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Dr. Henry A. Dunn

Dr. Henry A. Dunn

Principal Investigator
Molecular Pharmacology & Neuropsychiatric Disease, Division of Neurodegenerative Disorders

Assistant Professor
Department of Pharmacology and Therapeutics
Max Rady College of Medicine, University of Manitoba

Research Focus

Dr. Henry A. Dunn’s research aims to elucidate the molecular mechanisms underlying neurodevelopmental and neuropsychiatric disease with the goal of facilitating the development of novel therapeutic strategies for a myriad of neurological conditions, including autism spectrum disorder (ASD), anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and epilepsy.

With a prominent focus and expertise on G protein-coupled receptors (GPCRs) and their associated signalling pathways – the pharmaceutical target of over 35% of FDA-approved drugs – Dr. Dunn’s lab utilizes multidisciplinary approaches spanning molecular mechanisms to rodent models, including: molecular pharmacology, biochemistry, cellular & molecular neurobiology, bioinformatics and behavioural neuroscience.

Why is this work important?

Understanding the molecular mechanisms underlying neurodevelopmental and neuropsychiatric disease may guide new therapeutic treatment strategies to improve human quality of life.

What techniques and equipment are used in this laboratory?

  • Immortalized cell-lines, iPSCs, and neuronal culturing
  • Mouse brain microdissection
  • Transcellular GPCR pharmacology
  • Bioluminescence Resonance Energy Transfer (BRET) biosensors
  • BioTek Synergy Neo2 multimode platereader
  • Western blotting and proteomic analysis
  • Confocal fluorescent microscopy

About Dr. Henry Dunn

Dr. Henry A. Dunn is an assistant professor in the Department of Pharmacology and Therapeutics at the University of Manitoba, and a principal investigator at St. Boniface Hospital Albrechtsen Research Centre where he leads the Molecular Pharmacology and Neuropsychiatric Disease Lab.

Dr. Dunn is best known for his work on G protein-coupled receptors (GPCRs): particularly, delineating molecular mechanisms of stress-induced anxiety and depression, and illuminating a novel trans-synaptic pharmacological regulation mechanism with relevance to attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and epilepsy.

These seminal studies have led to a keen interest in the interplay between synaptic adhesion molecules and synaptic GPCRs, including: (1) how these relationships are utilized in synaptic connectivity, neurotransmission and intracellular signalling, and (2) how these interfaces can be exploited for novel drug design in neuropsychiatric disease.

For more information, please contact:

Henry A. Dunn

Principal Investigator
Division of Neurodegenerative Disorders
St. Boniface Hospital Albrechtsen Research Centre
351 Taché Ave
Winnipeg, Manitoba, Canada R2H 2A6

Ives, A.N., Dunn, H.A.., Afsari, H.S., Seckler, H.D.S., Foroutan, MJ., Chavez, E., Melani, R.D., Fellers, R.T., LeDuc, R.D., Thomas, P.M., Martemyanov, K.A., Kelleher, N.L., and Vafabakhsh, R. (2022). Middle-Down Mass Spectrometry Reveals Activity-Modifying Phosphorylation Barcode in a Class C G Protein-Coupled Receptor. J Am Chem Soc, doi: 10.1021/jacs.2c10697

 Cao, Y., Wang, Y., Dunn, H.A., Orlandi, C., Kamasawa, N., Fitzpatrick, D., Li, W., Zeits, C., Hauswirth, W., Martemyanov, K.A. (2020). Interplay between cell adhesion molecules governs synaptic wiring of cone photoreceptors. Proc Natl Acad Sci U S A, doi:10.1073/pnas.2009940117  

 Dunn, H. A. ǂ, Orlandi, Cǂ., & Martemyanov, K. A. ǂ, (2019). Beyond the Ligand: Extracellular and Transcellular Regulation of GPCRs in Physiology and Pharmacology. Pharmacol Rev, doi:10.1124/pr.119.018044

                ǂ co-corresponding authors

Dunn, H. A., Zucca, S., Dao, M., Orlandi, C., & Martemyanov, K. A. (2019). ELFN2 is a postsynaptic cell adhesion molecule with essential roles in controlling group III mGluRs in the brain and neuropsychiatric behavior. Mol Psychiatry. doi:10.1038/s41380-019-0512-3

Dunn, H. A., Zucca, S., Dao, M., Orlandi, C., & Martemyanov, K. A., (2019). Distinct Neuronal Expression Patterns of ELFN1 and ELFN2: Trans-synaptic Modulators of Group III mGluRs. Mol Psychiatry. doi: 10.1038/s41380-019-0593-z

