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Hsiao-Huei Chen, PhD

Hsiao-Huei Chen

Senior Scientist, Neuroscience Program
Ottawa Hospital Research Institute
Professor, Medicine
University of Ottawa
Professor (adj), Cellular and Molecular Medicine
Professor, Graduate program of Neuroscience
University of Ottawa
Professor, Graduate program of Pathology and Experimental Medicine (PhD)
University of Ottawa
Professor (adj), Neurobiology and Cognitive Science Center
National Taiwan University

Research Interests

My laboratory is working to identify common molecular links between metabolic disorders (diabetes and atherosclerosis) and stroke, anxiety and Alzheimer’s disease in order to develop common therapies to restore healthy brain function. The techniques used in the laboratory include molecular biology, cell culture, in vitro (brain slice) and in vivo electrophysiological recording and pharmacological intervention. The animal models used include several cell-type specific transgenic or knockout mice, middle cerebral artery occlusion and photothrombosis for stroke studies, bone marrow transplantation for atherosclerosis.

More recently, we have also tied metabolic syndromes to other neurological disorders, including schizophrenia and autism. We have identified new genetic models of these disorders. Using AAV viral vectors and optogenetic methods together with patch-clamp recording of acute brain slices, we are investigating how neural circuits involved in these two disorders are affected in our genetic knockout mouse models. Pharmacological intervention using these preclinical mouse models is being evaluated by electrophysiology, behaviour studies and biochemical analysis of cellular signalling. Combining optogenetic stimulation with in vivo electrophysiological recording, neural circuit deficits and treatment for Autism disorders is being investigated and we welcome skilled researchers who are ambitious to take on this challenge.

Brief Biography

Hsiao-Huei Chen, PhD, Senior Scientist & Professor
 Ph.D.         Committee on Virology, University of Chicago, 1995
 BS.            Zoology, National Taiwan University, Taipei, Taiwan, 1989  

2003-2004       Senior Research Associate, Cardiovascular Institute, University of Pittsburgh
1997-2003       Research Associate, Department of Neurobiology, University of Pittsburgh. 
1995-1996       Postdoctoral fellow, Department of Neurology, University of Pittsburgh.   

2014-2018       Mid-Career Award, Heart and Stroke Foundation of Ontario (ranked #1)
2009-2014       New Investigator Award, Heart and Stroke Foundation of Canada
2009-2014       New Investigator Award, Canadian Institutes of Health Research (declined to accept the NIA,                                             HSFC)
2009-2014       Early Researcher Award, Ontario Ministry of Research and Innovation
2009                 Henry J. M. Barnett Research Scholarship award, The Heart and Stroke Foundation of Canada 
1999-2002     National Research Service Award, National Institutes of Health (USA)(National Institute of Neurological Diseases and Stroke) 1997-2000 National Research Service Award, National Institutes of Health (USA) (National Heart, Lung &                           Blood Institute)(terminated in 19999 for relocation)
1997-2000 Postdoctoral fellowship, American Heart Association (declined to accept the NRSA, NIH)

Selected Publications

My Bibliography:* Corresponding author.

1.       Stewart AFR, Chen HH*. NMDA receptor functions altered by neuronal PTP1B activation in neurological disorders. Neural Regeneration Research. (2022) DOI:10.4103/1673-5374.335793   (Impact Factor = 5.2)

2.       Vilmundarson RO,  Duong A, Soheili F, Chen HH, Stewart AFR. IRF2BP2 3'UTR Polymorphism Increases Coronary Artery Calcification in Men. Front Cardiovasc Med. (2021). doi:10.3389/fcvm.2021.687645. (Impact Factor = 4.8)

3. Zhang L, Qin Z, Sharmin F, Lin W, Ricke KM, Stewart AFR, Chen HH*. Tyrosine phosphatase PTP1B impairs presynaptic NMDA receptor-mediated plasticity in a mouse model of Alzheimer’s disease. Neurobiology of Disease. (2021) doi.org/10.1016/j.nbd.2021.105402
(Impact Factor = 5.6)

4. Qin Z, Zhang L, Stewart AFR, Chen HH*. Ketamine’s schizophrenia-like effects are prevented by targeting PTP1B.  Neurobiology of Disease. (2021) doi.org/10.1016/j.nbd.2021.105397
(Impact Factor = 5.6)

5. Cruz SA, Qin Z, Ricke KM, Stewart AFR, Chen HH*. Neuronal tyrosine phosphatase PTP1B hinders sensory-motor functional recovery and causes affective disorders in two different focal ischemic stroke models. Neural Regeneration Research(2021). 16(1):129-136 
(Impact Factor = 5.13)

6. Qin Z, Zhang L, Cruz SA, Stewart AFR, Chen HH*. Activation of tyrosine phosphatase PTP1B in pyramidal neurons impairs endocannabinoid signaling by tyrosine receptor kinase trkB and causes schizophrenia-like behaviors in mice. Neuropsychopharmocology. (2020) Jul 1. doi: 10.1038/s41386-020-0755-3
(Impact Factor = 7.9)

7.  Stewart AFR, Chen HH*. Perspective: Activation of tyrosine phosphatases in the progression of Alzheimer’s disease. Neural Regeneration Research (2020) 15(12):2245-2246.
(Impact Factor = 5.13)  

8. Zhang L, Qin Z, Ricke KM, Cruz SA, Stewart AFR, Chen HH*. Hyperactivated PTP1B phosphatase in parvalbumin neurons alters anterior cingulate inhibitory circuits and induces autism-like behaviors. Nature Communications. 2020 Feb 24;11(1):1017 p1-15.
(Impact Factor = 14.9).

