Brain mechanisms of GHB and GABAergic signalling in the Wellendorph Lab 

Our lab is devoted to understanding brain mechanisms involving the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and its metabolite GHB (γ-hydroxybutyric acid). We use biochemical and pharmacological analyses in cells, tissues and whole organisms to elucidate the role of GHB and GABA targets in brain dysfunction. 

 

 

 

 

 

 

 

A main focus is to dissect the functional role of the calcium/calmodulin-dependent protein kinase 2 alpha (CaMKIIa) which we have uncovered as the long-sought-after high-affinity binding site for GHB in the mammalian brain. This involves dissecting molecular mechanisms using highly selective compounds generated in-house, and investigating their potential therapeutic potential in e.g. acute brain injury.

Another focus area is GABAA receptors and their role in brain excitability governed by tonic inhibition using novel ligands and pharmacological assays.

We also work on structural and pharmacological aspects of SLC6A GABA and glycine transporters including how to inhibit them in novel ways. 

 

 

 

 

 

 

 

 

 

 

  1. Identification of the ubiquitous neuronal signalling molecule CaMKIIα as the physiological target for GHB
  2. Demonstration of the potential effect of GHB analogues in ischemic stroke
  3. Identification of novel ligands for extrasynaptic GABAA receptors
  4. Structure-function of GABA transporters

    Linked articles:

    1. Leurs U, Klein AB, McSpadden ED, Griem-Krey N, Solbak SMØ, Houlton J, Villumsen IS, Vogensen SB, Hamborg, L, Gauger SJ, Palmelund LB, Larsen ASG, Shehata MA, Kelstrup CD, Olsen, JV, Bach A, Burnie RO, Kerr S, Gowing EK, Teurlings SMW, Chi CC, Gee CL, Frølund B, Kornum BR,  van Woerden GM, Clausen RP, Kuriyan J, Clarkson AN & Wellendorph P (2021). GHB confers neuroprotection through specific interaction with the CaMKIIα hub domain. Proc. Natl. Acad. Sci USA 118 No 31 e2108079118. https://doi.org/10.1073/pnas.2108079118 


    2. Griem-Krey N, Clarkson AN, Wellendorph P. CaMKIIa as a promising drug target for ischemic grey matter (2022). Brain Sci. 29;12(12):1639. doi: 10.3390/brainsci12121639


    3. Falk-Petersen CB, Rostrup F, Löffler R, Buchleihtner S, Harpsøe K, Gloriam D, Frølund B, Wellendorph P (2021). Molecular determinants underlying delta selective compound 2 activity at d-containing GABAA receptors. Mol. Pharmacol. 100(1), 46-56. doi: 10.1124/molpharm.121.000266
      Free e-prints 

    4. Shahsavar A & Wellendorph P (2023). GABA transport cycle: Beyond a GAT feeling. Nat. Struct. Mol. Biol. DOI: 10.1038/s41594-023-01032-5

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

    2023

    Boat trip 2023Boat trip 
     

    2022

    Group dinner December 2022Group photo from the December dinner

    Group picture Wellendorph groupTeam building

    2021

    Group event
    Paddle tennis 

    2019

    Group event Escape Room Dec 2019

     

     

    Listen to our podcast on Research Pod.

     

     

     

     

     

     

     

     

     

     

     

     

    Group leader

    Group Leader

    Petrine Wellendorph
    Professor

    Phone +45 3533 6397
    pw@sund.ku.dk

    Current group members

    Name Title Phone E-mail
    Mikkelsen, Amalie Nikita List Research Assistant E-mail
    Westi, Emil Winther PhD Fellow E-mail
    Mortensen, Jonas Sigurd Postdoc +4535335369 E-mail
    Wilhelmsen, Kristine Egested Sloth PhD Fellow E-mail
    Gauger, Stine Juul PhD Fellow +4535327111 E-mail