Gupta, S., Abd-Elrahman, K. S., Albaker, A., Dunn, H. A., & Ferguson, S. S. G. (2019). Structural determinants governing beta-arrestin2 interaction with PDZ proteins and recruitment to CRFR1. Cell Signal, 63, 109361. doi:10.1016/j.cellsig.2019.109361

Dunn, H. A., Patil, D. N., Cao, Y., Orlandi, C., & Martemyanov, K. A. (2018). Synaptic adhesion protein ELFN1 is a selective allosteric modulator of group III metabotropic glutamate receptors in trans. Proc Natl Acad Sci U S A, 115(19), 5022-5027. doi:10.1073/pnas.1722498115

Hammad, M. M., Dunn, H. A., & Ferguson, S. S. G. (2018). MAGI proteins can differentially regulate the signaling pathways of 5-HT2AR by enhancing receptor trafficking and PLC recruitment. Cell Signal, 47, 109-121. doi:10.1016/j.cellsig.2018.03.016

Dunn, H. A., Chahal, H. S., Caetano, F. A., Holmes, K. D., Yuan, G. Y., Parikh, R., . . . Ferguson, S. S. G. (2016). PSD-95 regulates CRFR1 localization, trafficking and beta-arrestin2 recruitment. Cell Signal, 28(5), 531-540. doi:10.1016/j.cellsig.2016.02.013

Di Sebastiano, A. R., Fahim, S., Dunn, H. A., Walther, C., Ribeiro, F. M., Cregan, S. P., . . . Ferguson, S. S. (2016). Role of Spinophilin in Group I Metabotropic Glutamate Receptor Endocytosis, Signaling, and Synaptic Plasticity. Journal of Biological Chemistry, 291(34), 17602-17615. doi:10.1074/jbc.M116.722355

 

Hammad, M. M., Dunn, H. A., & Ferguson, S. S. G. (2016). MAGI Proteins Regulate the Trafficking and Signaling of Corticotropin-Releasing Factor Receptor 1 via a Compensatory Mechanism. Journal of Molecular Signaling, 11, 5. doi.org/10.5334/1750-2187-11-5 

Dunn, H. A., & Ferguson, S. S. (2015). PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways. Molecular Pharmacology, 88(4), 624-639. doi:10.1124/mol.115.098509

Hammad, M. M., Dunn, H. A., Walther, C., & Ferguson, S. S. (2015). Role of cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) in regulating the trafficking and signaling of corticotropin-releasing factor receptor 1. Cell Signal, 27(10), 2120-2130. doi:10.1016/j.cellsig.2015.06.004 

Narla, C., Dunn, H. A., Ferguson, S. S., & Poulter, M. O. (2015). Suppression of piriform cortex activity in rat by corticotropin-releasing factor 1 and serotonin 2A/C receptors. Frontiers in Cellular Neuroscience, 9, 200. doi:10.3389/fncel.2015.00200

Walther, C., Caetano, F. A., Dunn, H. A., & Ferguson, S. S. (2015). PDZK1/NHERF3 differentially regulates corticotropin-releasing factor receptor 1 and serotonin 2A receptor signaling and endocytosis. Cell Signal, 27(3), 519-531. doi:10.1016/j.cellsig.2014.12.019

Dunn, H. A., Walther, C., Yuan, G. Y., Caetano, F. A., Godin, C. M., & Ferguson, S. S. (2014). Role of SAP97 in the regulation of 5-HT2AR endocytosis and signaling. Molecular Pharmacology, 86(3), 275-283. doi:10.1124/mol.114.093476

Dunn, H. A., Walther, C., Godin, C. M., Hall, R. A., & Ferguson, S. S. (2013). Role of SAP97 protein in the regulation of corticotropin-releasing factor receptor 1 endocytosis and extracellular signal-regulated kinase 1/2 signaling. Journal of Biological Chemistry, 288(21), 15023-15034. doi:10.1074/jbc.M113.473660

Magalhaes, A. C., Dunn, H., & Ferguson, S. S. (2012). Regulation of GPCR activity, trafficking and localization by GPCR-interacting proteins. Br J Pharmacol, 165(6), 1717-1736. doi:10.1111/j.1476-5381.2011.01552.x

 

Best Oral Presentation – Scripps Florida Research Symposium (2021)

Mark A. Hall Travel Award (2019)

ASPET Blue Ribbon – Experimental Biology (2019)

Best Oral Presentation – Scripps Florida Research Symposium (2018)

CIHR Postdoctoral Fellowship (2017)

Best Poster Presentation – Gairdner Symposium (2014)

Jonathan & Joshua Memorial Graduate Scholarship: Mental Health Research (2013)

Jonathan & Joshua Memorial Graduate Scholarship: Mental Health Research (2012)

CIHR Strategic Training Fellowship (2009)

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