42000-Markusic, David
Faculty

David M. Markusic, PhD

Assistant Research Professor of Pediatrics

Address
Herman B Wells Center for Pediatric Research
1044 W Walnut Street, R4-155

Indianapolis, IN 46202

Bio

I have over ten years of research experience optimizing liver gene delivery in murine and canine disease models using different viral vector systems. I have successfully obtained competitive funding from the NIH, Bayer Hemophilia Awards Program, and Pfizer Aspire Hemophilia Awards to work on optimizing adeno-associated virus liver gene delivery in murine and canine hemophilia B animal disease models, to elucidate the mechanism of tolerance induction with pre-existing immunity, to model and minimize detrimental anti-vector immune responses, to define minimally effective vector doses, and to assess the risks of administering suboptimal vector doses. My research work has made vital contributions to advancing liver directed AAV gene therapy as a novel approach for reversing pre-existing antibody responses in enzyme replacement therapies. I have had my work published in the leading journals of hemophilia and gene therapy and have consistently published manuscripts from my multi-year funded studies. 

Key Publications

Palaschak B, Marsic D, Herzog RW, Zolotukhin S, Markusic DM. An Immune-Competent Murine Model to Study Elimination of AAV-Transduced Hepatocytes by Capsid-Specific CD8+T Cells. Mol Ther Methods Clin Dev. 2017 Jun 16;5:142-152. PubMed PMID: 28480313; PubMed Central PMCID: PMC5415329.

Markusic DM, Hoffman BE, Perrin GQ, Nayak S, Wang X, LoDuca PA, High KA, Herzog RW. Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies. EMBO Mol Med. 2013 Nov;5(11):1698-709. PubMed PMID: 24106230; PubMed Central PMCID: PMC3840486.

Martino AT, Basner-Tschakarjan E, Markusic DM, Finn JD, Hinderer C, Zhou S, Ostrov DA, Srivastava A, Ertl HC, Terhorst C, High KA, Mingozzi F, Herzog RW. Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8+ T cells. Blood. 2013 Mar 21;121(12):2224-33. PubMed PMID: 23325831; PubMed Central PMCID: PMC3606062.

Martino AT, Suzuki M, Markusic DM, Zolotukhin I, Ryals RC, Moghimi B, Ertl HC, Muruve DA, Lee B, Herzog RW. The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9-dependent innate immune responses in the liver. Blood. 2011 Jun 16;117(24):6459-68. PubMed PMID: 21474674; PubMed Central PMCID: PMC3123017.

 

Titles & Appointments

  • Assistant Research Professor of Pediatrics
  • Education
    2007 PhD University of Amsterdam
    2002 MSC University of Amsterdam
    1994 BS University of California, San Diego
  • Research

    My current research interests include AAV immune tolerance induction (ITI) therapy for hemophilia A, the more common form of hemophilia, to develop AAV-ITI based therapies to treat autoimmune disease and food allergy, to delve into the mechanism of AAV-ITI, and to develop improved mouse models to study and prevent capsid-specific CD8 T cell elimination of AAV transduced hepatocytes.

  • Professional Organizations
    American Association of Immunologists
    American Society of Gene and Cell Therapy
    American Society of Hematology
  • Awards
    Org: NIH NHBLI
    Desc: Ruth Kirschstein National Research Service Award Postdoctoral Fellowship
    Scope: National
    Date:
    Org: University of Florida
    Desc: Henry A. Kokomoor Award for Excellence in Pediatrics Research
    Scope: Department
    Date:

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