Inmunomoduladores y regeneración de órganos

Laboratorio de inmunomoduladores y regeneración de órganos

Laboratory of Immunomodulators and organ regeneration

INVESTIGADOR RESPONSABLE

Dr. Eduardo Chuluyán

Investigador Principal del CONICET

Información del Laboratorio

Línea de Investigación

Palabras Claves: Inmunología, inflamación, cáncer de páncreas, trasplante de órganos sólidos, medicina regenerativa, organos, plataformas bioartificiales.

El laboratorio de inmunomoduladores y regeneración de órganos, es un laboratorio de investigación básica y traslacional que tiene como objetivo general buscar soluciones a los problemas planteados vinculados al trasplante de órganos y tejidos. En este sentido se trata de buscar herramientas diagnósticas y terapéuticas que limiten el daño por isquemia reperfusión, reduzcan el rechazo del órgano y la fibrosis, y eviten la reactivación de infecciones latentes vinculadas a la inmunosupresión. Por otro lado se busca generar órganos bioartificiales que permitan suplir la gran demanda de órganos y evitar el rechazo de los mismos.

De esta manera, los objetivos específicos propuestos se orientan a:

Identificar los efectos y el mecanismo de acción de inmunomoduladores, en los pacientes trasplantados renales, renopancreáticos y hepáticos.
Buscar y caracterizar biomarcadores del estado de inmunológico de los pacientes trasplantados inmunosuprimidos.
Generar órganos bioartificiales utilizando matrices extracelulares.

Investigation line

The laboratory of immunomodulators and organ regeneration, is a laboratory of basic and translational research that has the general objective to find solutions to problems related to organ and tissue transplantation. In this sense it is seeking diagnostic and therapeutic tools that limit ischemia reperfusion injury, reduce organ rejection and fibrosis, and prevent reactivation of latent infections associated with immunosuppression. On the other hand it seeks to create bioartificial organs that allow meet the high demand for organs and prevent rejection of them.
Thus, the proposed specific objectives are to:

Identify the effects and mechanism of action of immunomodulators in renal, liver and simultaneous renopancreas transplant patients.
Search and characterize biomarkers of immune status of immunosuppressed transplant patients.
Generate bioartificial organs using extracellular matrices.

Convenios y Actividades

Convenios en vigencia(cooperación internacional y/o intercambio académico 2012 a la fecha):

Domingo Casadei. Instituto de Nefrología de Buenos Aires, Nephrology.
Juan Iovanna, Director of the Department of Translational Medicine, Head of the Cell Stress team, Center of Research in Cancerology of Marseille (CRCM), INSERM UMR1068, CNRS UMR 7258, Aix-Marseille University and Institut Paoli-Calmettes.
Alejandro Soto-Gutierrez. Pittsburgh University, Pittsburgh, USA

Actividades de transferencia en vigencia 2012 a la fecha:

Instituto de Nefrología de Buenos Aires, Nephrology.

Tesis Doctorales: 10 (2 desde 2012 a la fecha)

Tesis de Licenciatura: 10, 1 desde 2012 a la fecha.

Tesis de maestría: 2 desde 2012 a la fecha.

Actividad Docente (cargo):

Profesor Adjunto Regular, Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires.

