Dr. Heller’s research focuses on the immunobiology of macrophages and how they affect diseases that have an inflammatory basis, including obesity, cardiovascular disease and cancer. Although alternatively activated and classically activated macrophage phenotypes can be useful designations, it is apparent that macrophages exist along a phenotypic spectrum and may have the capacity to convert their phenotypes. Dr. Heller's group actively engages in this exciting new area of macrophage immunobiology.
Specifically, her laboratory focuses on the role of IL-4/IL-13 signaling in asthma and allergic disease. She is interested in the basic mechanisms of signaling: from the biology, signal transduction, and regulation of the IL-4/IL-13 receptor to the role of alternatively activated macrophages or "M2" macrophages in the pathogenesis of allergic inflammation. She focuses particularly on the consequences of chronic or dysregulated M2 macrophage responses and how to prevent or interrupt these processes.
Current projects are focused on uncovering the molecular mechanisms that underpin sex differences in asthma and determining how sex affects asthma in humans. She and her team use a variety of techniques, including molecular and cellular biology, biochemistry, mouse models, cultured cell lines, and human patient samples to uncover cellular and molecular pathways that will be relevant targets for human clinical benefit.
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LaPorte SL, Juo, ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC. Molecular and Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4/13 System. Cell, 2008 Jan 25; 132: 259-272. PMC2265076
Heller NM, Qi X, Junttila IS, Shirey KA, Vogel SN, Paul WE, Keegan AD. Type I IL-4Rs selectively activate IRS-2 to induce target gene expression in macrophages. Sci Signaling. 2008 Dec 23, 1(51): ra17. PMC2739727
McCormick SM, Gowda N, Fang JX, Heller NM. Suppressor of Cytokine Signaling (SOCS)1 Regulates IL-4-Activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome. J Biol Chem. 2016 Aug 9. pii: jbc.M116.746164. [Epub ahead of print]. PMCID: PMC5034051
Warren KJ, Fang XJ, Gowda NM, Thompson JJ, Heller, NM. The TORC1-Activated Proteins, P70S6K and GRB10, Regulate IL-4 Signaling and M2 Macrophage Polarization by Modulating Phosphorylation of Insulin Receptor Substrate-2. J Biol Chem. 2016 Oct 14. pii: jbc.M116.756791. [Epub ahead of print]. PMCID: 27742835. PMC5122764
Keselman A, Fang JX, White PB, Heller NM. Estrogen signaling contributes to sex differences in macrophage polarization during asthma. J Immunol, 2017 Sep 1;199(5):1573-1583