Redox State and Chemoresistance: Metabolic Characterization of TNBC Cells Using Time-Resolved Flow Cytometry

• Grant number: 25/08167-9
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: August 22, 2025
• End date: December 21, 2025
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Claudiana Lameu
• Grantee: Fernanda Wagner Caldora
• Supervisor: Jessica Perea Houston
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: New Mexico State University (NMSU), United States
• Associated to the scholarship: 23/09047-1 - Chemoresistance in triple negative breast cancer: the relation with P2X7 and P2Y2 purinergic receptors, BP.IC

Abstract

Triple negative breast cancer (TNBC) corresponds to approximately 15% of breast cancer cases and remains the most challenging subtype to treat, due to its marked aggressiveness, high recurrence rate, and pronounced resistance to chemoterapy. To survive and proliferate within the tumor microenvironment, tumor cells often present an altered metabolism, known as metabolic reprogramming. The metabolic pathways are intrinsically coupled with the biosynthesis and redox cycle of NADH and its phosphorylated analogue NADPH. While NADH primarily functions as an electron donor in the mitochondrial respiratory chain, sustaining oxidative phosphorylation and ATP production, NADPH provides reducing power for anabolic biosynthesis and antioxidant defense systems. Together, these cofactors are central to maintaining cellular energy production, macromolecular synthesis and redox homeostasis.The main objective of this research internship abroad is to assess the fluorescence lifetime of NAD(P)H in paclitaxel resistant TNBC cells compared to parental cells, as these lifetimes reflect different coenzyme binding states and the balance between glycolysis and oxidative phosphorylation. In collaboration with Professor Jessica Houston, we aim to characterize the metabolic profile of TNBC cells with intrinsic and acquired chemoresistance to paclitaxel. Furthermore, we will investigate how pharmacological inhibition of the purinergic receptors P2X7 and P2Y2 affects NAD(P)H fluorescence dynamics, to determine the role of these receptors to the metabolic phenotype associated with chemoresistance. (AU)