CV Team leader

Alicia Mansilla BIOSKETCH

Since I initiated my research career I was interested in the study of the nervous system. During my PhD I worked from a molecular perspective, working at the levels of transcription, splicing and translation. My PhD project at the laboratory of Flora de Pablo at CIB/CSIC focused on the insulin gene. I discovered novel regulatory mechanisms of this gene, based on variations in transcript structure. These mechanisms are important for normal nervous system development. As a further step in the field of gene expression regulation, I moved to David Rubinsztein’s laboratory In Cambridge UK. His lab is a world reference in protein degradation as related to neurodegenerative diseases. There, I contributed to the understanding of Parkinson`s disease pathology, studying the protein LRRK2 and how it impairs proteasome substrate clearance.  In addition, I studied the deleterious consequences of autophagy inhibition over proteasome activity, a work that was a key conceptual advance to the field (377 citations). Upon returning to Spain, I joined the lab of Alberto Ferrús at the Cajal Institute, where I have continued studying protein degradation mechanism in neurological diseases.  In 2016 I joined IRYCIS (Hospital Ramon y Cajal) with a JIN project aimed to develop the use of trehalose for the treatment of neurodegenerative diseases and the following year I received funding from the Community of Madrid for the recruitment of a predoctoral fellow for the development of this project. During the last years I have been involved in a project that emerged from my stay at the Cajal Institute, regarding the neural calcium sensor NCS1 and its mechanisms to regulate synaptogenesis. In this context, I lead a collaborative project with the groups of Dr.Maria Jose Sánchez Barrena and Prof. Ana Martínez at CSIC, aimed to test novel drugs that modulate NCS-1 activity.  In September 2019 I started my contract as Ramón y Cajal fellow at the University of Alcalá in the physiology unit of the Systems Biology Department within the group of Prof. Pedro de la Villa. Thanks to the agreement between UAH and IRYCIS I will continue to carry out my research work in the same laboratory, with the benefit at all levels of the double membership: a university and a biomedical institute. 

PUBLICATIONS:

  • Canal Martín, A.; et al. (corresponding author) 2019. Insights into real-time chemical processes in a calcium sensor protein-directed dynamic library. Nature communications. 10-1, pp.2798.
  • Campillo, N; et al.  2018. Deciphering the inhibition of the neuronal calcium sensor 1 and the guanine exchange factor Ric8a with a small phenothiazine molecule for the rational generation of therapeutic synapse function regulators. Journal of Medicinal Chemistry.  Jul 26;61(14):5910-5921.
  • Mansilla, A.; et al.  2018. Molecular Mechanisms that change Synapse Number. Journal of Neurogenetics. Sep;32(3):155-170
  • . Mansilla, A.; et al.  2017. Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome. Feb 7;114(6):E999-E1008.
  • Mansilla, A.; et al. 2016. Ligand independent requirements of steroid receptors EcR and USP for cell survival. Cell death and differentiation. 23-3, pp.405-416.
  • Tenorio, J.; et al. 2014. A new overgrowth syndrome is due to mutations in RNF125 Human mutation. 35-12, pp.1436-1441.
  • Romero-Pozuelo, J.; et al. 2014. The guanine-exchange factor
    Ric8a binds to the ca2+ sensor NCS-1 to regulate synapse number and probability of reléase. Journal of cell Science. 127-19, pp.4246-4259.Gradilla, AC. et al;. 2011. Isoform-specific regulation of a steroid hormone nuclear receptor by an E3 ubiquitinligase in Drosophila melanogaster. Genetics. 189-3, pp.871-883.
  • Lichtenberg, M.; et al. 2011. The Parkinson’s disease protein LRRK2
    impairs proteasome substrate clearance without affecting proteasome catalytic activity. Cell Death & Disease. 2-196.
  • Sahota, VK.; et al. 2009. Troponin I and Tropomyosin regulate chromosomal tability and cell polarity. Journal of Cell Science. 122-15, pp.2623-2631.
  • korolchuk, VI.; et al. Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Molecular Cell. 33-4, pp.517-527.
  • Hernandez-Sanchez, C.; et al. (4/2). 2008. Evolution of the insulin receptor family and receptor isoform expression in vertebrates. Molecular Biology and Evolution. 25-6, pp.1043-1053.
  • Hernández-Sanchez, C.; et al. (5/4). 2006. The regulated expression of chimeric tyrosine hydroxylase-insulin transcripts during early development. Nucleic Acids Research. 34-12, pp.3455-3464.
  • Mansilla, A.; et al. Developmental regulation of a proinsulin messenger RNA generated by intron retention. EMBO Reports. 6-121, pp.1182-1187.
  • Hernández-Sanchez, C.; et al. 2003. Upstream AUGs in embryonic proinsulin mRNA control its low translation level. EMBO Journal. 22-20, pp.5582-5592.
  • Hernandez-Sanchez, C.; et al. 2006. Proinsulin in development: new roles for an ancient prohormone. 49-6, pp.1142-1150.

 Research projects and grants

  • Synapse modulators: small molecules with big impact in nervous system disorders. Caixa Impulse grant from Fundacion Bancaixa. (IRYCIS). 01/07/2018-01/12/2020. 70.000 €. Principal investigator.
  • Developing the use of a disacharide as a treatment for neurodegenerative diseases. JIN programme from MICINN (IRYCIS). 01/12/2016-01/12/2019. 169.100 €. Principal investigator.
  • Neuroprotection through synaptogenesis. MICINN. (Instituto Cajal-CSIC). 2013-2015. Team member.
  • Synapse number and the integration of olfactory stimuli Plan Nacional MICINN. (Instituto Cajal-CSIC). 2010-2012. Team member.
  • Therapeutic approaches for codon reiteration diseases. Wellcome trust grants. (Cambridge Institute for Medical Research.UK). 2007-2012. Team member.
  • Zebrafish models of Parkinson’s and Alzheimer’s disease. Medical Research Council grant. (Cambridge Institute for Medical Research.UK). 2004-2008. Team member.
  • Gene expression regulation, molecular basis and signaling mechanism of proinsulin and related factors in development. Plan Nacional MINECO (CIB-CSIC). 2004-2007. Team member

Patents.

  • Ruth Perez; Andrea Canal; Maria Jose Sánchez-Barrena; Alicia Mansilla. EP19382242.6. 2Acylhydrazones for the treatment of neurological diseases2 02/04/2019. CSIC y Fibio HRyC.
  • 2. Ruth Perez; Andrea Canal; Maria José Sanchez; Alicia Mansilla. P201830933. “Acilhidrazonas para el tratamiento de enfermedades neurológicas”. 27/09/2018. CSIC y Fibio HRyC
  • Ana Martinez; Carmen Gil; Nuria Campillo; Maria José Sánchez-Barrena; Alicia Mansilla;Alberto Ferrus. P201531358. “Aminophenotiazines for synapse number modulation”
    Spain. 23/09/2015.CSIC

Institutional responsibilities.

Member of IRYCIS Research Comission from 2018

Memberships of scientific societies

AMIT Asociación Mujeres Investigadoras y Tecnólogas, from 2017

SENC Sociedad Española de Neurociencia, from 2017