Publicaciones

Inhibition of glucuronidation in pancreatic cancer improves gemcitabine anticancer activity. Fraunhoffer NA, Abuelafia AM, Chanez B, Bigonnet M, Gayet O, Roques J, Chuluyan E, Dusetti N, Iovanna J. Cancer Commun (Lond). 2022 Nov;42(11):1212-1216.
Human Endothelial Cell Seeding in Partially Decellularized Kidneys. Haeublein G, Lombardi G, Caro F, Guerrieri D, Remolins C, Incardona C, Casadei D, Chuluyan E. Biomed Res Int. 2022 Jul 13;2022:9018074.
raft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies. Uva PD, Papadimitriou JC, Drachenberg CB, Toniolo MF, Quevedo A, Dotta AC, Chuluyan E, Casadei DH. Am J Transplant. 2019 Feb;19(2):466-474. doi: 10.1111/ajt.15012.
α-lipoic acid reduces postreperfusion syndrome in human liver transplantation – a pilot study. Casciato P, Ambrosi N, Caro F, Vazquez M, Müllen E, Gadano A, de Santibañes E, de Santibañes M, Zandomeni M, Chahdi M, Lazarte JC, Biagiola DA, Iaquinandi JC, Santofimia-Castaño P, Iovanna J, Incardona C, Chuluyan E. Transpl Int. 2018 Dec;31(12):1357-1368. doi: 10.1111/tri.13314.
Targeting REG3β limits pancreatic ductal adenocarcinoma progression through CTGF downregulation. Fraunhoffer NA, Closa D, Folch-Puy E, Abuelafia AM, Calvo EL, Chuluyan E, Iovanna J. Cancer Lett. 2021 Aug 24;521:64-70.
Squamousness gain defines pancreatic ductal adenocarcinoma hepatic metastases phenotype, and gemcitabine response. Fraunhoffer NA, Abuelafia AM, Teyssedou C, Chuluyan E, Bigonnet M, Palazzo L, Gayet O, Nicolle R, Cros J, Iovanna J, Dusetti N.Eur J Cancer. 2021 Sep;155:42-53.
Secretory Leukocyte Proteinase Inhibitor Protects Acute Kidney Injury Through Immune and Non-Immune Pathways. Guerrieri D, Ambrosi NG, Romeo H, Salaberry J, Toniolo MF, Remolins C, Incardona C, Casadei D, Chuluyan E. Shock. 2021 Dec 1;56(6):1019-1027.
Non-SARS-CoV-2 biomedical research in times of pandemic and post-pandemic. Remolins C, Chuluyan E. Medicina (B Aires). 2020;80(5):596-597. Long-term apoptosis-related protein expression in the diabetic mouse ovary.
Fraunhoffer NA, Meilerman Abuelafia A, Aquino Barrientos M, Cimerman KV, Olmos MF, Chuluyan E, Barrios M.PLoS One. 2018 Sep 7;13(9):e0203268. doi:10.1371/journal.pone.0203268. eCollection 2018
Alpha-1-antitrypsin ameliorates inflammation and neurodegeneration in the diabetic mouse retina.Ortiz G, Lopez ES, Salica JP, Potilinski C, Fernández Acquier M, Chuluyan E, Gallo JE.Exp Eye Res. 2018 Sep;174:29-39. doi:10.1016/j.exer.2018.05.013.
Cementoin-SLPI fusion protein binds to human monocytes and epithelial cells and shows higher biological activity than SLPI.Maffía PC, Guerrieri D, Villalonga X, Caro F, Gómez S, Tateosian N, Bogado BP, Sánchez ML, Ambrosi N, Chuluyan E.Sci Rep. 2018 Mar 28;8(1):5332. doi: 10.1038/s41598-018-23680-0.
Alpha Lipoic Acid: A Therapeutic Strategy that Tend to Limit the Action of Free Radicals in Transplantation.Ambrosi N, Guerrieri D, Caro F, Sanchez F, Haeublein G, Casadei D, Incardona C, Chuluyan E.Int J Mol Sci. 2018 Jan 4;19(1). pii:E102. doi: 10.3390/ijms19010102.
Laparoscopic Biopsies in Pancreas Transplantation. Uva PD, Odorico JS, Giunippero A, Cabrera IC, Gallo A, Leon LR, Minue E, Toniolo F, Gonzalez I, Chuluyan E, Casadei DH.Am J Transplant. 2017 Aug;17(8):2173-2177. doi:10.1111/ajt.14259.
Successfull Simultaneous Pancreas Kidney transplantation in a patient with Congenital Partial Lipodystrophy. Leon L, Uva P, Minue E, Pilotti R, Cabrera I, Giunippero A, Gallo A, Osella F, Toniolo F, Chuluyan E, Casadei D. Nefrologia. 2016 Jul-Aug;36(4):450-1. doi: 10.1016/j.nefro.2016.02.005.
REG3β Plays a Key Role in IL17RA Protumoral Effect-Response. Loncle C, Bonjoch L, Folch-Puy E, Lopez-Millan MB, Lac S, Molejon MI, Chuluyan E, Cordelier P, Dubus P, Lomberk G, Urrutia R, Closa D, Iovanna JL. Cancer Res. 2016 Apr 1;76(7):2051. doi: 10.1158/0008-5472.CAN-15-3355.
