Lab Projects

We study the molecular mechanisms underlying tauopathies (Alzheimer’s disease and related dementias) and Parkinson’s disease (PD). As experimental models we use transgenic mice – tauopathy or PD models- to evaluate potential molecular therapies capable of reversing degenerative processes. Additionally, we use cultured neurons to analyze neuronal survival and dysfunction, and to elucidate mechanisms related to neuronal death processes.

-Post-transcriptional regulation of tau
Our projects are mainly focused on studying the post-transcriptional processing of the MAPT gene, which codes for the microtubule-associated protein tau, and evaluating the functional consequences in models of neurodegeneration.
The Tau protein is expressed mainly in neurons, and under normal conditions it participates in the stabilization of microtubules and in axonal transport. Alzheimer’s disease (AD) and other similar neurodegenerative diseases are classified within the group of tauopathies, due to the abnormal accumulation of Tau protein in the brain of affected patients. In our laboratory, we optimized the use of a molecular strategy to correct defects due to abnormal Tau splicing, through the expression of heterologous RNA fragments capable of coupling with the endogenous messenger and generating a functional RNA chimera (Avale et al., 2013). This strategy allowed us to study the consequences of the imbalance of tau isoforms on axonal transport mechanisms in human neurons (Lacovich et al., 2017), the effects on the development of cognitive deficits in a murine model of taupatia (Espindola et al., 2018 ) and motor deficits related to parkinsonism (Damianich et al 2021). We also optimized the trans-splicing intervention for phenotypic rescue in a preclinical model (Muñiz et al 2022).
We are currently also evaluating the functional consequences of Tau post-transcriptional silencing, developing new tools based on artificially designed microRNAs.

-Predictive phenotypes and environmental effects in the development of taupaties
We investigate early phenotypes (biochemical, behavioral or sensory), which may be predictive of neurodegenerative processes associated with dysfunctions in tau and/or other target molecules, as well as environmental modifications that may impact on the development of Tau pathology.
We study how certain conditions can affect the pathological accumulation of tau and impact the manifestation of early or late phenotypes in models of tauopathy (sleep disorders, olfactory function, drugs, diet).

-Translational research
Our laboratory is part of the Argentine Consortium for Translational Research in Primary Taupathies (https://ingebi-conicet.gov.ar/caitaup/) whose objective is to generate a repository of clinical, genetic, molecular and histopathological data of patients with Progressive Supranuclear Palsy (PSP) and corticobasal degeneration (CBD) in Argentina.