SALVADOR MARTÍNEZ PÉREZ & RUT VALDOR ALONSO
Salvador Martínez Pérez
Professor with tenure, PhD, MD
Rut Valdor Alonso
Assistant professor, PhD
Universidad Miguel Hernandez, Elche/Universidad de Murcia, IMIB-Arrixaca
Role of autophagy in the immune function of perivascular cell populations in brain that present stem cell properties and inflammatory function that might be modulated for cell therapy in pathologies assocciated to neurodegeneration and in Glioblastoma Multiforme progression. Our first goal is understand the molecular mechanisms implicated in the evasion of the perivascular immune response during interaction and perivascular infiltration of the tumor cells in the Glioblastoma Multiforme (GBM), and therefore, to determine what types of autophagy and their functions might be implicated.
Autophagy is known for its various regulatory roles in immune cells (Figure on autophagy functions in innate and adaptive immune cells). The ability of autophagy to degrade regulation intermediaries in immune cells and the increasingly frequent use of autophagy inhibitors in clinical trials makes it a possible candidate to modulate the immune response of perivascular stem cells of brain that are implicated in several neurodegeneration pathologies and assist the Glioblastoma Multiforme progression (GBM).
Our group is mainly studying how autophagy affects the immune function of brain perivascular cells and its implication in the vascular changes and perivascular infiltration of tumor cells during GBM (Figure on Autophagy regulation in perivascular cells during GBM). Our objectives are based on the hypothesis that Macroautophagy (MA), as a bulk degradation process in perivascular immune cells, might be implicated in the energetic metabolism and remodelling required for the interaction with the tumor cells, whereas Chaperone Mediated Autophagy (CMA), as a high selective process in its degradation of proteins, consequently could be important in the reprogramming of immune phenotype (through proteome changes) induced upon interaction with GBM cells.
For our studies on autophagy, our recent formed group caters with the international collaboration of labs of expertise in ´´Autophagy in the tumor biology and immune system´´, such as Dr. Cuervo and Macian labs in Albert Einstein College of Medicine, New York, and with the essential tools (autophagy reporters, lentiviral vectors expressing shRNAs for different autophagy proteins, LAMP-2A deficient mice…) to characterize those processes that will be available to us to further achieve the goals of our study.