α-Lipoic Acid Protects Against Ischemia-Reperfusion Injury in Simultaneous Kidney-Pancreas Transplantation. Ambrosi N, Arrosagaray V, Guerrieri D, Uva PD, Petroni J, Herrera MB, Iovanna JL, León L, Incardona C, Chuluyan HE, Casadei DH. Transplantation. 2016 Apr;100(4):908-15. doi: 10.1097/TP.0000000000000981.
IL17 Functions through the Novel REG3β-JAK2-STAT3 Inflammatory Pathway to Promote the Transition from Chronic Pancreatitis to Pancreatic Cancer. Loncle C, Bonjoch L, Folch-Puy E, Lopez-Millan MB, Lac S, Molejon MI, Chuluyan E, Cordelier P, Dubus P, Lomberk G, Urrutia R, Closa D, Iovanna JL. Cancer Res. 2015 Nov15;75(22):4852-62. doi: 10.1158/0008-5472.CAN-15-0896.
SPARC Controls Melanoma Cell Plasticity through Rac1. Salvatierra E, Alvarez MJ, Leishman CC, Rivas Baquero E, Lutzky VP, Chuluyan HE, Podhajcer OL. PLoS One.2015 Aug 6;10(8):e0134714. doi: 10.1371/journal.pone.0134714.
A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette-Guérin-vaccinated Individuals. Peña D, Rovetta AI, Hernández Del Pino RE, Amiano NO, Pasquinelli V, Pellegrini JM, Tateosian NL, Rolandelli A, Gutierrez M, Musella RM, Palmero DJ, Gherardi MM, Iovanna J, Chuluyan HE, García VE. EBioMedicine. 2015 May 30;2(8):884-90.doi: 10.1016/j.ebiom.2015.05.026.
Transglutaminase binding fusion protein linked to SLPI reduced corneal inflammation and neovascularization. Salica JP, Guerrieri D, Maffia P, Croxatto JO, Chuluyan HE, Gallo JE. BMC Ophthalmol. 2015 Feb 4;15:12. doi:10.1186/1471-2415-15-12.
Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option? Ortiz G, Salica JP, Chuluyan EH, Gallo JE. Biol Res. 2014 Nov 18;47:58. doi:10.1186/0717-6287-47-58. Secretory Leukocyte Protease Inhibitor (SLPI) expression downregulates E-cadherin, induces β-catenin re-localisation and triggers apoptosis-related events in breast cancer cells. Rosso M, Lapyckyj L, Amiano N, Besso MJ, Sánchez M, Chuluyan E, Vazquez-Levin MH. Biol Cell. 2014 Sep;106(9):308-22. doi:10.1111/boc.201300075.
The impact of IFN-γ receptor on SLPI expression in active tuberculosis: association with disease severity. Tateosian NL, Pasquinelli V, Hernández Del Pino RE, Ambrosi N, Guerrieri D, Pedraza-Sánchez S, Santucci N, D’Attilio L, Pellegrini J, Araujo-Solis MA, Musella RM, Palmero DJ, Hernandez-Pando R, Garcia VE, Chuluyan HE. Am J Pathol. 2014 May;184(5):1268-73. doi:10.1016/j.ajpath.2014.01.006.
Gene expression profile in delay graft function: inflammatory markers are associated with recipient and donor risk factors. Guerrieri D, Re L, Petroni J, Ambrosi N, Pilotti RE, Chuluyan HE, Casadei D, Incardona C. Mediators Inflamm. 2014;2014:167361. doi: 10.1155/2014/167361.
Anti-tumor effect of SLPI on mammary but not colon tumor growth. Amiano NO, Costa MJ, Reiteri RM, Payés C, Guerrieri D, Tateosian NL, Sánchez ML, Maffia PC, Diament M, Karas R, Orqueda A, Rizzo M, Alaniz L, Mazzolini G, Klein S, Sallenave JM, Chuluyan HE. J Cell Physiol. 2013 Feb;228(2):469-75. doi:10.1002/jcp.24153.
IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease. Jurado JO, Pasquinelli V, Alvarez IB, Peña D, Rovetta AI, Tateosian NL, Romeo HE, Musella RM, Palmero D, Chuluyán HE, García VE. J Leukoc Biol. 2012 Jun;91(6):991-1002. doi: 10.1189/jlb.1211619.
Local and systemic cellular immunity in early renal artery atherosclerosis. Kotliar C, Juncos L, Inserra F, de Cavanagh EM, Chuluyan E, Aquino JB, Hita A, Navari C, Sánchez R. Clin J Am Soc Nephrol. 2012 Feb;7(2):224-30. doi:10.2215/CJN.06270611.
Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model. Cicora F, Roberti J, Vasquez D, Guerrieri D, Lausada N, Cicora P, Palti G, Chuluyan E, Gonzalez P, Stringa P, Raimondi C. Clin Exp Immunol. 2012 Jan;167(1):169-77. doi: 10.1111/j.1365-2249.2011.04487.x.

LIBROS

Chuluyan E, Domingo Casadei. Compendio en inmunopatología en Trasplante renal. I. El rechazo humoral. ISBN: 978-987-45859-1-2. Editorial: Content Medicine. Buenos Aires, Argentina, Junio 2016.
Chuluyan E, Domingo Casadei. Compendio en inmunopatología en Trasplante renal. II. Las infecciones en los trasplantes renales. Editorial: Content Medicine. Buenos Aires, Argentina, Junio 2017.