Kathleen P. Pratt

Ph.D.

Department of Primary Appointment:
School of Medicine
Medicine
Title
Professor and Vice Chair for Research
Location: Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Hematologic and immune disorders
Immune tolerance
Office Phone

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

2014 - present Associate Professor, F. Edward Hébert School of Medicine, Department of Medicine, Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD

2013-2014 Assistant 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

2007 - present: Research awards (grants) from Bayer, CSL Behring, Pfizer, Grifols, Inc.

2008 “Henri Chaigneau” Prize of the Association Française des Hémophiles

2019 Dean's Impact Award, F. Edward Hébert School of Medicine, Department of Medicine, Uniformed Services University of the Health Sciences

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

Spiegel PC, Jr., Jacquemin M, Saint-Remy J-MR, Stoddard BL, Pratt KP. 2001. Structure of a factor VIII C2-domain - Immunoglobulin G4k Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII. Blood98: 13-19. Plenary paper. PMID: 11418455

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

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

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. PubMed PMID: 27471234

Ettinger RA, Liberman JA, Gunasekera D, Puranik K, James EA, Thompson AR, Pratt KP. FVIII proteins with a modified immunodominant T-cell epitope exhibit reduced immunogenicity and normal FVIII activity. Blood Advances 2018: 2(4), 309-322. PubMed PMID: 29444

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 2018: 58(5), 1171-81. PMID: 29464723

Lacroix-Desmazes S, Voorberg J, Lilicrap D, Scott DW, Pratt KP. Tolerating Factor VIII: Recent Progress. Frontiers in Immunology 2020 Jan 10;10:2991. doi: 10.3389/fimmu.2019.02991. PMID: 31998296.

Karim AF, Soltis AR, Sukumar G, Konigs C, Ewing N, Dalgard CL, Wilkerson MD, Pratt KP. Hemophilia A inhibitor subjects show unique PBMC gene expression profiles that include up- regulated immune modulators. Frontiers in Immunology 2020, June 12. Doi: 10.3389/fimmu.2020.01219. PMCID: PMC7303277