Krupa Patel
Pronouns: she/her/hers
Research Mentor(s): Karl Desch
Research Mentor School/College/Department: Pediatrics / Medicine
Program:
Authors: Krupa Patel, Christopher Bidlack, Karl Desch
Session: Session 5: 2:40 pm – 3:30 pm
Poster: 100
Abstract
Blood coagulation is a critical process in closed circulatory systems, to prevent life threatening hemorrhage after damage to blood vessels. When it does not function correctly, the coagulation system can become overactive, leading to pathologic thrombosis formation in the deep veins, and/or embolisation into the circulation of the lung, a potentially life threatening situation. Multiple environmental and genetic factors influence an individual’s risk for abnormal thrombosis. This study aims to analyze a plasma protein known to play a critical role in the regulation of normal blood clotting, Antithrombin (AT). Currently, there is no functional high throughput method to test the impact of missense mutations in AT. This project aims to create a cDNA encoding a fusion protein allowing for the display of AT on the surface of a cell so that variant antithrombin can be tested for function while still associated with the DNA that encodes it. Our lab had success creating a cDNA fusion protein that encoded for SERPINC1 (the gene which encodes for AT) and successfully expressed on the surface of a cell. However, we were unable to verify that the AT function against thrombin or factor Xa remained intact. This study hopes to build off this model and to find alternative transmembrane AT fusion proteins that allow for a functional AT displayed on the cell surface. The cDNA code will then be confirmed using DNA sequencing and will then be used for transfection into mammalian tissue culture cells. When employed in a mutagenesis screen, this AT fusion protein will help to address the current lack of understanding on the functional effects of all possible missense variants of the SERPINC1. Future research will use the results of this study, if successful, to create and build a database of the functional impacts of all possible mutations in SERPINC1. This database will help physicians/care-takers better understand their patients risk of thrombosis due to mutations in SERPINC1.
