CIQUIBIC-CONICET-UNC


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Integrantes

DEGANO, Alicia

Investigadora Adjunta de CONICET / Profesora Adjunta UNC
Teléfono: +54 351 5353855 x 3418
E-mail: adegano@fcq.unc.edu.ar

Tema de Investigación

Bases biológicas de desórdenes del neurodesarrollo

El síndrome de Rett (RTT) es una enfermedad del neurodesarrollo que forma parte del grupo de desórdenes asociados a autismo (ASD). Esta patología afecta el SNC durante el desarrollo postnatal, con síntomas que involucran retraso mental, problemas motores, convulsiones y rasgos de autismo. En 1999 se describió que la principal causal de RTT consiste en mutaciones en la proteína unidora de metil-CpG 2 (MeCP2), que actúa como factor de transcripción. Niveles alterados de Mecp2 también han sido detectados en otros ASDs, de manera que establecer el papel de esta proteína durante el neurodesarrollo podría ayudar a establecer el mecanismo patogénico común a estos desórdenes. A tal fin, se crearon modelos animales que carecen de esta proteína o expresan una forma mutada, los cuales reproducen varios de los aspectos de la patología humana. Nuestro objetivo general es definir mecanismos moleculares por los cuales la falta de MeCP2 genera alteraciones en la conectividad neural durante el desarrollo. Como hipótesis de trabajo proponemos que la falta de MeCP2 alteraría la expresión de moléculas involucradas en el establecimiento y mantenimiento de la conectividad nerviosa, participando en los procesos de maduración neuronal, guiado axonal, formación y mantención de sinapsis y plasticidad sináptica dependiente de actividad. Así, utilizamos modelos animales deficientes en Mecp2, cultivos de neuronas, paradigmas de actividad in vivo e in vitro, técnicas biológicas y moleculares con el fin de caracterizar el efecto inducido por la ausencia de Mecp2 sobre la formación y maduración del circuito hipocampal, identificar cascadas de señalización afectadas en ausencia de Mecp2 y establecer relaciones causales entre las alteraciones estructurales en hipocampo y alteraciones cognitivas presentes en ratones mutantes para Mecp2.

Becarios

Publicaciones Seleccionadas

  • Degano, A.L., Park, M.J., Penati J., Lin, Q. and Ronnett G.V. MeCP2 is required for activity-dependent refinement of olfactory circuits. Mol. Cell. Neurosci. 59: 63-75 (2014).
  • Park MJ, Aja S, Li Q, Degano AL, Penati J, Zhuo J, Roe CR, Ronnett GV. Anaplerotic Triheptanoin Diet Enhances Mitochondrial Substrate Use to Remodel the Metabolome and Improve Lifespan, Motor Function, and Sociability in MeCP2-Null Mice. PLoS One. 2014 Oct 9;9(10):e109527.
  • Palmer, A.M.*, Degano, A.L.*, Park M.J., Ramamurty S. and Ronnettt G.V. Normal Mitral Cell Dendritic Development in the Setting of Mecp2 Mutation. Neuroscience 202: 108-116 (2012).
  • Degano, A.L.*, Pasterkamp R.J. and Ronnett G.V. MeCP2 deficiency disrupts axonal guidance, fasciculation, and targeting by altering Semaphorin 3F function. Mol. Cell. Neurosci., 42: 242-255 (2009)
  • Degano, A.L. and Roth, G.A. Synapsin induce proliferation of T-cell lines against myelin basic protein obtained from rats with Experimental Autoimmune Encephalomyelitis. Autoimmunity, 42 (8): 661-666 (2009).

(Ver mas publicaciones-CONICET)

Colaboraciones

  • Dr Gabriele Ronnett, Center for Metabolism and Obesity Research (CMOR), Dpt. of Neuroscience, School of Medicine, The Johns Hopkins University.
  • Dra. Gabriela Perez, [ICYTAC] – INST. DE CIENCIA Y TECNOLOGIA DE ALIMENTOS CORDOBA –
  • Dr. Ricardo Pautassi, INIMEC, CORDOBA

Subsidios

  • Subsidio Bi-anual de la Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SeCyT-UNC) por el periodo 2014-2016. Tema: Bases Biológicas de desórdenes del neurodesarrollo.
  • Subsidio ANPCyT-FonCyT. PICT 2013-106. Tipo D- Tema: Bases Biológicas de Desórdenes del Neurodesarrollo.

