Kushner, Erich - University of Denver - Department of Biological Sciences

个人简介

2004 B.S., Cellular and Molecular Biology - Fort Lewis College - Durango, CO 2010 Ph.D., Integrative Physiology - University of Colorado - Boulder, CO 2010-2016, Postdoctoral Fellow, University of North Carolina - Chapel Hill, NC

研究领域

Our lab explores how blood vessels function in development and disease. A single person's blood vessels will wrap around Earth four times if stretched end-to-end. With this in mind, it is no surprise that blood vessels are absolutely required for survival and are the first organ system to form embryonically. In a process called angiogenesis, endothelial cells, the most basic unit of blood vessels, proliferate, migrate and collectively move to form a complex and expansive vasculature system allowing nutrient penetration to every cell in our bodies. How individual endothelial cells collectively orchestrate such morphogenic feats in a reproducible and stereotyped fashion is unclear. More specifically, how endothelial cells harness intrinsic cytoskeletal programs to move, polarize, communicate with their neighbors and engage their immediate surroundings during angiogenesis is not very well understood, particularly in disease states such as cancer. To better understand angiogenic processes, our laboratory uses state-of-the-art microscopy techniques and live-imaging, using fluorescently-tagged versions of cytoskeletal regulatory protiens in vitro and in vivo. This allows us to examine cell behavior and cellular processes during dynamic events of morphogenesis, such as lumen formation. In addition to cell culture and organotypic models of angiogenesis, our lab heavily relies on zebrafish as an experimental platform of vascular development. Zebrafish are fantastic model organisms for blood vessel research as they have extra-uterine development and are completely transparent early in life, allowing for imaging of complex morphogenetic events in vivo. Importantly, this model system also allows us to leverage novel CRISPR/Cas9 technologies and other genetic approaches for genomic editing, creation of light-inducible gene expression systems, conditional tissue-specific gene knockouts and other perturbations for dissecting the contribution of various signaling circuits to angiogenesis during development or in disease-related vascular dysfunction. We are currently exploring how endothelial cells use cell-cell adhesions called tight junctions, to inform rearrangement of the actin and microtubule cytoskeleton for cell polarization during vascular network formation. We are genetically ablating cell contractile machinery components and/or specific Rho GTPase superfamily protiens using CRISPR-based homologous recombination targeting in zebrafish to determine how these program influence junctional integrity and cell polarity. In a separate project, we are investigating how a family of proteins called synaptotagmin-like proteins, contribute to lumen formation by helping to specify apical-basal polarity in endothelial cells during lumenigenesis. To do this we are again using genomic targeting techniques such as endogenous protein tagging coupled with advanced light microscopy to best understand the "when and "where" of synaptotagmin's involvement in endothelial lumen formation during development. Overall, our research is dedicated to understanding how blood vessels form and how these processes go wrong in various disease states, for advancement of next-generation therapies.

