Detail

Keywords

Biochemistry; Dopamine; Molecular Biology; Neurodegeneration; Neuropharmacology; Neurotransmitter Transporters; Parkinson Disease

Research group(s)

• Molecular Pharmacology
  Members:
  Thomas Steinkellner

Research interests

Our primary research goal is to investigate the cellular determinants that influence selective vulnerability or resistance in neurodegenerative diseases such as Parkinson’s disease. My lab aims to determine factors that make specific neuronal populations either more vulnerable or more resistant to neurodegeneration in order to identify potential targets for therapeutic intervention of these hitherto incurable diseases.

Secondly, my lab is interested in how psychostimulants such as amphetamines modulate synaptic transmission and hijack neural circuits that lead to drug addiction and dependence.

Lastly, my lab is interested in developing novel molecular tools for neuroscience research using genetic techniques that can be used to better visualize perturbations during ongoing neurodegeneration or after substance abuse.

Techniques, methods & infrastructure

Genetic mouse models (Cre recombinase expressing mouse lines; conditional knockouts), viral vectors (adeno-associated viruses; AAVs), CRISPR/Cas9 technology (knockouts and knock-ins), neuronal tract tracing, cell lines and primary neuronal cell culture (transfections, transductions), postmortem human brain tissue, molecular biology (cloning, site-directed mutagenesis, PCRs), biochemistry, (immunoprecipitations, pulldown assays, Western blots), neurochemistry (HPLC), histology (immunohistochemistry, mRNA in situ hybridizations in rodent and human brain sections), microscopy, pharmacology (radiotracer flux assays, behavioral pharmacology). 

Grants

• Role of SOX6 in parkinsonism and neurodevelopmental disease (2023)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Principal Investigator
• Becoming ‘bilingual’ through transmitter co-release (2022)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Principal Investigator
• Transmitter Co-Release From A Midbrain Cholinergic Nucleus In Mood Disorders (2022)
  Source of Funding: Brain & Behavior Research Foundation, NARSAD Young Investigator
  Principal Investigator
• VGLUT2 function in dopamine neuron vulnerability (2022)
  Source of Funding: FWF (Austrian Science Fund), stand-alone project
  Principal Investigator
• Regulation of VGLUT2 in aging-related neurodegenerative disorders (2018)
  Source of Funding: National Institutes of Health (NIH), K99
  Principal Investigator
• Role of dopamine-glutamate co-release in Parkinson s disease (2015)
  Source of Funding: FWF (Austrian Science Fund), Schroedinger Program
  Principal Investigator

Selected publications

1. Steinkellner, T. et al., 2018. Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons. Journal of Clinical Investigation, 128(2), pp.774–788. Available at: http://dx.doi.org/10.1172/JCI95795.
2. Steinkellner, T. et al., 2022. ‘Dopamine neurons exhibit emergent glutamatergic identity in Parkinson’s disease’, Brain, 145(3), pp. 879–886. Available at: http://dx.doi.org/10.1093/brain/awab373.
3. Zell, V., Steinkellner, T. et al., 2020. VTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release. Neuron, 107(5), pp.864–873.e4. Available at: http://dx.doi.org/10.1016/j.neuron.2020.06.011.
4. Garcia Moreno, S.I. et al. (2024) ‘Viral overexpression of human alpha-synuclein in mouse substantia nigra dopamine neurons results in hyperdopaminergia but no neurodegeneration’, Experimental Neurology, 382, p. 114959. Available at: https://doi.org/10.1016/j.expneurol.2024.114959.
5. Steinkellner, T. et al., 2015. Amphetamine Action at the Cocaine- and Antidepressant-Sensitive Serotonin Transporter Is Modulated by  CaMKII. Journal of Neuroscience, 35(21), pp.8258–8271. Available at: http://dx.doi.org/10.1523/JNEUROSCI.4034-14.2015.