Mark D. Zabel
Assistant Professor
Phone: 491-1455
Fax: 491-0603
Email:
Mark.Zabel@ColoState.EDU
Office: 227 Pathology Building
Degrees
BA, Loyola University of Chicago, 1990
MS, Southern Illinois University, 1995
PhD, University of Utah, 2001
Postdoctoral Training
Neuropathology Institute, University Hospital of Zürich, Switzerland
Research Interests
The family of transmissible spongiform encephalopathies (TSEs) includes scrapie in sheep; bovine spongiform encephalopathy in cattle; chronic wasting disease (CWD) in deer, elk and moose; and Kuru, Gerstmann-Sträussler-Scheinker and Creutzfeldt-Jakob diseases (CJD) in humans. A once heretical view that is now widely accepted states that exposure to a nucleic acid-free, protease resistant form of the endogenous cellular host prion protein (PrPC), termed PrPSc, solely initiates and propagates species-specific TSEs. Outbreaks of a new, variant form of CJD in Europe have raised serious concern that the species barrier between bovine and human TSEs has been breached occurred. Whether CWD or other TSEs can breach or have breached species barriers remains a point of intense investigation.
My main area of interest lies in prion immunology. This includes deciphering the cellular and molecular mechanisms of prion accumulation and replication in lymphoid organs, with the ultimate goal of developing therapeutic strategies to ablate subsequent neuroinvasion and disease transmission. My lab is extending current work investigating the role of Complement in peripheral prion pathogenesis of mouse scrapie by developing mouse models suitable for studying Chronic Wasting Disease. We are elucidating the molecular mechanisms of prion accumulation and replication in mouse scrapie using established murine models.
We are also exploring new prion detection and diagnostic techniques, including in vitro prion amplification using protein misfolding cyclic amplification (PMCA). We are using PMCA to investigate potential prion reservoirs in the environment, including water, soil and feces. We are also characterizing prion strains using PMCA in conjunction with other biochemical and biological methods to determine the molecular underpinnings of prion species barriers and strain adaptation.
A third area of interest lies in prion disease therapeutics. We are currently developing a novel siRNA delivery system that efficiently and specifically targets neurons, suppresses PrPc expression and ultimately cures prion diseases in vitro and in vivo.
Current Staff
Bruce Pulford, PhD, Senior Research Associate
Ted Johnson, Research Associate
Heather Bender, Research Associate
Crystal Meyerret, Graduate Research Associate
Brady Michel, Graduate Research Associate
Christy Wyckoff, Graduate Research Associate
Brea Smith, Graduate Research Associate
Ginny Forster, Undergraduate Research Associate
Look for the Zabel Lab on
Selected Manuscripts
Pub Med for Zabel MD.
T.A. Nichols, Bruce Pulford, Christy Wyckoff, Crystal Meyerett, Brady Michel, Kevin Gertig, Jean E. Jewell, Glenn C. Telling and M.D. Zabel (2009) Detection Of Protease-Resistant Prion Protein In Water From A CWD-Endemic Area Prion. Accepted.
Nicholas J. Haley, Candace Mathiason, Mark D. Zabel , Glenn C. Telling, and Edward A. Hoover (2009) Detection of PrPRES and CWD prions in conventional test-negative deer exposed to urine and feces from CWD-positive deer. Journal of General Virology. Submitted
Nicholas J. Haley, Mark D. Zabel , Glenn C. Telling, and Edward A. Hoover (2009) Detection of CWD Prions in Urine and Saliva of Deer by Transgenic Mouse Bioassay PLoS One 4(3):e4848. In Press
Alexander Mildner, Hauke Schmidt, Wolfgang Brück, Matthias Mack, Marija Djukic, Mark D. Zabel, Josef Priller & Marco Prinz (2009) CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain. In Press.
Timothy D. Kurt, Glenn C. Telling, Mark D. Zabel, and Edward A. Hoover (2009) Trans-species amplification of CWD prions by serial PMCA . Virology. In Press
Meyerett C, Michel B, Pulford BP, Spraker TR, Nichols TA, Johnson T, Kurt TD, Hoover EA and Zabel MD (2008) In vitro strain adaptation of CWD prions by serial protein misfolding cyclic amplification. Virology 382(2):267-76
Mark Zabel, Christina Greenwood, Alana M. Thackray, Bruce Pulford, Willem Rens and Raymond Bujdoso (2008) Perturbation of mature lymphocyte populations by insertional mutation of a prion protein transgene. Immunology 127(2):226-36
Jouvin-Marche E, Attuil-Audenis V, Aude-Garcia C, Rachidi W, Zabel M, Podevin-Dimster V, Siret C, Huber C, Martinic M, Riondel J, Villiers CL, Favier A, Naquet P, Cesbron JY, Marche PN. (2006) Overexpression of Cellular Prion
Protein Induces an Antioxidant Environment Altering T Cell Development in the Thymus. Journal of Immunology 176(60):3490-97.
Kurt,TD, Perrott MR, Wilusz CJ, Wilusz J, Supattapone S, Telling GC, Zabel MD and Hoover EA (2007) Efficient in vitro amplification of chronic wasting disease. PrPres Journal of Virology 81 (17): 9605-9608
Zabel MD, Heikenwalder M, Prinz M, Arrighi I, Schwarz P, von Teichman AF, Kranich J, Haas KM, Zeller N, Heikenwalder M, Tedder TF, Weis JH, Aguzzi A. (2007) Stromal Complement Receptor CD21/35 Facilitates Lymphoid Prion Colonization and Pathogenesis. Journal of Immunology 179:6144-6152