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Bryan Copple, Ph.D.

Associate Professor, Pharmacology & Toxicology

B403 Life Sciences
1355 Bogue Street
East Lansing, MI 48824

Email: copple@msu.edu

Phone: (517) 884-6691 | Fax: (517) 353-8915 | Location:  B403 Life Sciences

Fields of Interest: The research in my laboratory is focused on understanding the role of the immune system and hypoxia in the development of liver disease.

    • 1988-1991 - B.S., Biology, Morningside College, Iowa
    • 1991-1997 - Ph.D., Pharmacology, University of Nebraska Medical Center
    • 1997-1998 - Research Associate, Pharmacology & Toxicology, Michigan State University
    • 1998-1999 - Research Associate, Multidisciplinary Training in Environmental Toxicology, Michigan State University
    • 1999-2001 - NRSA Postdoctoral Fellow, Pharmacology & Toxicology, Michigan State University
    • 2001-2003 - Research Associate, Pharmacology & Toxicology, Michigan State University
    • 2003-2010 - Assistant Professor, Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center
    • 2010-2011 - Associate Professor, Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center
    • 2011-present - Associate Professor, Pharmacology & Toxicology, Michigan State University

    Research Synopsis

    The overall research focus in the Copple lab is to uncover the mechanisms regulating immune cell function during tissue injury and repair.  Elucidating these mechanisms is important, as studies have revealed that dysregulated immunity contributes to the development of diverse diseases including cancer, neurological disorders, cardiovascular disease, and organ fibrosis, among others.  Accordingly, better insight into the mechanisms controlling immune cell function during tissue injury and repair could reveal how these processes become dysregulated leading to disease. 

    Our laboratory utilizes a variety of approaches to investigate immune cell function, including cell culture with primary cells isolated from mice and patients and in vivo studies utilizing genetically modified mice.  We couple these basic mechanistic studies with drug discovery approaches to identify drugs and/or chemicals that restore immune cell function and drive reversal of disease.

    Specific Projects

    Elucidating the Mechanisms Controlling Monocyte/Macrophage Phenotype Switching during Fibrosis and Cancer

    Fibrosis: Fibrosis (i.e., excess matrix deposition or a scar) ishigh-throughput drug screening to identify fibrosis reversing drugs - image a serious consequence of chronic tissue injury that occurs in the lungs, liver, and other organs.  If left unchecked, fibrosis can ultimately result in organ failure and often death.  Currently, there are no drugs to treat fibrotic disorders.  Our laboratory is investigating whether pharmacological reprograming of myeloid cells (monocytes, macrophages) could reverse fibrosis and restore organ function.  The rationale for this is that after tissue injury, monocytes are recruited from the blood to the damaged tissue where they produce factors that promote deposition of extracellular matrix.  As tissue repair nears completion, the recruited monocytes mature into macrophages producing a phenotype that degrades the excess matrix.  During chronic tissue injury, this shift in phenotype fails resulting in the persistent deposition of matrix leading to fibrosis.  Our studies are focused on elucidating the mechanisms controlling “phenotype switching” during fibrosis reversal, so that this process can triggered pharmacologically.  To complement these studies, we are conducting a high-throughput drug screen to identify drugs and/or chemicals that stimulate this conversion (Figure 1).  Through this work, we have identified a number of novel pathways that are important for regulating monocyte/macrophage phenotype during tissue injury and repair.  

    Awards

    Morningside College

    • Zeta Sigma Scholastic Honor Society, 1991
    • Graduated Magna Cum Laude, 1991

    University of Nebraska Medical Center

    • University of Nebraska Medical Center Regents Tuition Fellowship, 1992-96
    • Pharmaceutical Sciences Training Program Travel Award, 1993
    • Herbert L. Davis Scholarship in Pharmacology, 1994 (awarded for the best Pharmacology Graduate Student oral presentation at the Annual Student Research Forum at the University of Nebraska Medical Center)
    • Thomas Jefferson Ingenuity Award, 1997 (awarded to the top graduating Graduate Student at the University of Nebraska Medical Center)

