David W. Scott, Ph.D.

David W. Scott, Ph.D.

David Scott

Name: David W. Scott, Ph.D.

Department of Primary Appointment: Dept. of Medicine
Position: USU Faculty
Title: Professor and Vice Chair for Research

Affiliated Departments: Emerging Infectious Diseases,

Email: david.scott@usuhs.edu (link sends e-mail)
Office Phone: (301) 295-3618
Fax Number: (301) 295-3618
Room: A3069

Profile

  • M.S. University of Chicago
  • Ph.D. Yale
  • Post-doctoral training: Oxford University, England

Research: Induction of tolerance for adverse immune responses in autoimmunity and hemophilia

David Scott Lab

The breakdown of self-tolerance in autoimmunity, as well the response to biotherapeutics for monogenic diseases, results in serious morbidity and potential mortality for millions of Americans.   Understanding and applying the induction of immunologic tolerance to prevent and/or reverse these adverse immune responses is the primary focus of the Scott lab.  This includes utilizing gene therapy with transduced B cells, as well as the design of engineered T regulatory cells for tolerance.  The main systems involve the modulation of autoimmune diseases, like multiple sclerosis and type 1 diabetes, as well as prevention and reversal of inhibitory antibody formation in hemophilia. The basis of our approach has been the use of chimeric proteins comprised of an immunoglobulin (Ig) heavy chain and the target domains or peptides, and delivery into B cells as tolerogenic antigen-presenting cells.  This has led recently to the discovery of putative regulatory epitopes in IgG that could serve to turn on regulatory T cells, and strong preliminary data in multiple disease models.  Further work utilizes tolerogenic nanoparticles that have shown efficacy in several disease models.  Our lab continues to be actively involved in the mechanisms by which T regulatory cells can modulate both innate and adaptive immune responses, and the creation of novel engineered human antigen-specific CAR Tregs and CD8 cells.

Selected Publications

Zambidis E, Scott, DW. Epitope-specific tolerance induction with an engineered immunoglobulin. 1996. Proc Nat Acad Sci 93: 5019. PMID: 8643522

Agarwal RK, Kang Y, Zambidis E, Scott, DW, Chan C, Caspi R,R. 2000. Retroviral gene transfer of an immunoglobulin-antigen fusion protein protects from autoimmune disease. J Clin Invest 106:245. PMID: 10903340

Melo M, Qian J, El-Amine M, Agarwal R, Soukhareva N, Kang Y, Scott, DW. 2002. Gene transfer of immunoglobulin-fusion proteins into B cells prevents and treats autoimmune diseases. J Imm 168:4788. PMID: 11971030.

Lei T-C, Scott, DW. 2005.Induction of tolerance to fVIII inhibitors by gene therapy with immunodominant A2 and C2 domains presented by B-cells as Ig fusion proteins. Blood 105:4865. PMID: 15769892.

De Groot, AS, Moise, L, McMurry, JA, Wambre, E, Van Overtvelt, L, Moingeon, P, Scott, DW, and Martin W.  2008. Activation of natural regulatory T cells by IgG Fc–derived peptide “Tregitopes.” Blood. 112:3303-11. PMID: 18660382.

Skupsky, J, Zhang, AH, Su, Y, and Scott, DW. 2010. B-cell Delivered Gene Therapy Induces     Functional T Regulatory Cells and Leads to a Loss of Antigen-Specific Effector Cells. Molecular Therapy, 18:1527-35. PMID: 20485267.

Zhang AH, Skupsky J, Scott DW. 2011. Effect of B-cell depletion using anti-CD20 therapy on inhibitor formation and immune tolerance induction to human factor VIII in hemophilia A mice.  Blood, 117: 223-226.  PMID: 21160036.

Su, Y, Zhang, AH, Noben, N, and Scott, DW. 2011. B-cell gene therapy for tolerance induction: host but not donor B cell derived IL-10 is necessary for tolerance. Frontiers in Microbial Immunology, 2:154.  PMID: 21811487.

Matheu, MP, Su, Y, Greenberg, ML, Blanc, C, Parker, I, Scott, DW, Cahalan, MD 2012. TLR4-activated B cells out-compete TLR9-activated B cells to establish peripheral tolerance, PNAS Plus, 109:E1258-66. doi: 10.1073/pnas.1205150109.

Scott DW, Pratt KP, and Miao CH. 2013. Progress Towards Inducing Immunologic Tolerance to Factor VIII.  Blood (Invited peer-reviewed) 121 : 4449-4456.

Maldonado RA, LaMothe RA, Ferrari JD, Zhang AH, Rossi RJ, Griset AP, O’Neil C, Alreuter DH, Johnston L, Farokhzad OC, Langer R, Scott DW, von Andrian UH, Kishimoto TK. 2015. Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance. PNAS, 112(2):E156-65. PMID: 25548186

Kim YC, Zhang AH, Su Y, Rieder SA, Rossi RJ, Ettinger RA, Pratt KP, Shevach EM and Scott DW. 2015.  Engineered antigen-specific human regulatory T cells:  Immunosuppression of FVIII-specific T- and B-cell responses, Blood 125: 1107. PMID: 25498909.

Gupta N, Culina S, Meslier Y, Dimitrov J, Arnoult C, Delignat S, Gangadharan B, Lecerf M, Justesen S, Gouilleux-Gruart V, Salomon BL, Scott DW, Kaveri SV, Mallone R, Lacroix-Desmazes S. 2015.  Regulation of immune responses to protein therapeutics by transplacental induction of T cell tolerance. Sci Transl Med. 2015 Feb 18;7(275):275ra21. PMID: 25696000