9. Ricke KM, Cruz SA, Qin Z, Farrokhi K, Sharmin F, Zhang L, Zasloff MA, Stewart AFR*, Chen HH*. Neuronal Protein Tyrosine Phosphatase 1B hastens Amyloid β-associated Alzheimer’s disease in mice. Journal of Neuroscience. 2020 Feb 12;40(7):1581-1593. 
(Impact Factor = 6.2).

10.Cruz SA, Qin Z, Stewart AFR, Chen HH*. Dabrafenib, an inhibitor of RIP3 kinase-dependent necroptosis, reduces ischemic brain injury. Neural Regeneration Research. 2018 doi: 10.4103/1673-5374.226394.
(Impact Factor = 5.13; Cited 19 times in 2019; Top 10 highly cited papers of the Journal)

11. Hari A, Cruz SA, Qin Z, Couture P, Vilmundarson RO, Huang H, Stewart AFR, Chen HH*. IRF2BP2-deficient microglia block the anxiolytic effect of enhanced postnatal care. Scientific Reports. 2017, doi: 10.1038/s41598-017-10349-3
(Impact Factor = 4.8)

12. Cruz SA, Hari A, Qin Z, Couture P, Huang H, Lagace DC, Stewart AFR, Chen HH*. Loss of IRF2BP2 in Microglia Increases Inflammation and Functional Deficits after Focal Ischemic Brain Injury. Frontiers in Cellular Neuroscience. 2017 Jul 19;11:201.
(Impact Factor = 4.6)

13.  Almontashiri NA, Antoine A, Zhou X, Vilmundarson R, Zhang S, Hao K, Chen HH*, Stewart AFR*. 9p21.3 coronary artery disease risk variants disrupt TEAD transcription factor binding and TEAD-dependent TGFβ regulation of p16 expression in human aortic smooth muscle cells. Circulation. 2015 Nov 24;132(21):1969-78. 
(Impact Factor = 30)

#  Editorial by MacRae CA, Pollak MR. Effect size does matter: the long road to mechanistic insight from genome wide association. Circulation, 2015 Oct 20.
(Impact Factor = 30)

14.  Chen HH*, Keyhanian K, Zhou X, Vilmundarson R, Almontashiri NA, Cruz SA, Pandey NR, Yap NL, Ho T, Stewart CA, Huang H, Hari A, Geoffrion M, McPherson R, Rayner K, Stewart AFR.  IRF2BP2 in macrophages controls inflammation and susceptibility to diet-induced obesity and atherosclerosis. Circulation Research. 2015;117:671-683. 
(Impact Factor = 17.4) 
 Featured as a Cover of the issue. Circulation Research. 2015;117 (September 25).
Editorial by Zhang H, Reilly MP. IRF2BP2: A New Player at the Crossroads of Inflammation and Lipid Metabolism. Circulation Research. 2015;117:656-658.
(Impact Factor = 17.4) 

15.  Qin Z, Zhou X, Pandey NR, Vecchiarelli HA, Stewart CA, Zhang X, Lagace DC, Brunel JC, Béïque JC, Stewart AFR, Hill MN, Chen HH*.  Chronic Stress Induces Anxiety via an Amygdalar Intracellular Cascade that Impairs Endocannabinoid Signalling. Neuron. 2015  Mar 18;85(6):1319-1331.
(Impact Factor = 17.2)

Featured & Reviewed in: Krishnan N, Tonks NK. Anxious moments for the protein tyrosine phosphatase PTP1B. Trends Neurosci. 2015 Jul 9. 
(Impact Factor = 15.6)

Editorial pick of  Science SignalingHow stress causes anxiety. 2015 Mar 20, 8 (369), pp. ec68.
(Impact Factor = 6.5)     

16. Chen HH, Stewart AFR. Making sense of GWAS: Integrating genetic variation with gene expression to derive functional mechanisms underlying disease risk. Circulation. 2015 Feb 10;131(6):519-21.
(Impact Factor = 30)

17. Almontashiri NAM, Chen HH, Mailloux RJ, Tatsuta T, Teng ACT, Mahmoud AB, Ho T, Stewart NAS, Rippstein P, Harper ME, Roberts R, Christina Willenborg6 and Jeanette Erdmann6 for the CARDIoGRAM, consortium, Pastore A, McBride H, Langer T, Stewart AFR. SPG7 variant escapes phosphorylation-regulated processing by AFG3L2, elevates mitochondrial ROS and associates with multiple clinical phenotypes. Cell Reports. (2014) 7(3):834-47. 
(Impact Factor = 9.4)

18. Zaman T, Zhou X, Pandey NR, Qin Z, Keyhanian K, Wen K, Courtney R, Stewart AFR, Chen HH*. LMO4 is essential for paraventricular hypothalamic neuronal activity and calcium channel expression to prevent hyperphagia. Journal of Neuroscience. 34(1):140-8 (2014). 
(Impact Factor = 7.9)

19. Pandey NR, Zhou X, Qin Z, Zaman T, Gomez-Smith M, Kayhanin K, Anisman H, Brunel JM , Stewart AFR, Chen HH*. LMO4 is a metabolic responsive inhibitor of PTP1B that controls hypothalamic leptin signaling. Journal of Neuroscience. 33(31):12647-55 (2013). 
(Impact Factor = 7.9)

20. Qin Z, Zhou X, Gomez-Smith M, Pandey NR, Lee KF, Lagace DC, Béïque J-C, Chen HH*. LMO4 regulates calcium-induced calcium release and synaptic plasticity in the hippocampus. Journal of Neuroscience32(12):4271-83 (2012).
(Impact Factor = 7.9)

Diseases, conditions and populations of interest

Research and clinical approaches