicrobial sepsis influences NK-cell-mediated immunity by diminishing NK-cell-intrinsic receptor-mediated effector responses to viral ligands or infections. PLoS Pathog. 2018 Oct 31;14(10):e1007405. doi: 10.1371/journal.ppat.1007405. eCollection 2018 Oct. PubMed PMID: 30379932; PubMed Central PMCID: PMC6231673.