Projects

Project 1: The Structural Basis for Immune Recognition of Factor VIII

Project Leader: Dr. Pete Lollar

Location: Emory University

Objectives

  • Develop X-ray crystallographic structures of fVIII and fVIII immune complexes.
  • Characterize fVIII antibody epitopes and fVIII immune complexes by HDX MS, EM and SPR spectroscopy.
  • Characterize fVIII immune complexes by analytical ultracentrifugation.

Project 2: The Immunobiology of Factor VIII

Project Leader: Dr. Sean Stowell

Location: Emory University

Objectives

  • Define the role of fVIII glycans on inhibitor formation.
  • Define the role of anti-fVIII antibodies on fVIII immune complex formation and inhibitor development.
  • Define the impact of microbiota on anti-αGal antibody development and subsequent inhibitor formation.

Project 3: Immunopharmacology of FVIII Bioengineering and Gene Therapy

Project Leader: Dr. Christopher Doering

Location: Emory University

Objectives

  • Analyze the molecular composition and immune reactivity of bioengineered recombinant infusion products as well as liver-directed AAV and HSC-directed LV gene therapy derived fVIII.
  • Identify critical design parameters associated with immunogenicity and inhibitor eradication potential of liver-directed AAV-fVIII gene therapy.
  • Evaluate the immunogenicity and inhibitor eradicating potential of non-genotoxic HSC-directed LV gene therapy protocols.

Skills Development Core Directors: Dr. Shannon Meeks and Dr. Trent Spencer

Administrative Core Director: Dr. Shannon Meeks