    University of Kansas Medical Center

    • Travel Award, 2006, 2008, 2009
    • Thomas G. Noffsinger, Ph.D. Investigator Award, 2006
    • Kansas IDeA network of Biomedical Research Excellence Faculty Scholar Award, 2008

    Michigan State University

    • Postdoctoral Fellowship, Multidisciplinary Training in Environmental Toxicology Training Grant, 1998-99
    • NIH Individual National Research Service Award, Pharmacology and Toxicology, 1999-2001

    Achievements

    • Presidential Poster of Distinction, American Association for the Study of Liver Disease Annual Meeting, Boston, MA, 2006, 2009
    • Discussion Panel entitled “Mentoring Teams: Guides, Allies, and Advocates,” Educator Series, Office of Professional Development and Academic Affairs at the University of Kansas Medical Center, 2007
    • Served as Secretary for the University of Kansas Medical Center Chapter of Sigma Xi, 2006-08
    • Served as the President-Elect for the University of Kansas Medical Center, Chapter of Sigma Xi, 2008-09

    Committees

    University of Kansas Medical Center

    • Pharmacology, Toxicology, and Therapeutics, Web-site Committee, 2005
    • Pharmacology, Toxicology, and Therapeutics, Student Expectations Committee, 2005
    • Pharmacology, Toxicology, and Therapeutics, Summer Anything Goes Seminar series, Chair, 2006
    • Pharmacology, Toxicology, and Therapeutics, COBRE Histology Core Facility Director, 2007-2011
    • Member, Internal Advisory Board for the University of Kansas Medical Center Liver Center, 2007-2011
    • Representative for the Department of Pharmacology, Toxicology, and Therapeutics, School of Medicine Faculty Council, 2009-2011

    Editorial Boards

    • Liver International (official journal of the International Association for the Study of the Liver)

    National & International Society Committees

    • Ad hoc Review Group, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2009

    Society of Toxicology

    • Member, Discussion Panel, “Career Resource and Development Seminar: Life After Your Post-doc: Advice on Finding and Landing a Job,” 2006 Annual Meeting, San Diego, CA
    • Academic Advisor Facilitator, Undergraduate Education Program, What is Graduate School and What Can I Expect, 2010, Salt Lake City

    Central States Toxicology Annual Meeting (Chapter of the Society of Toxicology)

    • Poster Presentation Judge, University of Iowa, Iowa City, IA, 2007-2009
    • Secretary/Treasurer, 2008-present

    Other Activities

    Book Reviewer

    • Phillips MI, “Methods in Molecular Medicine: Antisense Therapeutics,” 2nd edition, Totowa: Humana Press, 2006
    • Chadwick DJ, Good J, “Signaling Pathways in Acute Oxygen Sensing,” Chichester: John Wiley and Sons Ltd, 2006

    Full list of publications at MSU Scholars

    • Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice. Yang M, Ramachandran A, Yan HM, Woolbright BL, Copple BL, Fickert P, Trauner M, Jaeschke H. Toxicol Lett. 2014 Jan 13;224(2):186-95. doi: 10.1016/j.toxlet.2013.10.030. Epub 2013 Nov 2.PMID: 24188933 [PubMed - in process]
    • Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. Allen K, Jaeschke H, Copple BL. Am J Pathol. 2011 Jan;178(1):175-86. doi: 10.1016/j.ajpath.2010.11.026. Epub 2010 Dec 23. PMID: 21224055 [PubMed - indexed for MEDLINE] Free PMC Article
    • Effect of bile duct ligation on bile acid composition in mouse serum and liver. Zhang Y, Hong JY, Rockwell CE, Copple BL, Jaeschke H, Klaassen CD. Liver Int. 2012 Jan;32(1):58-69. doi: 10.1111/j.1478-3231.2011.02662.x. Epub 2011 Oct 17. PMID: 22098667 [PubMed - indexed for MEDLINE] Free PMC Article
    • Oxidative stress and the pathogenesis of cholestasis. Copple BL, Jaeschke H, Klaassen CD. Semin Liver Dis. 2010 May;30(2):195-204. doi: 10.1055/s-0030-1253228. Epub 2010 Apr 26. Review. PMID: 20422501 [PubMed - indexed for MEDLINE]