Breve Currículum Vitae

Formación Académica

  • 1995 Microbióloga. Facultad de Ciencias Exactas Fco-Qcas y Naturales. Universidad Nacional de Río Cuarto
  • 2002 Doctora en Ciencias Químicas. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Título de Tesis: Participacion de antigenos extramielínicos en la patogénesis de la Encefalomielitis Alérgica Experimental. Director: Dr.German Roth

Antecedentes en Investigación

  • 1992-1995 Ayudante de Investigación. Dpto. de Biología Molecular. FAc Cs Exactas Fco-Qcas y Naturales. UNRC. Director: Dra. E.E. Machado.
  • 1996-2001 Beca de Iniciación y Perfeccionamiento (CONICET). Dpto. De Química Biológica. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba
  • 2003-2009 Postdoctoral Fellow in the Department of Neuroscience. Johns Hopkins University, Baltimore, Maryland, USA
  • 2009-2015 Visiting Scientist (Faculty) Department of Neuroscience. Johns Hopkins University, Baltimore, Maryland, USA
  • 2010-presente Investigador Adjunto de CONICET. Dpto. De Química Biológica. Facultad de Ciencias Químicas. UNC

Antecedentes Docentes

  • Dpto. De Química Biológica. Facultad de Ciencias Químicas. UNC
  • 1997-1999 Ayudante de Segunda (DS).
  • 2001-2003 Jefe de Trabajos Prácticos (DE).
  • 2010-2015 Profesor Asistente (DS).
  • 2015 Profesor Adjunto DS.

Antecedentes en Gestión

  • 2013-2015 Miembro del Consejo Directivo del CIQUIBIC-CONICET. Departamento de Química Biológica, Facultad de Ciencias Químicas. UNC

Dirección de Tesis Doctorales

  • Desde 2011: Dirección de la tesis doctoral de Maria Laura Bertoldi
  • Desde 2014: Dirección de la tesis doctoral de Maria Inés Zalosnik Figueroa

Dirección de Tesinas de Grado

  • 2003 Lic. en Química Aldo Alejandro Vilcaes. UNC
  • 2011 Lic. En Química Natalia Baez. UNC
  • 2011 Sabrina Gunput. Master en Biomedicina de la Universidad de Leiden (The Netherlands).

 

Research Topic

Neurobiology of autism spectrum disorders

Rett syndrome (RTT) is a neurodevelopmental disorder that shares features of Autism Spectrum Disorders (ASD). In 1999 it was reported that the main cause of RTT consists of mutations in the binding protein methyl-CpG 2 (MECP2). Although RTT is one of the few ASD with a known cause, little is known about the defects that occur during neurodevelopment as a consequence of mutations in Mecp2. Previous work indicates that MeCP2 plays a critical role in the establishment and maintenance of nerve connectivity, participating in the process of neuronal maturation, axonal guidance and activity-dependent synaptic plasticity. Lack of normal MeCP2 during neurodevelopment, alters the expression of molecules involved in the development and maturation of circuits, generating long-term defects in synaptic structure and function. These defects may constitute the neurobiological basis of some behavioral alterations present in these disorders. The overall aim of our project is to define molecular mechanisms by which the lack of Mecp2 generates alterations in the neural connectivity during development, in order to understand the basis of the neuronal pathology that characterizes ASD. To this end, we use MeCP2-null animal models and cell cultures, paradigms of activity in vivo, as well as biological and molecular approaches to: characterize the effect induced by the absence of Mecp2 on the formation and maintenance of neural circuits, identify signaling cascades involved in neural connectivity that are affected Mecp2 and establish causal relationships between structural / functional alterations in hippocampus and cognitive alterations in mutant mice Mecp2. Understanding the mechanisms underlying neuronal compromise caused by mutations in MeCP2 will: 1) provide information on the pathogenic mechanism of ASDs, 2) improve our understanding of brain development and the molecular basis of behavior and 3) generate new potential avenues for therapeutic intervention.

