Thursday, December 26, 2024
12/26/2024
Summary Formation of vascular lumen of appropriate size, or tubulogenesis, is one of critical steps during vascular development. Many vascular diseases including venous malformations (VM) are associated with malformed or enlarged lumens. However, we still have a limited understanding of molecular events that regulate vascular lumen size. Parent R01 award titled “Role of SHE and ABL signaling in vascular tubulogenesis” explores the roles of SH2 domain protein E (SHE) and Abelson kinase (ABL) signaling during vascular tube formation in the zebrafish model and human cell culture. It also tests the role of these pathways in VM cell culture model, and in xenografting VM cells into a mouse. However, there is no live animal model for VM that has been previously generated, which prevented us from testing the tole of SHE and ABL signaling in live animals. The proposed diversity extension focuses on two proposed aims: 1) Develop zebrafish model for human venous malformation (VM); 2) Test the role of SHE and ABL signaling in the zebrafish VM model. The proposed research for the diversity candidate is a logical extension of the parent R01 award and will fill this gap. The research proposal will include generation of transgenic zebrafish line, which expresses mutated Tie2 protein, previously identified in human VMs. We will subsequently utilize the generated line to investigate the role of SHE protein and ABL signaling in VM pathogenesis. The proposed experiments will establish live animal (zebrafish) model for human venous malformations and will test the role of SHE and ABL signaling in this model. The proposed strategy will help to understand the pathology of human VMs and contribute to the development of new therapeutic strategies for VMs. This award will also enable training of the candidate, which comes from an underrepresented background. Training activities will include formal mentoring, an ethics in research course, participating in research conferences, manuscript and grant application writing and others. The appointment will help to foster diversity in science. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).