Ongoing research is organized around three main lines:
1- Cellular protection mechanisms activated by endoplasmic reticulum stress in astrocytes during inflammatory processes.
During inflammatory processes, the accumulation of misfolded proteins in the endoplasmic reticulum activates the unfolded protein response (UPR), a mechanism that restores cellular homeostasis and, when unsuccessful, can trigger apoptotic pathways. Our group identified and characterized a mechanism of Ca2+ release from the endoplasmic reticulum that activates the protective phase of the UPR in astrocytes through a calcineurin- and PERK-dependent signaling pathway, associated with protective responses in models of inflammation and cerebral ischemia.
2- The role of endoplasmic reticulum stress activation in cell death mechanisms in a model of neurodegenerative gangliosidosis (Tay–Sachs and Sandhoff diseases).
3- Long-term goal: to develop a therapeutic strategy for patients with GLUT-1 deficiency (GLUT1-DS), based on the evaluation of a compound that increases mitochondrial Ca2+ levels in astrocytes, enhances ATP production, and significantly reduces neuroinflammation.
Figure 1: Global calcium increases following the addition of a high concentration of the stress inducer tunicamycin.
Figure 2: Cytoprotective role of Ca2+–calcineurin and PERK in acute brain injury.
COMPETITIVE RESEARCH FUNDS
Ongoing
- NIH AG058778-01A1, Agreement Nos. 165148/165147, UTHSCSA-IMMF. Principal Investigator in Argentina: Mariana Bollo. “Regulation of ER stress–activated UPR kinase PERK in neurodegenerative disease.”
- FONCyT–PICT I-A (#2019-00155).“Study of calcineurin-mediated modulation of PERK during the acute phase of endoplasmic reticulum stress.”
Selected Completed Grants
- FONCyT–PICT (#2017-0618).“Calcium-dependent regulation of the acute phase of endoplasmic reticulum stress.”
- NIH R21 #NS085732, Agreement, UTHSCSA-IMyMF. “Regulation of the unfolded protein response after acute brain injury.”
PUBLICATIONS (LATEST FIVE YEARS)
Morales C, Fernandez M, Ferrer R, Raimunda D, Carrer DC, Bollo M. Ursodeoxycholic Acid Binds PERK and Ameliorates Neurite Atrophy in a Cellular Model of GM2 Gangliosidosis. (2023) International Journal of Molecular Sciences.; 24(8):7209. ISSN: 2076-6327.
Feliziani C., Fernandez, M, Quasollo G., Holstein D., Bairo, M., Paton J.C., Paton A.W., de Batista J., Lechleiter J.D. and Bollo M. Ca2+ signalling system initiated by Endoplasmic reticulum stress stimulates PERK activation. (2022) Cell Calcium 106: 102622, ISSN: 0143-4160.
Morales C., Bisbal M. and Bollo M. Molecular modulation by lentivirus-delivered specific shRNAs in endoplasmic reticulum stressed neurons. (2021) J Vis Exp, ISSN: 1940-087X. (170). doi: 10.3791/61974.
Cabrera Zapata L.E., Bollo M and Cambiasso MJ. Estradiol-mediated axogenesis of hypothalamic Neurons requires ERK1/2 and Ryanodine Receptor dependent intracelular Ca2+ rise in male rats. (2019) Front Cell Neurosci 13:122. ISSN- 1662-5102.
Virgolini MJ, Feliziani C, Cambiasso MJ, Lopez PHH and Bollo M. Neurite atrophy and apoptosis mediated by PERK signaling after accumulation of GM2-ganglioside. (2019) Biochim Biophys Acta Mol Cell Res. 1866(2): 225-239. Editorial: Elseiver, Amsterdam, Holanda ISSN-0167-4889.
- Etzler J.&, Bollo M. &, Holstein D& Deng J.J., Perez V., Lin D., Richardson A.G. and Lechleiter J.D. Cyclophilin D Over-Expression Increases Mitochondrial Complex III Activity and Accelerates Supercomplex Formation. (2017) Arch Biochem Biophys 613: 61-68. Editorial: Elseiver, Amsterdam, Holanda ISSN:0003-9861
- Complete and updated list available here.
TEAM
2024