近期论文

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Yu Z, Mouillesseaux KP, Kushner EJ, Bautch VL. Tumor-Derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-Duplication. PLoS One. 2016 Dec 15;11(12):e0168334. doi: 10.1371/journal.pone.0168334. PMID: 2797777 Mouillesseaux K., Wiley D., Saunders L., Wylie L., Kushner E., Chong D., Citrin K., Barber A., Park Y., Kim J., Samsa L.A., Kim J., Liu J., Jin W., Bautch V. (2016). Notch Regulates BMP Responsiveness and Lateral Branching in Vessel Networks via SMAD6. Nature Communications. (Accepted). Kushner EJ, LS Ferro, Z Yu and VL. Bautch. Excess Centrosomes Perturb Dynamic Endothelial Cell Repolarization During Blood Vessel Formation. Mol Biol Cell. 2016 Jun 15;27(12):1911-20. Epub 2016 Apr Wright CE, EJ Kushner, Q Du, and VL Bautch. LGN Directs Interphase Endothelial Cell Behavior via the Microtubule Network. PLoS One. 2015 Sep 23;10(9):e0138763. PMID:26398908 KR. Klein, NO Karpinich, ST Espenshied, HH Willcockson, WP Dunworth, SL. Hoopes, EJ Kushner, VL Bautch, and KM Caron. Decoy Receptor CXCR7 Modulates Adrenomedullin-Mediated Cardiac and Lymphatic Vascular Development. Dev Cell. 2014 Sep 8;30(5):528-540. PMID:25203207 Kushner EJ, LS Ferro, JY Liu, JR Durrant, SL Rogers, AC Dudley, VL Bautch. Excess centrosomes disrupt endothelial cell migration via centrosome scattering. J Cell Biol. 2014 Jul 21;206(2):257-72. PMID:25049273 Charpentier MS, Christine KS, Amin NM, Dorr KM, Kushner EJ, Bautch VL, Taylor JM, Conlon FL. CASZ1 promotes vascular assembly and morphogenesis through the direct regulation of an EGFL7/RhoA-mediated pathway. Dev Cell. 2013 Apr 29;25(2):132-43. PMID:23639441 Kushner EJ, Bautch VL. Building blood vessels in development and disease. Curr Opin Hematol. 2013 May;20(3):231-6.Review. PMID:23567339 Diehl KJ, Weil BR, Westby CM, MacEneaney OJ, Kushner EJ, Greiner JJ, DeSouza CA. Effects of Endothelin-1 on Endothelial Progenitor Cell Function. Clin Chem Lab Med. 2012 Feb 1;50(6):1121-4. PMID:22706256 Weil BR, Kushner EJ, Diehl KJ, Greiner JJ, Stauffer BL, DeSouza CA. CD31+ T cells, Endothelial Function and Cardiovascular Risk. Heart Lung Circ. 2011 Oct;20(10):659-62. Epub 2011 Jul 20. Kushner EJ, Weil BR, MacEneaney OJ, Morgan RG, Mestek ML, Van Guilder GP, Diehl KJ, Stauffer BL, DeSouza CA.Human Aging and CD31+ T-cell Number, Migration, Apoptotic Susceptibility, and Telomere Length. J Appl Physiol. 2010 Dec;109(6):1756-61. PMCID: PMC3006402 MacEneaney OJ, DeSouza CA, Weil BR, Kushner EJ, Van Guilder GP, Mestek ML, Greiner JJ, Stauffer BL. Prehypertension and Endothelial Progenitor Cell Function. J Hum Hypertens. 2011 Jan;25(1):57-62. PMCID: PMC:2895004 MacEneaney OJ, Kushner EJ, Westby CM, Cech JN, Greiner JJ, Stauffer BL, DeSouza CA. Endothelial Progenitor Cell Function, Apoptosis, and Telomere Length in Overweight/Obese Humans. Obesity (Silver Spring). 2010 Sep;18(9):1677-82. Kushner E, GL Hoetzer, OJ MacEneaney, JJ Greiner, JN Cech, BL Stauffer, CA DeSouza. Aging and Endothelial Progenitor Cell Release of Proangiogenic Cytokines. Age Ageing. 2010 Mar;39(2):268-72. PMCID: PMC2842112 Klawitter J, J Klawitter, E Kushner, KR Jonscher, J Bendrick-Peart, U Christians, V Schmitz, Association of Immunosuppressant-Induced Protein Changes in the Rat Kidney with Changes in Urine Metabolite Patterns: A Proteo-Metobonomic Study. J Proteome Res. 2010 Feb 5;9(2):865-75. Kushner EJ, RG Morgan, AM Van Engelenburg, OJ MacEneaney, GP Van Guilder, CA DeSouza. CD31+ T Cells Represent a Functionally Distinct Vascular T Cell Phenotype. Blood Cells, Molecules and Diseases. 2010 Feb 15;44(2):74-78. MacEneaney OJ, EJ Kushner, GP Van Guilder, JJ Greiner, BL Stauffer, CA DeSouza. Endothelial Progenitor Cell Number and Colony-Forming Capacity in Overweight and Obese Adults. International Journal of Obesity. Feb 2009;33(2):219-225. PMC2643316