Axonal Transport, Neuraldevelopment and Neurodegeneration

The focus of my lab research is to understand the role of axonal transport and motor proteins in the processes of neural development, axonal pathfinding and the consequences of neurodegeneration asocciated with defects in axonal transport that can lead to the manifestation of neurodegenerative diseases. Using fluorescent-tagged cargos we want to understand the axonal transport properties of receptors, vesicles and organelles. This tracking technique used in combination with biochemistry and pathological characterization of motor protein mutant mice are currently used to identify the role of motor proteins in axonal guidance and development that when impaired can progress into pathologies that may in neurodegenerative diseases. The future goal of the laboratory is to generate a neuronal model from human stem cell differentiation to study axonal transport properties in normal conditions and disease.

  • Principal Investigator

    Phd. Tomás Falzone

     

    Investigador Adjunto (CONICET)

    Jefe de Trabajos Prácticos, UBA.

    tfalzone@fmed.uba.ar

  • Lab Members

     

    Trinidad Saez, Phd. Post-doc. trinidad.mm.saez@gmail.com

    Sol Rodriguez, Biology student. solr343@gmail.com

Grants

PICT 2013-0402. FONCYT Grant, Agencia Nacional de Promoción de la Ciencia

y Tecnología. Argentina.

UBACyT 2014-2017. University of Buenos Aires Grant.

2016 PROLAB (IBRO-LARC). Internacional Cooperation Argentina-Brasil

 

Publications

- Pozo Devoto V & Falzone T.“α-Synuclein and mitochondria biodynamics in Parkinson’s Disease”. Disease Mechanism and Models, Review, Under revision, 2017.

- Pozo Devoto V, Dimopoulous N, Alloatti M, Cromberg L, Otero M, Saez T, Pardi, B, Marin-Burgin, Schinder A, Scassa M, Sevlever G & Falzone T.“αSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s Disease”. Under revision, 2017.

- Lacovich V, Espindola S, Alloatti M, Pozo Devoto M, Cromberg L, Čarná M, Forte G, Gallo J, Bruno L, Stokin G, Avale M & Falzone T“Tau isoforms imbalance impairs the axonal transport of the amyloid precursor protein (APP) in human neurons”, Journal of Neuroscience. Jan 4;37(1):58-69., 2017.

- Medina C; Biris O, Falzone T, Zhang X, Zimmerman A, Bearer E.“Hippocampal to basal forebrain transport of Mn2+ is impaired by deletion of KLC1, a subunit of the conventional kinesin microtubule-based motor”. Neuroimage, Jan 15;145:44-57 2017.

- LaSpina F, Molina L, Romarowski A, Vitale A, Falzone T, Krapf D, Hirohashi N, Buffone M. “Mouse sperm begin to undergo acrosomal exocytosis in the upper isthmus of the oviduct”. Developmental Biology. Feb 10; Mar 15;411(2):172-82, 2016.

- Otero G, Alloatti M, Cromberg L, Almenar-Queralt A, Encalada S, Pozo Devoto V, Goldstein L, Falzone T.“Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function”. Journal of Cell Science,April 1;127, 1537-49, 2014.

- Almenar-Queralt A, Falzone T, Shen Z, Arreola A, Niederst E, Kim S, Briggs S, Williams S, Goldstein L. “UV Accelerates Amyloid Precursor Protein (APP) Processing and Disrupts APP Axonal Transport”. Journal of Neuroscience,Feb 26;34(9):3320-39, 2014.

Falzone T & Stokin G. "Imaging amyloid precursor protein in vivo: an axonal transport assay". Methods in Molecular Biology, 846:295-303, 2012.

Falzone T, Gunawardena S, McCleary D, Reis G, Goldstein L. “Kinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies.”. Human Molecular Genetics, Nov 15;19(22):4399-408, 2010.

Falzone T, Stokin G, Lillo C, Rodrigues E, Westerman E, Williams D, Goldstein L. “Axonal Stress Kinase Activation and Tau Misbehavior Induced by Kinesin-1 Transport Defects”. Journal of Neuroscience. 29(18):5758-67. May 6, 2009.

- Stokin G, Lillo C, Falzone T, Brusch R, Rockenstein E, Mount S, Raman R, Davies P, Masliah E, Williams D, Goldstein L. “Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease”. Science, 307(5713):1282-8, Feb 25, 2005.

Falzone T, Gelman D, Young J, Grandy D, Low M and Rubinstein M. “Absence of DopamineD4 Receptors Results in Enhanced Reactivity to Unconditioned, But not Conditioned, Fear”.European Journal of Neuroscience, (1):158-164. Jan 15, 2002.

- Rubinstein M, Phillips T, Bunzow J, Falzone T, Dziewczapolski G, Zhang G, Fang Y, Larson J, McDougall J, Chester J, Saez C, Pugsley T, Gershanik O, Low M and Grandy D. “Mice Lacking Dopamine D4 Receptors Are Supersensitivite to Ethanol, Cocaine, and Methamphetamine”. Cell, Vol. 90:991-1001, Sep 19, 1997.

 

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