Associate Researcher CONICET / Adjunct Professor UNC
Phone: +54 351 5353855 x 3418
Neurobiology of autism spectrum disorders
Right 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.
- 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).
- Bi-annual grant from the “”Ministry of Science and Technology of the National University of Córdoba (SeCyT-UNC). 2014-2016. Topic: Biology of Neurodevelopmental disorders
- Grant ANPCyT-FonCyT. PICT 2013-106. Tipo D- Topic: Biology of Neurodevelopmental disorders
- 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”
- 1992-1994 Research Internship. Department of Molecular Biology, Biological Chemistry. Faculty of Physical, Chemical and Natural Sciences. National University of Rio Cuarto (UNCRC) Cordoba, Argentina, Mentor: Dr. È.é. Machado de Domenech. “”Protein phosphorilation and lipid metabolism in Trypanosome cruzi”.
- 1996-2002 Graduate Student. Biological Chemistry Department. College of Chemical Sciences. 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 (National Council of Scientific and Technological Research.
- Biological Chemistry Department. College of Chemical Sciences. National University of Cordoba, Argentina. “Neurobiology of autism spectrum disorders”
- 1995-2001 Teaching Assistant. Department of Biological Chemistry, College of Chemical Sciences. National University of Cordoba. Argentina.
- 2001-2003 Instructor. Department of Biological Chemistry, College of Chemical Sciences. National University of Cordoba. Argentina.
- 2013-present Assistant Professor, Department of Biological Chemistry, College of Chemical Sciences. National University of Cordoba. Argentina.
Institutional Management Background
- 2013-2017 Member of the Directive Committee CIQUIBIC-CONICET. Department of Biological Chemistry, College of Chemical Sciences. National University of Cordoba. Argentina.
- 2015 Member of the Directive Committee CEQUIMAP. College of Chemical Sciences. National University of Cordoba. Argentina.