John G. Koland, PhD


Associate Professor of Pharmacology
Associate Professor of Internal Medicine

Contact Information

Primary Office: 2-550 Bowen Science Building
Iowa City, IA 52242
Phone: 319-335-6508

Lab: 2-551 Bowen Science Building
Iowa City, IA 52242
Phone: 319-335-6551



BS, Chemistry, University of Minnesota
PhD, Chemistry, University of Illinois

Post Doctorate, Chemistry, Cornell University

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Molecular and Cellular Biology

Research Summary

Research in the Koland laboratory focuses upon the signaling events elicited by members of the epidermal growth factor (EGF) receptor family (ErbB/HER family receptors). ErbB family receptors are among a larger group of receptors possessing intrinsic protein tyrosine kinase activity that is activated upon binding of polypeptide growth factors. ErbB receptors and their associated growth factor ligands play crucial roles in human cancer, and in the context of breast cancer, they are important diagnostic markers and the targets of new therapeutic agents. The Koland laboratory is investigating ErbB receptor signaling in mammary tumor cells by use of biochemical and biophysical approaches. One research initiative addresses the molecular mechanisms by which the intracellular protein tyrosine kinase domain of the EGF receptor is regulated by binding of growth factor to the receptor extracellular domain. Here the laboratory has developed novel fluorescent spectroscopic methods by which structural changes associated with receptor activation and phosphorylation can be detected. With these methods Dr. Koland's laboratory has demonstrated that phosphorylation of the receptor C-terminal domain alters its conformation and effects its displacement relative to the catalytic site. These findings are consistent with a model in which the C-terminal phosphorylation domain in the basal state interacts with the catalytic core of the kinase to inhibit its activity. In this model, phosphorylation of the C- terminal domain induces structural changes that relieve this inhibitory interaction and result in kinase activation. A more recent initiative explores how ErbB family members are spatially organized in the cell membrane at the sub-light microscopic level, and how this spatial microorganization might be perturbed in cancer cells. Here the laboratory seeks to determine whether ErbB receptors are confined to membrane microdomains of specific biochemical composition and how membrane microenvironment impacts upon receptor signaling. Approaches used include fluorescence microscopy and electron microscopy (EM). Preliminary EM studies indicate that ErbB receptors are in breast cancer cell membranes indeed localized in submicroscopic domains consistent with the size of lipid rafts.

Selected Publications

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Koland J.  Coarse-grained molecular simulation of epidermal growth factor receptor protein tyrosine kinase multi-site self-phosphorylation.  PLoS Comput Biol.  2014. 10(1):e1003435.

Krager K, Sarkar M, Twait E, Lill N, Koland J.  A novel biotinylated lipid raft reporter for electron microscopic imaging of plasma membrane microdomains..  Journal of lipid research.  2012 October. 53(10):2214-25.

Vaught D, Stanford J, Young C, Hicks D, Wheeler F, Rinehart C, Sanchez V, Koland J, Muller W, Arteaga C, Cook R.  HER3 is required for HER2-induced preneoplastic changes to the breast epithelium and tumor formation..  Cancer research.  2012 May. 72(10):2672-82.

Lee N, Hazlett T, Koland J.  Structure and dynamics of the epidermal growth factor receptor C-terminal phosphorylation domain..  Protein science : a publication of the Protein Society.  2006 May. 15(5):1142-52.

Lee N, Koland J.  Conformational changes accompany phosphorylation of the epidermal growth factor receptor C-terminal domain..  Protein science : a publication of the Protein Society.  2005 November. 14(11):2793-803.

Monick M, Cameron K, Staber J, Powers L, Yarovinsky T, Koland J, Hunninghake G.  Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis..  The Journal of biological chemistry.  2005 January. 280(3):2147-58.

Date Last Modified: 06/06/2016 - 13:17:48