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, together with Drs. Anwar Ahmed and Sara Contente at USU, of the national “My Life Our Future” database for hemophilia A (HA), which is the largest database in the world containing clinical and demographic data from individuals with HA. Initial results confirmed earlier work from our lab and others indicating that African American and Hispanic patients have a higher risk of developing neutralizing anti-FVIII antibodies, a serious clinical disorder (PMID 36696179). Subsequent studies employing whole genome sequence analysis and cutting-edge bioinformatics has identified risk factors for this immune disorder including specific combinations of HLA alleles (PMID 41644240) and variants in additional coding and concoding genes (submitted).   Our complementary wet-lab studies studies are revealing mechanisms contributing to this risk, by characterizing human T-cell and B-cell responses to factor VIII (e.g., PMID 36459, 39233012, 41391568, ). Results of these studies are relevant to studies of antigen-specific immune responses and of other unwanted anti-drug antibody responses.

In 2020, our laboratory pivoted in response to the COVID-19 pandemic. Current studies include a collaboration with Drs. Mark Haigney and Davis Saunders (USU) nclude profiling of plasma, serum and cellular fractions from hospitalizto analyze serial plasma samples collected from Long-COVID patients. 

Other recently funded projects address 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 are working to 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. 

Other military-relevant projects include a major effort to comprehensively analyze blood and plasma samples from patients receiving extracorporeal membrane oxygenation (ECMO); a primary goal is to identify biomarkers for excessive bleeding and/or thrombosis adn develop predictive algorithms that could guide anticoagulation and other clinical decisions in close to real time. Finally,  we are now launching a collaboration with Prof Regina Day (USU) to study a potential therapeutic to restor platelet function after radiation exposure, and another collaboration with COL Patrick Walker to evaluate platelet and plasma markers and dysregulation in a pig model of ECMO resuscitation devices and protocols.