Autophagy in neuroinflammation and oncohematological diseases
We are evaluating the impact of the autophagic pathway activation on: pro-inflammatory mediators production, activation, migration and survival of macrophages and leukemic cells. Under neuroinflammatory conditions, such as Alzheimer’s disease (AD), Parkinson disease and endotoxemia, the presence of pro-inflammatory cytokines in the central nervous system (CNS) has been detected. Several studies showed that glial cells and peripheral leukocytes respond to innate receptor (TLRs) ligands, to Abeta42 or alpha-synuclein, releasing cytokines. Our group demonstrated that TLR agonists, such as LPS, CpG ODN and PGN can increase mFPR2 microglial expression, which is a chemoattractant receptor associated to AD. Moreover, we observed that rapamycin and trehalose (autophagy inductors), can modulate the inflammatory response of alpha-synuclein-activated microglial cells. We also demonstrated that TLR2 can induce autophagy in both murine macrophages and human leukemic B cells.
We are focused on: 1) to dissect alpha-synuclein endocytosis and autophagy induction in macrophages; 2) to evaluate the impact of alpha-synuclein stimulation on lysosomal and mitochondrial functions and viability in macrophages; 3) to study the effects the autophagic response on activation and survival in leukemic leukocytes.
In the period 2001-2005, he did his postdoctoral work at the National Institutes of Health, USA. Since 1995 he has been a member of the CONICET Research Career, where he is currently a Principal Researcher at CIBICI.
In addition, he teaches in the Department of Clinical Biochemistry FCQ-UNC, occupying the position of Associate Professor by Competition (Lic) and Acting Professor in the subject Clinical Chemistry II, and Director of the Specialisation in Clinical Biochemistry – Haematology Area at FCQ-UNC.
She was Head of the Oncohematology Laboratory at the Instituto Oncológico Universitario – Hospital Nacional de Clínicas – UNC, and Co-director of a CONICET Assistant Research Fellowship (until 2021) and a CONICET Postdoctoral Fellowship (until 2022).
In addition, she teaches in the Department of Clinical Biochemistry FCQ-UNC, holding the position of Assistant Professor by competition in the subject Clinical Chemistry II.
She is a CONICET Doctoral Fellow, under the direction of Dr. Pablo Iribarren. She is doing her PhD in Chemical Sciences at the FCQ-UNC, and her thesis deals with the topic: «Study of the response of microglial cells and peripheral leukocytes in neuroinflammation and its relationship with autophagy».
She is also a lecturer in the Department of Clinical Biochemistry FCQ-UNC, holding the position of Assistant Professor in the subject Clinical Chemistry II.
Collaborators and Partners
Collaborators and Partners
Dr. Nicholas Ktistakis (Babraham Institute, Cambridge, UK)
Selected Publications
Iribarren P., Chen K., Hu J., Gong W., Cho E.H., Lockett S., Uranchimeg B. and Wang J.M. CpG-containing oligodeoxynucleotide promotes microglial cell up-take of amyloid 1-42 peptide by up-regulating the expression of the G-protein coupled receptor mFPR2. FASEB J. 19:2032-4. 2005. doi: 10.1096/fj.05-4578fje.
Iribarren P., Chen K, Hu J, Zhang X, Gong W, Wang JM. IL-4 inhibits the expression of mouse formyl peptide receptor 2, a receptor for amyloid beta1-42, in TNF-alpha-activated microglia. J Immunol. 175:6100-6. 2005. doi: 10.4049/jimmunol.175.9.6100.
Arroyo DS, Soria JA, Gaviglio EA, Garcia-Keller C, Cancela LM, Rodriguez-Galan MC, Wang JM, Iribarren P. Toll-like receptor 2 ligands promote microglial cell death by inducing autophagy. FASEB J. 27:299-312. 2013. doi: 10.1096/fj.12-214312.
Bussi C, Peralta Ramos JM, Gaviglio EA, Arroyo DS, Gallea JI, Wang JM, Celej MS and Iribarren P. Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death. Sci Rep. 7:43153. 2017. doi: 10.1038/srep43153.
Peralta Ramos JM, Bussi C, Gaviglio EA, Arroyo DS, Baez NS, Rodriguez-Galan MC, Iribarren P. Type I IFNs Are Required to Promote Central Nervous System Immune Surveillance through the Recruitment of Inflammatory Monocytes upon Systemic Inflammation. Front Immunol. 8:1666. 2017. doi: 10.3389/fimmu.2017.01666.
Bussi C, Peralta Ramos JM, Arroyo DS, Gallea JI, Ronchi P, Kolovou A, Wang JM, Florey O, Celej MS, Schwab Y, Ktistakis NT, Iribarren P. Alpha-synuclein fibrils recruit TBK1 and OPTN to lysosomal damage sites and induce autophagy in microglial cells. J Cell Sci. 131(23). 2018. pii: jcs226241. doi: 10.1242/jcs.226241. Publicación de Tapa de la revista (COVER).
Arroyo DS, Gaviglio EA, Peralta Ramos JM, Bussi C, Avalos MP, Cancela LM, Iribarren P. Phosphatidyl-Inositol-3 Kinase Inhibitors Regulate Peptidoglycan-Induced Myeloid Leukocyte Recruitment, Inflammation, and Neurotoxicity in Mouse Brain. Front Immunol. 2018 Apr 17;9:770. doi: 10.3389/fimmu.2018.00770.
Rodriguez CM, Bussi C, Arroyo DS, Sastre D, Heller V, Stanganelli C, Slavutsky I, Iribarren P. Effects of rapamycin in combination with fludarabine on primary chronic lymphocytic leukemia cells. Leuk Lymphoma. 2019 May;60(5):1299-1303. doi: 10.1080/10428194.2018.1529309.
Arroyo DS, Rodriguez CM, Bussi C, Manzone-Rodriguez C, Sastre D, Heller V, Stanganelli C, Slavutsky I, Iribarren P. Increased expression of Autophagy protein LC3 in two patients with progressing chronic lymphocytic leukemia. Front Endocrinol. 2020 Jul 22;11:321. Doi: 10.3389/fendo.2020.00321.
Gaviglio EA, Peralta Ramos JM, Arroyo DS, Bussi C, Rodriguez-Galan MC*, Iribarren P*. Systemic sterile induced-co-expression of IL-12 and IL-18 drive IFN-γ-dependent activation of microglia and recruitment of MHC-II-expressing inflammatory monocytes into the brain. Int Immunopharmacol. 2022 Jan 21;105:108546. doi: 10.1016/j.intimp.2022.108546. * Autoría Compartida.