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, 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, which revealed that African American and Hispanic patients have a higher risk of developing neutralizing anti-FVIII antibodies. Current projects include basic science investigations of FVIII expression in endothelial cells; further investigations of FVIII immunogenicity and hemophilic immune responses; development of novel resuscitation fluids containing engineered red blood cells and platelets; development of algorithms to predict bleeding risk for patients receiving ECMO therapy; and analysis of blood samples from long-COVID subjects to evaluate potential indicators of immunothrombosis risk.

ACTIVE GRANTS

1. Health Resources and Services Administration (Machin, U. of Pittsburgh)
Title: The “INHIBIT” Hemophilia Registry
Role: PI on scientific subaward
1.20 calendar
Direct + Indirect costs: $1.077M
Project period: 7/1/2024-6/30/2029

The major goal of this project is to conduct a natural history study of prospectively enrolled hemophilia A patients before their first exposures to therapeutic factor VIII (FVIII). Blood samples will be analyzed to investigate the naive immune response to FVIII.

2. DoD Multi-Domain Operations grant funding mechanism
Title: Development of an Off the Shelf Erythrocyte-Based Resuscitation Fluid for Hemostasis and Improved Oxygen Delivery
Role: MPI (corresponding), with Dr. Mark Osborn Univ of Minnesota)
1.20 calendar
Direct + Indirect costs: $2.0M
Project period: 03/06/23-03/25/27

The major goal of this project is to engineer red blood cells and platelets to render them less immunogenic, and to utilize platelets as efficient clotting factor delivery vehicles, so these cells can be combined with plasma or other fluids for trauma resuscitation.

3. DoD Multi-Domain Operations grant funding mechanism
Title: Development of Predictive Algorithms for Patient Bleeding or Clotting During Extracorporeal Membrane Oxygen Support
Role: PI
1.20 calendar
Direct + Indirect costs: $3.855M
Project period: 10/01/2024-09/30/28

The major goal of this project is to develop algorithms to predict the risk of serious bleeding while on extracorporeal membrane oxygen support (ECMO) therapy. We will utilize bioinformatics methods to analyze clinical data and serial blood samples collected from subjects receiving ECMO.

More Research Interests:

Hemophilic immune responses to therapeutic factor VIII
Blood coagulation Factor VIII – basic science
COVID-19 and long-COVID – blood profiling to identify correlates with clinical outcomes
Novel resuscitation fluids as alternatives to whole blood transfusion
Coagulopathies associated with ECMO (extracorporeal membrane oxygenation)

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.