Professional Education

  • Diploma, University of Belgrade (2005)
  • Doctor of Philosophy, Ecole Polytechnique Federale Lausanne (2011)

Stanford Advisors


All Publications

  • Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS NATURE NEUROSCIENCE Jovicic, A., Mertens, J., Boeynaems, S., Bogaert, E., Chai, N., Yamada, S. B., Paul, J. W., Sun, S., Herdy, J. R., Bieri, G., Kramer, N. J., Gage, F. H., Van Den Bosch, L., Robberecht, W., Gitler, A. D. 2015; 18 (9): 1226-?

    View details for DOI 10.1038/nn.4085

    View details for Web of Science ID 000360292600009

  • The novel Parkinson's disease linked mutation G51D attenuates in vitro aggregation and membrane binding of alpha-synuclein, and enhances its secretion and nuclear localization in cells HUMAN MOLECULAR GENETICS Fares, M., Ait-Bouziad, N., Dikiy, I., Mbefo, M. K., Jovicic, A., Kiely, A., Holton, J. L., Lee, S., Gitler, A. D., Eliezer, D., Lashuel, H. A. 2014; 23 (17): 4491-4509


    A novel mutation in the α-Synuclein (α-Syn) gene "G51D" was recently identified in two familial cases exhibiting features of Parkinson's disease (PD) and multiple system atrophy (MSA). In this study, we explored the impact of this novel mutation on the aggregation, cellular and biophysical properties of α-Syn, in an attempt to unravel how this mutant contributes to PD/MSA. Our results show that the G51D mutation significantly attenuates α-Syn aggregation in vitro. Moreover, it disrupts local helix formation in the presence of SDS, decreases binding to lipid vesicles C-terminal to the site of mutation and severely inhibits helical folding in the presence of acidic vesicles. When expressed in yeast, α-Syn(G51D) behaves similarly to α-Syn(A30P), as both exhibit impaired membrane association, form few inclusions and are non-toxic. In contrast, enhanced secreted and nuclear levels of the G51D mutant were observed in mammalian cells, as well as in primary neurons, where α-Syn(G51D) was enriched in the nuclear compartment, was hyper-phosphorylated at S129 and exacerbated α-Syn-induced mitochondrial fragmentation. Finally, post-mortem human brain tissues of α-Syn(G51D) cases were examined, and revealed only partial colocalization with nuclear membrane markers, probably due to post-mortem tissue delay and fixation. These findings suggest that the PD-linked mutations may cause neurodegeneration via different mechanisms, some of which may be independent of α-Syn aggregation.

    View details for DOI 10.1093/hmg/ddu165

    View details for Web of Science ID 000340238200003

  • TDP-43 in ALS: stay on target…almost there. Neuron Jovicic, A., Gitler, A. D. 2014; 81 (3): 463-465


    ALS is associated with RNA processing impairments involving the RNA-binding protein TDP-43. Pioneering a novel RNA beacon to illuminate RNA trafficking in neurons, Alami et al. (2014) discover a cytoplasmic function for TDP-43, suggesting a new disease mechanism.

    View details for DOI 10.1016/j.neuron.2014.01.034

    View details for PubMedID 24507183

  • Exome sequencing to identify de novo mutations in sporadic ALS trios. Nature neuroscience Chesi, A., Staahl, B. T., Jovicic, A., Couthouis, J., Fasolino, M., Raphael, A. R., Yamazaki, T., Elias, L., Polak, M., Kelly, C., Williams, K. L., Fifita, J. A., Maragakis, N. J., Nicholson, G. A., King, O. D., Reed, R., Crabtree, G. R., Blair, I. P., Glass, J. D., Gitler, A. D. 2013; 16 (7): 851-855


    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease whose causes are still poorly understood. To identify additional genetic risk factors, we assessed the role of de novo mutations in ALS by sequencing the exomes of 47 ALS patients and both of their unaffected parents (n = 141 exomes). We found that amino acid-altering de novo mutations were enriched in genes encoding chromatin regulators, including the neuronal chromatin remodeling complex (nBAF) component SS18L1 (also known as CREST). CREST mutations inhibited activity-dependent neurite outgrowth in primary neurons, and CREST associated with the ALS protein FUS. These findings expand our understanding of the ALS genetic landscape and provide a resource for future studies into the pathogenic mechanisms contributing to sporadic ALS.

