Neurosciences
Cell Signaling and Apoptosis
Joan Comella
Researchers
Joaquín López Soriano, Bruna Barneda Zahonero, Nuria Llecha Cano, Laura Planells Ferrer, Jorge Urresti Ibáñez
Researchers in training
Koen Galenkamp, Elena Coccia, Blanca Sanuy Escribano
SUMMARY
We have characterized the role of two death receptor antagonists in nervous system physiology. On one hand, we have studied the role of Lifeguard (LFG) in the etiology and development of neuroblastoma. We have observed LFG is downregulated in the most aggressive and undifferentiated tumors, and there is a clear correlation between LFG levels and neuroblastoma differentiation. In addition, LFG expression is directly repressed by MYCN, whose overexpression is linked with increased neuroblastoma metastatic properties.
In addition, we have characterized the role of FAIM-L in Alzheimer disease patients’ neurons and in animal models. FAIM-L levels are dowregulated both in AD patients and mice. In addition, the protection afforded by TNF as a pro-inflammatory signal against amyloid beta toxicity is lost when FAIM-L levels decrease. Overall, our results support the idea that FAIM-L levels can contribute to determine the effects of TNF in neurons in a neuroinflammatory context such as Alzheimer disease, thus pointing at FAIM-L as a likely future target for the disease.
PUBLICATIONS
- Carriba P, Comella JX.
Amyloid Beta, TNFα and FAIM-L; Approaching New Therapeutic Strategies for AD.
Front Neurol. 2014, 5:276. eCollection 2014.
PMID: 25566181 - Cornago M, Garcia-Alberich C, Blasco N, Vall-Llaura N, Nager M, Herreros J, Comella JX, Sanchis D, Llovera M.
Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe.
Cell Death Dis. 2014, 5:e1435
PMID: 25275596 - Planells-Ferrer L, Urresti J, Soriano A, Reix S, Murphy DM, Ferreres JC, Borras F, Gallego S, Stallings RL, Moubarak RS, Segura MF, Comella JX.
MYCN repression of Lifegurad/FAIM2 enhances neuroblastoma aggressiveness.
Cell Death Dis. 2014, 5:e1401
PMID: 25188511 - Moreno M, Negrotto L, Río J, Moubarak R, Martín I, Bustamante MF, Comella JX, Vidal-Jordana A, Pérez-Boza J, Montalban X, Comabella M.
Activation-induced cell death in T lymphocytes from multiple sclerosis patients.
J. Neuroimmunol. 2014, 272(1-2):51-55
PMID: 24793898
MAIN RESEARCH PROJECTS
View- PROJECT TITLE: Cell Signalling and Apoptosis
FINANCING ENTITY: CIBERNED (CB06/05/1104).
DURATION: 2014 (year renewal) AMOUNT: 43.634,70 €
PRINCIPAL INVESTIGATOR: Joan X. Comella - PROJECT TITLE: Senyalització Cel•lular i Apoptosis
FINANCING ENTITY: Generalitat de Catalunya – Direcció General de Recerca – Convocatòria de Suport al Grups de Recerca (SGR2009-346).
DURATION FROM: 2009 TO: 2014. AMOUNT: 45.760 €
PRINCIPAL INVESTIGATOR: Joan X. Comella - PROJECT TITLE: Relevancia fisiológica y patológica de los antagonistas de los receptores de muerte (FAIM, Lifeguard y FLIP) en el sistema nervioso.
FINANCING ENTITY: Dirección General de Investigación – Ministerio de Ciencia e Innovación (SAF2010_19953).
DURATION FROM: 2011 TO: 2014. AMOUNT: 400.000 €
PRINCIPAL INVESTIGATOR: Joan X. Comella - PROJECT TITLE: Propiedades emergentes de la relación neurona-glia en la enfermedad de Alzheimer.
FINANCING ENTITY: CIBERNED (Proyectos Cooperativos) (2013/01)
DURATION FROM: 2013 TO: 2015. AMOUNT: 350.000 € (70.000 € for VHIR subproject)
PRINCIPAL INVESTIGATOR: Ignacio Torres Alemán (Instituto Cajal, Madrid) - PROJECT TITLE: Neuroinflamación, TNF y antagonistas de los receptores de muerte (FAIM-L): relevancia en neurodegeneración.
FINANCING ENTITY: Dirección General de Investigación Científica y Técnica – Ministerio de Economía y Competitividad (SAF2013-47989-R).
DURATION FROM: 2014 TO: 2016. AMOUNT: 240.000 €
PRINCIPAL INVESTIGATOR: Joan X. Comella