Hematology Lab- Pratt
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.