Kathleen Pratt, Ph.D.

Kathleen P. Pratt, Ph.D.

Name: Kathleen P. Pratt, Ph.D.

USU Department of Primary Appointment: 
Medicine
Title: 
PhD
Faculty Rank: 
Associate Professor
Location: 
Uniformed Services University of the Health Sciences, Bethesda, MD

Research Interests:
Protein immunogenicity
Immune tolerance

Office Phone: 
(301) 295-3607

Education

1976 BA Liberal Arts, The Evergreen State College, Olympia, WA
1984 BS Mathematical Sciences, University of Washington, Seattle, WA
1992 PhD Biophysical Chemistry, Cornell University, Ithaca, NY

Biography

Kathleen Pratt received her PhD in Biophysical Chemistry from Cornell University, in the laboratory of Harold A. Scheraga. As a postdoctoral fellow and staff scientist she determined crystal structures of blood coagulation proteins, including the C2 domain of factor VIII (FVIII), which binds to activated platelet surfaces. Her laboratory has utilized mutagenesis plus surface plasmon resonance to comprehensively map the B-cell epitopes on this important region of the FVIII protein. Over the past decade, they have also mapped immunodominant T-cell epitopes in FVIII and characterized human CD4 T-cell responses using blood samples from hemophilia A patients who develop neutralizing anti-drug antibodies to therapeutically administered FVIII. Her laboratory is currently pursuing studies of protein immunogenicity, immune tolerance, protein engineering, and novel approaches to avoid or reverse the effects of clinically important anti-drug antibodies.

Representative publications, projects, and/or deployments

  • 2013 - present Associate Professor, F. Edward Hébert School of Medicine, Department of Medicine, Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD
  • 2008-2013 Assistant Research Professor, University of Washington School of Medicine, Division of Hematology, Seattle, WA
  • 2006-2013 Assistant Member, Puget Sound Blood Center Research Institute, Seattle, WA
  • 2003-2006 Research Scientist, Puget Sound Blood Center, Seattle, WA
  • 1999-2003 Staff Scientist, Hutchinson Cancer Research Center, Seattle, WA

Bibliography

  • Pratt KP, Shen BW, Takeshima K, Davie EW, Fujikawa K, Stoddard BL. 1999. Structure of the C2 domain of human factor VIII at 1.5 angstrom resolution. Nature 402: 439-42. PMID: 10586887
  • James EA, Kwok WW, Thompson AR, Pratt KP. 2007.Analysis of CD4 T-cell responses to FVIII in a mild hemophilia A patient indicates early loss of tolerance to a C2 domain self peptide and sustained loss of tolerance to the wild-type peptide J Thromb Haemostas5:2399-47. PMID: 18034765
  • Ettinger RA, James EA, Kwok WW, Thompson AR, Pratt KP. 2009. Lineages of human T-cell clones, including TH17/TH1 cells, isolated at different stages of anti-factor VIII immune responses. Blood 114: 1423-8. PMID: 19549986
  • James EA , van Haren SD, Ettinger RA, Fjnvandraat K, Liberman J, Kwok WW, Voorberg J, Pratt KP. 2010. T-cell responses in two unrelated hemophilia A inhibitor subjects include an epitope at the factor VIII R593C missense site. J Thromb Haemostas 9:689-99. PMID: 21251204
  • Lewis KB, Hughes RJ, Epstein MS, Josephson NC, Kempton CL, Kessler CM, Key NS, Howard TE, Kruse-Jarres R, Lusher JM, Walsh CE, Watts RG, Ettinger RA, Pratt KP. 2013. Phenotypes of allo- and autoimmune antibody responses to FVIII characterized by surface plasmon resonance. PLOS One 8(5): e61120. PMID: 23667433
  • Nguyen P-CT, Lewis KB, Ettinger RA, Schuman JT, Lin JC, Healey JF, Meeks SL, Lollar P, Pratt KP. 2014. High resolution mapping of epitopes on the C2 domain of factor VIII, using surface plasmon resonance. Blood 123(17): 2732-9.PMID: 24591205
  • Gunasekera D, Ettinger RA, Liu M-C, Hughes RJ, Epstein MS, Cole SC, Barrett JC, Thompson AA, Withycombe J, Pratt KP. 2015. Factor VIII gene variants and inhibitor risk in hemophilia A patients. Blood 126(7): 895-904. PMID: 25617427
  • Pratt KP. 2016. Engineering less immunogenic and antigenic factor VIIII proteins. Cellular Immunol. 301:12-17. PMID: 26566286
  • Ettinger EA, Paz P, James EA, Gunasekera D, Aswad F, Thompson AR, Matthews DC, Pratt KP. T cells from three hemophilia A subjects recognized the same HLA-restricted FVIII epitope with a narrow TCR repertoire. Blood 2016: 128(16):2043-2054. PMID: 27471234
  • Gunasekera D, Zimring JC, Pratt KP. A unique MHCII-binding register correlates with HLA-DR11-associated immunogenicity of the major K blood group antigen. Transfusion, in press.