Laia Caja Puigsubira research group

Oxidative and Metabolic stress in cancer

If you are interested in current openings in our laboratory, you are welcome to send an email including your CV to Laia Caja Puigsubira

Our lab focuses on two devastating cancer types, glioblastoma, and hepatocellular carcinoma. Glioblastoma (GBM) is the most common malignant brain tumor in adults. There is no cure, and patients undergoing modern treatment approaches (surgical resection, radiotherapy, and chemotherapy) have a median survival of only 15 months. Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, its prognosis depends on the tumor stage, when diagnosed at an early-stage, the 5-year survival rate is 70%; however, if diagnosed at an advanced-stage and treated with systemic therapies, the median survival is only ~1 year.

Oxidative stress in GBM

Tumors, including GBM, present particularly high levels of oxidative stress, generally caused by an increase in reactive oxygen species (ROS) production or a decrease in intracellular ROS-scavengers, the balance between the production and protective systems is known as the intracellular redox state. It is known that ROS in synchrony with cellular metabolism regulate the maintenance of stem cells. My research group focuses on understanding the mechanisms of action of NADPH oxidases and the role of other ROS modulators in GSC biology and how they impact GBM microenvironment. We have previously shown that NADPH oxidase 4, which produces superoxide, promotes self-renewal in GBM (García‐Gómez, P. et al 2022).

Elucidating how reactive oxygen species are regulated in GBM will enable us to identify novel redox-based therapeutic targets for developing complementary treatment options.

Metabolic stress adaptation in GBM and HCC

This project aims to identify new metabolic therapeutic targets. We aim at exploiting adaptation mechanisms to nutrient starvation activated by cancer cells regardless of their origin or mutational burden by focusing on two cancer types: HCC and GBM. Moreover, we want to understand how adaptation to lack of nutrients impacts the cellular response to Transforming growth factor β (TGFβ1), a pathway coupled to the progression of both tumor types. Elucidating how tumor cells adapt to limited nutrients will enable us to identify novel metabolic-based therapeutic targets for developing complementary treatment options in combination with targeting growth factor pathways affected by metabolic adaptation. For example, lack of Glutamine impacts HCC cells proliferation, clonogenicity, and stemness. Not only that, but lack of Glutamine impacts TGFβ signaling activation limiting its capacity to induce epithelial to mesenchymal transition (EMT), as we have published in this preprint 2024