Zhang, Michael

Michael Zhang

Address: 2234B MERF
Phone: (319) 335-7597
Email: michael-zhang@uiowa.edu

Mentor: Jon C. Houtman, PhD

Undergraduate Institution: University of Iowa

Year Entered Into Program: 2013

Research Description

Glycerol Monolaurate (GML) is a naturally occurring fatty acid molecule and antimicrobial agent.  GML suppresses the growth and virulence of numerous gram positive and gram negative bacteria, fungi, and enveloped viruses.  GML is on the FDA’s Generally Recognized as Safe list (GRAS) and is incorporated in various products such as deodorants, lotions, and cosmetics.  It is also widely available as a homeopathic supplement, and is extensively used as a food preservative and emulsifier. Topical GML is being tested as a treatment and/or preventative measure for Toxic Shock Syndrome, HIV transmission, and surgical site infections.  Thus, GML is an effective antimicrobial that comes in regular contact with the general public through its extensive commercial and therapeutic uses.Interestingly, GML suppresses mitogen induced lymphocyte proliferation and inositol triphosphate production, suggesting that GML has immunomodulatory functions.  However, how GML treatment affects the full T cell activation response from signaling events to effector functions is not well understood.  In addition, the mechanism behind how GML mediates suppressed T cell activation is completely unknown.

My thesis project focuses on mechanistically examining if GML affects the signaling, metabolism, and functional output of human primary T cells.  We found that GML potently altered order and disorder dynamics in the plasma membrane that resulted in reduced membrane localized clustering of the proteins LAT, PLC-γ, and AKT, events integral for proper T cell receptor (TCR) signal propagation.  Altered membrane signaling events induced selective inhibition of TCR-induced phosphorylation of SLP-76, regulatory P85 subunit of PI3K, and AKT as well as abrogated calcium influx. In addition to signaling defects, GML treated cells have profoundly altered metabolism profiles characterized by suppressed oxidative phosphorylation and increased glycolysis.  Functionally, GML treatment potently reduced TCR-induced production of the cytokines IL-2, IFN-γ, TNF-α, and IL-10 and decreased cellular adhesion via defective actin polymerization. Our data reveal that the widely used anti-microbial agent GML alters the lipid dynamics of human T cells, leading to their defective signaling, metabolism, and function.


Hassan IH, Zhang MS, Powers LS, Shao JQ, Baltrusaitis J, Rutkowski DT, Legge K, Monick MM. Influenza A viral replication is blocked by inhibition of the inositol-requiring enzyme 1 (IRE1) stress pathway. J Biol Chem. 2012 Feb 10;287(7):4679-89. doi: 10.1074/jbc.M111.284695. Epub 2011 Dec 22. PubMed PMID: 22194594; PubMed Central PMCID: PMC3281634.

Monick MM, Powers LS, Walters K, Lovan N, Zhang M, Gerke A, Hansdottir S, Hunninghake GW. Identification of an autophagy defect in smokers' alveolar macrophages. J Immunol. 2010 Nov 1;185(9):5425-35. doi: 10.4049/jimmunol.1001603. Epub 2010 Oct 4. PubMed PMID: 20921532; PubMed Central PMCID: PMC3057181.