Keywords

Folding and targeting of neurotransmitter transporters and GPCRs; Intellectual Disability; Molecular Mechanisms of Pharmacological Action; Mutation, Missense; Neuropharmacology; Neuropsychopharmacology; Neurotransmitter Transporters; Neurotransmitter Uptake Inhibitors; Parkinsonian Disorders

Research interests

My research focuses on rare disease variants occurring in neurotransmitter transporters (NTTs).

We probe both the functional consequences, as well as various molecular aspects (e.g. protein folding), of NTT mutations linked to disorders including epilepsy, infantile parkinsonism & intellectual disability. We also explore novel therapeutic avenues in the pharmacological rescue of such pathological variants using small molecules like chemical/pharmacological chaperones & allosteric modulators. 

Other ongoing projects in the lab centre around the molecular structure-function relationships of monoamine transporters and their interactions with antidepressant and psychostimulant drugs.

https://www.mdpi.com/journal/cells/special_issues/neuro_trans

Techniques, methods & infrastructure

Pharmacological assays (uptake, binding and efflux), molecular biology and biochemistry (site-directed mutagenesis, DNA/RNA purification, cell surface biotinylation, immunoblotting, immunocytochemistry), cell culture (primary neuronal cultures, established cell lines, transient and stable transfections, siRNA-induced knock-down…), microscopy (confocal laser scanning microscopy and förster resonance energy transfer (FRET), collaborative projects investigating transporters in flies (Drosophila melanogaster).  

Grants

• Pharmacological rescue of creatine transporter-1 variants (2018)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Principal Investigator
• Pharmacochaperoning of the dopamine transporter (2014)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Principal Investigator

Selected publications

1. Bhat, S. et al., 2021. Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits. Pharmacology & Therapeutics, 222, p.107785. Available at: http://dx.doi.org/10.1016/j.pharmthera.2020.107785.
2. Farr, C.V. et al., 2020. The Creatine Transporter Unfolded: A Knotty Premise in the Cerebral Creatine Deficiency Syndrome. Frontiers in Synaptic Neuroscience, 12. Available at: http://dx.doi.org/10.3389/fnsyn.2020.588954.
3. El-Kasaby, A. et al., 2019. Rescue by 4-phenylbutyrate of several misfolded creatine transporter-1 variants linked to the creatine transporter deficiency syndrome. Neuropharmacology, 161, p.107572. Available at: http://dx.doi.org/10.1016/j.neuropharm.2019.03.015.
4. Asjad, H.M.M. et al., 2017. Pharmacochaperoning in a Drosophila model system rescues human dopamine transporter variants associated with infantile/juvenile parkinsonism. Journal of Biological Chemistry, 292(47), pp.19250–19265. Available at: http://dx.doi.org/10.1074/jbc.M117.797092.
5. Kern, C. et al., 2017. The N Terminus Specifies the Switch between Transport Modes of the Human Serotonin Transporter. Journal of Biological Chemistry, 292(9), pp.3603–3613. Available at: http://dx.doi.org/10.1074/jbc.m116.771360.