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MRC Toxicology Unit

 

Unit Programme: Neuronal model systems for examining toxicity

Programme Leader Track: Dr Lia Panman

 

Neurons producing the neurotransmitter dopamine serve important brain functions and are implicated in disorders including Parkinson’s disease. This neuronal population is highly diverse consisting of several molecular and functional distinct subpopulations that innervate specific brain areas. Lia’s research team is focussed on understanding processes involved in dopamine neuron subtype diversification, function and target innervation. Her team is using ES cells to elucidate novel pathways involved in dopamine neuron subtype specification during mouse and human embryonic development. ES cell derived cultures enriched for substantia nigra dopaminergic neurons are used to model the selective vulnerability of dopaminergic neurons to toxic insults as observed in Parkinson’s disease. The team is using system biology approaches to elucidate genes and pathways that mediate the cellular responses that trigger the selective degeneration of substantia nigra neurons upon toxic insults. Another research line in Lia’s team investigates the processes involved in establish dopaminergic connectivity using transgenic mouse models.

 

Key Publications

Panman L*., Papathanou M., Laguna A., Oosterveen T., Volakakis N., Acampora D., Kurtsdotter I., Yoshitake T., Kehr J., Joodmardi E., Muhr J., Simeone A., Ericson J., Perlmann T*. (2014). Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons. Cell reports 8(4), 1018-1025. *Corresponding author

Mong J*., Panman L*., Alekseenko Z., Kee N., Stanton LW, Ericson J. and Perlmann T. (2014). Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells. Stem Cells 32(3), 609-622. *Joint first author

Panman L., Andersson E., Hedlund E., Kee N., Mong J., Uhde C., Deng Q., Alekseenko Z., Sandberg R., Stanton L.W., Ericson J., Perlmann T. (2011). Transcription factor-induced lineage selection of stem cell derived neural progenitor cells. Cell Stem Cell 8(6), 663-675.

Panman L., Perlmann T. (2011). Tracing lineages to uncover neuronal identity. BMC Biology 9, 51

Deng Q., Andersson E., Hedlund E., Alekseenko Z., Panman L., Millonig J., Ericson J., Perlmann T.  (2011). Specific and integrated roles of Lmx1a, Lmx1b and Phox2a in ventral midbrain development. Development 138, 3399-3408.

Volakakis N., Kadkhodaei B., Joodmardi E., Wallis K., Panman L., Silvaggi J., Spiegelman B.M., Perlmann T. (2010). NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection. PNAS 107(27), 12317-22.