    View details for DOI 10.1038/nn.3412

    View details for PubMedID 23708140

  • Exome sequencing to identify de novo mutations in sporadic ALS trios NATURE NEUROSCIENCE Chesi, A., Staahl, B. T., Jovicic, A., Couthouis, J., Fasolino, M., Raphael, A. R., Yamazaki, T., Elias, L., Polak, M., Kelly, C., Williams, K. L., Fifita, J. A., Maragakis, N. J., Nicholson, G. A., King, O. D., Reed, R., Crabtree, G. R., Blair, I. P., Glass, J. D., Gitler, A. D. 2013; 16 (7): 851-U98

    View details for DOI 10.1038/nn.3412

    View details for Web of Science ID 000321180900017

  • Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes JOURNAL OF NEUROSCIENCE Jovicic, A., Roshan, R., Moisoi, N., Pradervand, S., Moser, R., Pillai, B., Luthi-Carter, R. 2013; 33 (12): 5127-5137


    MicroRNAs (miRNAs) have been shown to play important roles in both brain development and the regulation of adult neural cell functions. However, a systematic analysis of brain miRNA functions has been hindered by a lack of comprehensive information regarding the distribution of miRNAs in neuronal versus glial cells. To address this issue, we performed microarray analyses of miRNA expression in the four principal cell types of the CNS (neurons, astrocytes, oligodendrocytes, and microglia) using primary cultures from postnatal d 1 rat cortex. These analyses revealed that neural miRNA expression is highly cell-type specific, with 116 of the 351 miRNAs examined being differentially expressed fivefold or more across the four cell types. We also demonstrate that individual neuron-enriched or neuron-diminished RNAs had a significant impact on the specification of neuronal phenotype: overexpression of the neuron-enriched miRNAs miR-376a and miR-434 increased the differentiation of neural stem cells into neurons, whereas the opposite effect was observed for the glia-enriched miRNAs miR-223, miR-146a, miR-19, and miR-32. In addition, glia-enriched miRNAs were shown to inhibit aberrant glial expression of neuronal proteins and phenotypes, as exemplified by miR-146a, which inhibited neuroligin 1-dependent synaptogenesis. This study identifies new nervous system functions of specific miRNAs, reveals the global extent to which the brain may use differential miRNA expression to regulate neural cell-type-specific phenotypes, and provides an important data resource that defines the compartmentalization of brain miRNAs across different cell types.

    View details for DOI 10.1523/JNEUROSCI.0600-12.2013

    View details for Web of Science ID 000316553800007

    View details for PubMedID 23516279

  • MicroRNA-22 (miR-22) overexpression is neuroprotective via general anti-apoptotic effects and may also target specific Huntington's disease-related mechanisms. PloS one Jovicic, A., Zaldivar Jolissaint, J. F., Moser, R., Silva Santos, M. d., Luthi-Carter, R. 2013; 8 (1)


    Whereas many causes and mechanisms of neurodegenerative diseases have been identified, very few therapeutic strategies have emerged in parallel. One possible explanation is that successful treatment strategy may require simultaneous targeting of more than one molecule of pathway. A new therapeutic approach to have emerged recently is the engagement of microRNAs (miRNAs), which affords the opportunity to target multiple cellular pathways simultaneously using a single sequence.We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington's disease (histone deacetylase 4 (HDAC4), REST corepresor 1 (Rcor1) and regulator of G-protein signaling 2 (Rgs2)) and its diminished expression in Huntington's and Alzheimer's disease brains. We then tested the hypothesis that increasing cellular levels of miRNA-22 would achieve neuroprotection in in vitro models of neurodegeneration. As predicted, overexpression of miR-22 inhibited neurodegeneration in primary striatal and cortical cultures exposed to a mutated human huntingtin fragment (Htt171-82Q). Overexpression of miR-22 also decreased neurodegeneration in primary neuronal cultures exposed to 3-nitropropionic acid (3-NP), a mitochondrial complex II/III inhibitor. In addition, miR-22 improved neuronal viability in an in vitro model of brain aging. The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38) and tumor protein p53-inducible nuclear protein 1 (Tp53inp1). Moreover, HD-specific effects comprised not only targeting HDAC4, Rcor1 and Rgs2 mRNAs, but also decreasing focal accumulation of mutant Htt-positive foci, which occurred via an unknown mechanism.These data show that miR-22 has multipartite anti-neurodegenerative activities including the inhibition of apoptosis and the targeting of mRNAs implicated in the etiology of HD. These results motivate additional studies to evaluate the feasibility and therapeutic efficacy of manipulating miR-22 in vivo.

    View details for DOI 10.1371/journal.pone.0054222

    View details for PubMedID 23349832

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