Investigation of metabolic vulnerabilities in myelodysplastic syndrome for the development of new therapeutic strategies

• Grant number: 25/03052-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fabíola Traina
• Grantee: Manuela Albuquerque de Melo
• Supervisor: Jan Jacob Schuringa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University Medical Center Groningen (UMCG), Netherlands
• Associated to the scholarship: 23/09514-9 - Investigation of mitochondrial metabolism in the biology of myelodysplastic syndrome, BP.DR

Abstract

Myelodysplastic syndrome (MDS) is a heterogeneous group of hematological malignancies characterized by ineffective hematopoiesis, cytopenias and risk of progression to acute myeloid leukemia, which mainly affects the elderly population. Mitochondrial dysfunction and stem cell exhaustion are two features of aging commonly found in MDS. Clonal hematopoiesis is perpetuated by inflammation and is involved in the development and progression of MDS. Recently, it has been identified that metformin suppresses clonal hematopoiesis. However, the contribution of mitochondrial metabolism to pathophysiology, cell survival and management of patients with MDS has yet to be investigated. The aims of this study are to investigate mitochondrial metabolism vulnerabilities and to identify potential novel treatment strategies for patients with MDS. In this way, we will (i) conduct multi-omics analysis for drug targeting screening from exome and transcriptome MDS data, (ii) evaluate mitochondrial respiration and mitochondrial metabolism in primary MDS hematopoietic cells using Seahorse XF96 and Citek AuroraTM Spectral flow cytometry system, respectively, and (iii) investigate the effect of respiratory chain complex inhibitors on the mitochondrial capacity and cell survival in primary MDS hematopoietic cells. Bioinformatics analyzes for the omics data and statistical analyzes will be performed as appropriate. (AU)