Fellows

Selected Publications

  • Degano, A.L., Park, M.J., Penati J., Lin, Q. and Ronnett G.V. MeCP2 is required for activity-dependent refinement of olfactory circuits. Mol. Cell. Neurosci. 59: 63-75 (2014).
  • Park MJ, Aja S, Li Q, Degano AL, Penati J, Zhuo J, Roe CR, Ronnett GV. Anaplerotic Triheptanoin Diet Enhances Mitochondrial Substrate Use to Remodel the Metabolome and Improve Lifespan, Motor Function, and Sociability in MeCP2-Null Mice. PLoS One. 2014 Oct 9;9(10):e109527.
  • Palmer, A.M.*, Degano, A.L.*, Park M.J., Ramamurty S. and Ronnettt G.V. Normal Mitral Cell Dendritic Development in the Setting of Mecp2 Mutation. Neuroscience 202: 108-116 (2012).
  • Degano, A.L.*, Pasterkamp R.J. and Ronnett G.V. MeCP2 deficiency disrupts axonal guidance, fasciculation, and targeting by altering Semaphorin 3F function. Mol. Cell. Neurosci., 42: 242-255 (2009)
  • Degano, A.L. and Roth, G.A. Synapsin induce proliferation of T-cell lines against myelin basic protein obtained from rats with Experimental Autoimmune Encephalomyelitis. Autoimmunity, 42 (8): 661-666 (2009).

(See more publications-CONICET)

Current Grants

  • Bi-annual grant from the “”Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SeCyT-UNC). 2014-2016. Topic: Biology of Neurodevelopmental disorders
  • Grant ANPCyT-FonCyT. PICT 2013-106. Tipo D- Topic: Biology of Neurodevelopmental disorders

Brief CV

Academic Formation

  • 1990-1995 Degree in Microbiology equivalent to Master in Science, School of Chemistry and Natural Sciences, National University of Rio Cuarto, Cordoba, Argentina – GPA: 9.06 (scale: 0-10)
  • 1996-2002 Ph.D. in Chemical Sciences, School of Chemistry, National University of Cordoba, Argentina. Mentor: German A. Roth, Ph.D. Title: “Role of neuronal antigens in the pathogenesis of Experimental Allergic Encephalomyelitis (EAE)””
  • 2003-2009 Postdoctoral Training, Department of Neuroscience, Johns Hopkins School of Medicine. Mentor: Gabriele V. Ronnett, MD, Ph.D. Title: “Neurobiology of Rett Syndrome”

Research Background

  • 1992-1994 Research Internship. Department of Molecular Biology, Biological Chemistry. Faculty of Physical, Chemical and Natural Sciences. National University of Rio Cuarto (UNRC) Cordoba, Argentina, Mentor: Dra. E.E. Machado de Domenech. “”Protein phosphorilation and lipid metabolism in Trypanosome cruzi”.
  • 1996-2002 Graduate Student. Biological Chemistry Department. Faculty of Chemistry. National University of Cordoba, Argentina, Mentor: Dr. German A. Roth, Ph.D. “Biochemical and immunohistological studies in experimental autoimmune encephalomyelitis (EAE)”.
  • 2003-2009 Postdoctoral Fellow. Johns Hopkins School of Medicine. Department of Neuroscience, Mentor: Dr. Gabriele V. Ronnett. “Mecp2-deficiency…..”.
  • 2009-2015 Visiting Scientist (Faculty) Department of Neuroscience. Johns Hopkins University, Baltimore, Maryland, USA
  • 2010-present Staff Researcher appointed by CONICET (Consejo Nacional de Investigaciones Científicas y Tecnológicas.
  • Biological Chemistry Department. College of Chemical Sciences. National University of Cordoba, Argentina. “Neurobiology of autism spectrum disorders”

Teaching Background

  • 1995-2001 Teaching Assistant. Department of Biological Chemistry, School of Chemical Sciences. National University of Cordoba. Argentina.
  • 2001-2003 Instructor. Department of Biological Chemistry, School of Chemical Sciences. National University of Cordoba. Argentina.
  • 2013-present Assistant Professor, Department of Biological Chemistry, School of Chemical Sciences. National University of Cordoba. Argentina.

Institutional Management Background

  • 2013-2017 Member of the Directive Committee CIQUIBIC-CONICET. Department of Biological Chemistry, School of Chemical Sciences. National University of Cordoba. Argentina.
  • 2015 Member of the Directive Committee CEQUIMAP. School of Chemical Sciences. National University of Cordoba. Argentina.