Evaluation of the functions of RhoA and RhoC GTPases in actin polymerization of myeloid cells

• Grant number: 25/09050-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Mariana Lazarini
• Grantee: Sofia Santos Mosna
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Acute Myeloid Leukemia (AML) is a hematological malignancy characterized by a blockage in the differentiation of immature hematopoietic cells, leading to the accumulation of myeloid blasts in the bone marrow and impairment of normal hematopoiesis. Despite significant advances in treatments over recent years, therapeutic limitations persist across patient subgroups, highlighting the need for greater understanding of the basic mechanisms underlying AML. Rho GTPases are key regulators of cytoskeletal dynamics and are involved in various cellular processes essential for hematopoiesis. Our research group has previously demonstrated that RhoA and RhoC proteins play important roles in the morphology, proliferation, migration, and adhesion of myeloid cells. In the present study, we aim to evaluate the impact of RhoA and RhoC knockdowns on actin polymerization in myeloid cells, as well as their potential association with FMNL1 signaling pathway, a known regulator of this process. We will perform fractionation assays to separate soluble and polymerized actin pools, in addition to GST pull-down and western blot analyses. Our findings will contribute to a better understanding of the RhoA and RhoC mediated signaling pathways in cytoskeletal rearrangement in myeloid cells, which underlies multiple cellular functions implicated in leukemogenesis. (AU)