07/17/2019
NIH Grant to Study Mechanism of Blood Clotting Factor Secretion Renewed
The National Heart, Lung, and Blood Institute, part of the National Institute of Health, has awarded Bin Zhang, PhD, Genomic Medicine Institute, a four-year, $1.6 million grant renewal to continue his study of a protein transport receptor (LMAN1-MCFD2 complex) required for the secretion of blood clotting factor V (FV) and factor VIII (FVIII). The initial grant was awarded in 2008.
Dysregulation of FV and FVIII contributes to various bleeding disorders, including venous thrombosis and hemophilia. Dr. Zhang and his team previously discovered that a rare bleeding disorder called F5F8D is characterized by the severe downregulation of both FV and FVIII levels, which is caused by genetic mutations that affect the LMAN1 and MCFD2 proteins. Under normal conditions, LMAN1 and MCFD2 form a protein complex that interacts with both FV and FVIII, which suggests the proteins may play an important role in transporting the coagulation factors throughout the cell and aid in their effective secretion.
With this additional funding, the team aims to understand the mechanism of the LMAN1-MCFD2 complex as it relates to LMAN1- and MCFD2-mediated transportation and secretion of FV and FVIII. They will investigate how the complex binds and releases the proteins and explore the LMAN1-MCFD2 secretory pathway as a therapeutic target for bleeding and thrombotic diseases.
