Ph.D., Columbia University, 1995
In experimental work with fly, mouse, cell culture, and human postmortem tissue, we are working to uncover mechanisms of neurodegeneration that underlie amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We are exploring the possibility that a “reawakening” of transposons -- dormant repetitive sequences in the DNA of certain brain cells -- may be responsible for causing cell death.
Research in Josh Dubnau’s lab is concentrated on two different questions. First, Dubnau and his team are investigating mechanisms of memory using Drosophila as a model system. A second area of research is focused on uncovering mechanisms of neurodegeneration that underlie amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Work in the Dubnau lab has suggested a novel hypothesis to explain neurodegeneration in these disorders. They discovered that awakening retrotransposons in the genome of some brain cells might be responsible for causing cell death. Retrotransposons are virus-like repetitive elements that are encoded in the genome and are capable of replicating and inserting into new chromosomal positions. This can lead to DNA damage and cell death by a process known as apoptosis. The lab is investigating this hypothesis for ALS/FTLD using a multidisciplinary approach that includes experimental work with fly, mouse, cell culture, and human postmortem tissue. Computational analyses of genomic data are performed in collaboration with Molly Hammell’s group. If the retrotransposon hypothesis is correct, it will change the trajectory of neurodegeneration research and have obvious clinical impact. Retrotransposon RNAs and proteins are promising new diagnostic markers and potentially important therapeutic targets.
Li, W., Prazak, L., Chatterjee, N., Grüninger, S., Krug, L., Theodorou, D., and Dubnau, J. 2013. Activation of transposable elements during aging and neuronal decline in Drosophila. Nat. Neurosci. 16: 529–531.
Li,W., Cressy, M., Qin, H., Fulga, T., Van Vactor, D., and Dubnau, J. 2013. microRNA-276a functions in ellipsoid body and mushroom body neurons for naïve and conditioned odor avoidance in Drosophila. J. Neurosci. 33: 5821–5833.
Li, W., Prazak, L., Jin, Y., Hammel, M., and Dubnau, J. 2012. Transposable elements in TDP-43-mediated neurodegenerative disorders. PLoS One 7(9) e44099.
Qin, H., Cressy, M., Li, W., Coravos, J., Izzi, S., and Dubnau, J. 2012. Gamma neurons mediate dopaminergic input during aversive olfactory memory formation in Drosophila. Curr. Biol. 22: 608–614.
Blum, A., Li, W., Cressy, M. and Dubnau, J. 2009. Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types. Curr. Biol. 19: 1341–1350.
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