PRINCIPAL INVESTIGATOR

POSTDOCTORAL RESEARCH COLLABORATORS:

• José Miguel Brito Armas (CIBERNED Researcher)
• Judith Noda Mayor (FIISC Investigator)

PHD STUDENTS AND TRAINEES:

• Alessandro Marrero Gagliardi (PhD student ACIISI, 2018-2021)

RESEARCH LINES:

The research lines in this laboratory focus on the genetic pathways involved in neurodegenerative disorders, particularly Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). We are developing mouse models that will allow us to study the molecular mechanisms underlying these diseases, particularly looking at TDP-43, a key protein in the pathophysiology of both ALS and FTD. We are building worldwide collaborations with experts in genetics, biochemistry and cell biology interested in our research studies.

FUNDED PROJECTS:

• Neuronal function of TDP-43 and the potential role of USP10 in its regulation (PI17/00244 – “Investigando la función neuronal de TDP-43 y el posible papel de USP10 en su regulación”). PI: Abraham Acevedo. Institute of Health Carlos III (2018-2020, 146,712.50 €).

• Screening of chemical libraries from The Canary Islands for natural and synthetic compounds with bio-pharmacological effects against neurodegenerative disorders (ProID2017010167 – “Identificación de compuestos naturales y sintéticos presentes en las quimiotecas Canarias con potencial biofarmacológico contra enfermedades neurodegenerativas”). PIs: Abraham Acevedo and Félix Machín. The Canary Islands Agency of Research, Innovation and Information Sciences (2018-2020, 70,000 €).
• Incorporation of new groups into the CIBERNED consortium (CB18/05/0000). PI: Abraham Acevedo Arozena. Institute of Health Carlos III, ISCIII (2019-2020, 70,000 €).
• Role of TDP-43, the key protein in ALS and FTD on the stress response (PIFUN13/18). PI: Abraham Acevedo Arozena. Canary Islands Foundation of Health Research, FUNCANIS (2019-2020, 21,900 €).

PUBLICATIONS 2019:

• Rodriguez-Rodriguez AE, Donate-Correa J, Rovira J, Cuesto G, Luis-Ravelo D, Fernandes MX, Acevedo-Arozena A, Diekmann F, Acebes A, Torres A, Porrini E. Inhibition of the mTOR pathway: A new mechanism of β cell toxicity induced by Tacrolimus. Am J Transplant. 2019 Dec;19(12):3240-3249. doi: 10.1111/ajt.15483
• Stewart M,Lau P,Banks G,Bains RS,Castroflorio E,Oliver PL,Dixon CL, KruerMC,Kullmann DM,Acevedo-Arozena A,Wells SE,Corrochano S,Nolan PM. Loss of Frrs1 disrupts synaptic AMPA receptor function, and results in neurodevelopmental, motor, cognitive and electrographical abnormalities. DisModel Mech. 2019 Feb 22;12(2). doi: 10.1242/dmm.036806
• Tan S,Kermasson L,Hoslin A,Jaako P,Faille A,Acevedo-Arozena A,Lengline E, Ranta D,Poirée M,Fenneteau O, Ducou le Pointe H,Fumagalli S,Beaupain B, Nitschké P,Bôle-Feysot C,de Villartay JP,Bellanné-Chantelot C,Donadieu J, Kannengiesser C,Warren AJ, Revy P. EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome. 2019 Jul 18;134(3):277-290. doi: 10.1182/blood.2018893404
• Nair RR,Corrochano S,Gasco S,Tibbit C,Thompson D,Maduro C,Ali Z,Fratta P,Arozena AA,Cunningham TJ,Fisher EMC. Uses for humanised mouse models in precision medicine for neurodegenerative disease. Mamm Genome. 2019 Aug;30(7-8):173-191. doi: 10.1007/s00335-019-09807-2
• De Giorgio F, Maduro C, Fisher EMC, Acevedo-Arozena A. Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis. Dis Model Mech. 2019 Jan 2;12(1). pii: dmm037424. doi: 10.1242/dmm.037424

OTHER SELECTED PUBLICATIONS FROM THE LAST 10 YEARS:

• Fratta P, Sivakumar P, Humphrey J, Lo K, Ricketts T, Oliveira H, Brito-Armas JM, Kalmar B, Ule A, Yu Y, Birsa N, Bodo C, Collins T, Conicella AE, Mejia Maza A, Marrero-Gagliardi A, Stewart M, Mianne J, Corrochano S, Emmett W, Codner G, Groves M, Fukumura R, Gondo Y, Lythgoe M, Pauws E, Peskett E, Stanier P, Teboul L, Hallegger M, Calvo A, Chiò A, Isaacs AM, Fawzi NL, Wang E, Housman DE, Baralle F, Greensmith L, Buratti E, Plagnol V, Fisher EM, Acevedo-Arozena A. Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis. EMBO Journal. 2018 Jun 1;37(11). doi: 10.15252/embj.201798684
• Corrochano S, Blanco G, Williams D, Wettstein J, Simon M, Kumar S, Moir L, Agnew T, Stewart M, Landman A, Kotiadis VN, Duchen MR, Wackerhage H, Rubinsztein DC, Brown SDM, Acevedo-Arozena A. A genetic modifier suggests that endurance exercise exacerbates Huntington’s disease. Human Molecular Genetics. 2018 May 15;27(10):1723-1731. doi: 10.1093/hmg/ddy077
• Joyce PI, Fratta P, Landman AS, McGoldrick P, Wackerhage H, Groves M, Busam BS, Galino J, Corrochano S, Beskina OA, Esapa C, Ryder E, Carter S, Stewart M, Codner G, Hilton H, Teboul L, Tucker J, Lionikas A, Estabel J, Ramirez-Solis R, White JK, Brandner S, Plagnol, V, Bennet DL, Abramov AY, Greensmith L, Fisher EM, Acevedo-Arozena A. Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration. Hum Mol Genet. 2016 Jan 15;25(2):291-307. doi: 10.1093/hmg/ddv471
• Joyce PI, McGoldrick P, Saccon RA, Weber W, Fratta P, West SJ, Zhu N, Carter S, Phatak V, Stewart M, Simon M, Kumar S, Heise I, Bros-Facer V, Dick J, Corrochano S, Stanford MJ, Luong TV, Nolan PM, Meyer T, Brandner S, Bennett DL, Ozdinler PH, Greensmith L, Fisher EM, Acevedo-Arozena A. A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity. Hum Mol Genet. 2015 Apr 1;24(7):1883-97. doi: 10.1093/hmg/ddu605
• Corrochano S, Mannikko R, Joyce PI, McGoldrick P, Wettstein J, Lassi G, Raja Rayan DL, Blanco G, Quinn C, Liavas A, Lionikas A, Amior N, Dick J, Healy EG, Stewart M, Carter S, Hutchinson M, Bentley L, Fratta P, Cortese A, Cox R, Brown SDM, Tucci V, Wackerhage H, Amato AA, Greensmith L, Koltzenburg M, Hanna MG, Acevedo-Arozena A. Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis. Brain. 2014 Dec;137(Pt 12):3171-85. doi: 10.1093/brain/awu292