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. These included determination of high-resolution crystal structures that elucidated the mechanism of fibrin polymerization and the orientation of coagulation factor VIII (FVIII) on activated platelet surfaces. She has studied the structure, function and immunogenicity of blood 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. Among these, we recently characterized CD4 T-cell responses to FVIII epitopes in subjects with severe hemophilia A due to an intron-22 inversion mutation (Gunasekera et al., Frontiers in Immunology, in press). We are collaborating with Dr. Margaret Ragni (U. of Pittsburgh) on a natural history study of neutralizing anti-FVIII antibodies in hemophilia A that will include analysis of samples collected during the initial development of these deleterious anti-drug antibody responses. Results will also be relevant to studies of other unwanted anti-drug antibody responses.

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, in collaboration with USU investigators Dr. Mark Haigney, COL David Saunders and their groups.

Another recently funded project addresses a fundamental need in trauma resuscitation: patients who experience substantial blood loss require transfusions with blood from appropriately matched donors to avoid transfusion reactions (e.g. to ABO and Rh antigens on red blood cells and other blood components). Plasma, platelets and/or packed red blood cells are also needed. In collaboration wth Dr. Mark Osborn (U of Minnesota) we will develop "off-the-shelf" resuscitation fluids as potential alternatives to blood from live donors. Techniques will include engineering of red blood cells and platelets grown in cell culture and testing of alternatives to plasma as a carrier solution. These alternative components and solutions will be compared to whole blood, plasma, etc. using functional assays. Dr. Steve Dumler's group (USU) are local collaborators on this interesting project.