Kathleen Pratt Ph.D.

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

Dr. Pratt’s laboratory employs a multidisciplinary approach to studies at the interface between blood coagulation, inflammation and immunology. Early work consisted of molecular modeling and x-ray crystallographic studies, including high-resolution crystal structures that elucidated the mechanism of fibrin polymerization. She has studied the structure, function and immunogenicity of blood coagulation factor VIII (FVIII) for over 20 years. Her studies of alloimmune responses to FVIII encompass structure/function studies, investigations of cellular immune responses to FVIII, mapping of T-cell and B-cell epitopes using multiple techniques, RNASeq/transcriptomics and TCR repertoire analysis of PBMCs and specific lymphocyte populations, and characterization of T-cell clones and polyclonal lines from patients as well as hemophilic mice. Recent work has included analysis of the national “My Life Our Future” database for hemophilia A and a natural history study analyzing antibody responses in ~400 hemophilia A patients. Results revealed that African American and Hispanic patients have a higher risk of developing neutralizing anti-FVIII antibodies, and ongoing wet-lab studies are revealing mechanisms contributing to this risk. In collaboration with Dr. David Scott (USU), we are developing a hemophilia A mouse model transgenic for a FVIII-specific B-cell receptor, which will be used as an in vivo model to study FVIII-specific immune responses and various tolerogenic strategies.

In 2020, our laboratory pivoted in response to the COVID-19 pandemic. Current studies include profiling of plasma, serum and cellular fractions from hospitalized COVID-19 patients, focusing particularly on biomarkers and mechanisms of immunothrombosis. Additional collaborative studies of “long-covid” patient samples will launch in 2023.

Career Highlights: Positions, Projects, Deployements, Awards and Additional Publications

2019 Professor and 2020 Vice Chair for Research, F. Edward Hébert School of Medicine, Department of Medicine, Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD

2014 - 2019 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

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

2021 National Hemophilia Foundation "Hemophilia Researcher of the Year" award

Representative 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

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

Pratt KP, Gunasekera D, Vir P, Tan S, Pierce GF, Olsen C, Butenas S, Mann KG. Neutralizing and non-neutralizing antibodies in Black and White hemophilia A subjects: A natural history profile. Blood Advances, in press.