Krager, KJ, Sarkar, M, Twait, EC, Lill, NL, Koland, JG. A novel biotinylated lipid raft reporter for electron microscopic imaging of plasma membrane microdomains. J Lipid Res 53(10):2214-2225, 2012. PMID: 22822037
Visser Smit, GD, Place, TL, Cole, SA, Clausen, KA, Vemuganti, S, Zhang, G, Koland, JG, Lill, NL. Cbl controls EGFR fate by regulating early endosome fusion. Science Signaling, 2(102), ra86 [DOI: 10.1126/scisignal.2000217], 2009.
Cao, XR, Lill, NL, Shi, PP, Shan, H, Qu, J, Sweezer, EM, Place, T, Kirby, PA, Shao, D, Kinney, TS, Volk, KA, Williamson, RA, Stokes, JB, and Yang, B. Inactivating Grb10 prevents growth retardation and rescues perinatal lethality of Nedd4-1 null mice. Science Signaling, 1(38), Published online Sep. 23, 2008. †, equal contribution to this work
Stern, KA, Place, TL, and Lill, NL. EGF and amphiregulin differentially regulate Cbl recruitment to endosomes and EGF receptor fate. Biochem J, 410:585-594, 2008. Published online Nov. 28, 2007, doi:10.1042/BJ20071505.
Stern, KA, Visser Smit, GD, Place, TL, Winistorfer, S, Piper, RC, and Lill, NL.: EGF receptor fate is controlled by Hrs tyrosine phosphorylation sites that regulate Hrs degradation. Mol Cell Biol, 27:888-898, 2007. Published online Nov. 13, 2006.
Visser, GD and Lill, NL.: The Cbl RING finger C-terminal flank controls epidermal growth factor receptor fate downstream of receptor ubiquitination. Exp Cell Res, 311:281-293, 2005.
Lill, NL, Douillard, P, Awwad, R, Ota, S, Lupher, ML Jr, Miyake, S, Meissner-Lula, N, Hsu, V, and Band, H. The evolutionarily conserved amino terminal region of Cbl is sufficient to enhance down-regulation of the epidermal growth factor receptor. J Biol Chem 275:367-377, 2000.
Research in my laboratory focuses on negative regulation of receptor-mediated signaling. One member of the ErbB receptor family, the epidermal growth factor receptor (EGFR), is negatively regulated by its recruitment of the signaling protein Cbl. Cbl associates with activated EGFR, undergoes tyrosine phosphorylation, and colocalizes with EGFR in tubulovesicular structures of the endocytic pathway. I and others have shown that overexpression of Cbl enhances EGFR downregulation from the cell surface, recruitment into the endocytic trafficking pathway, and degradation. Although Cbl functions as a component of the ubiquitylation machinery that targets proteins for proteasome-mediated degradation, the bulk of EGFR degradation occurs in the lysosome. Studies in my laboratory are aimed at defining the mechanism for Cbl-mediated enhancement of EGFR lysosomal degradation.Ongoing work addresses the following questions: (1) which Cbl structural domains or motifs are critical for enhanced EGFR downregulation and degradation?; (2) can these domains be used as targeting motifs to degrade other oncogenic receptor tyrosine kinases?; and (3) which protein-protein interactions are required to route activated EGFR to the lysosome, and how are they affected by Cbl overexpression, mutation, or knock-down? The laboratory utilizes a variety of genetic, biochemical, and cell biological techniques to address these questions. Exciting ongoing work involves live cell imaging of endocytic fusion events.