HSIEN-SUNG HUANG (黃憲松)ORCID Follow
|Profile 2016-03-07 13:52:00|
1.1994~1998: B.S., Pharmacy, Taipei Medical University, Taipei, Taiwan.
2.1998~2000: M.S., Biochemistry, National Taiwan University, Taipei, Taiwan.
3.2003~2008: Ph.D., Neuroscience, University of Massachusetts Medical School, Worcester, MA.
|Career and Experience||
2013- : Assistant Professor, Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
1.2000-2002: Military Instructor, Division of Health Service, Army Logistics School, Taipei, Taiwan.
2.2002-2003: Research Assistant, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
3.2008-2012: Postdoctoral Fellow, Department of Cell and Molecular Physiology, University of North Carolina, School of Medicine, Chapel Hill, NC.
|Research field||Epigenetic mechanisms in brain development and behavior.|
Research Outline 2014-10-16 15:36:08The significance of genomic imprinting for brain development and behavior
Maternally or paternally inherited genomes are not functionally equivalent due to genomic imprinting, an epigenetic process through which genes are expressed in a parent-of-origin manner. A disproportionately high number of imprinted genes are expressed in the brain, suggesting imprinting has a powerful influence on neurodevelopment. However, our understanding of genomic imprinting has remained limited. This lack of understanding is due, in part, to the complex spatiotemporal, gender-specific, species-specific, and gene isoform-specific patterning of imprinting. Dysregulation of imprinted genes causes neurological disorders such as Autism, Angelman syndrome and Prader-Willi syndrome. Furthermore, parent-of-origin effects influence the inheritance of other disorders such as schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, seizure, Tourette syndrome, and multiple sclerosis. Despite the disease relevance of genomic imprinting, the biology underlying imprinting is poorly understood and there have been no successful attempts to modify genomic imprinting for therapeutics purposes.
My recent work was the first to demonstrate a targeted small molecule approach for activating a disease-related imprinted gene. Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by deletion or mutation of the maternal allele of the ubiquitin protein ligase E3A (UBE3A). However, no effective treatment exists for AS. Notably, the paternal UBE3A allele is intact but is epigenetically silenced. This biology raises the possibility that AS could be treated by activating the paternal UBE3A allele and hence substitutes for the dysfunctional maternal allele. Using a small molecule screen, my work in mouse models found that topoisomerase inhibitors can unsilence the paternal Ube3a allele. This discovery was the first ever to demonstrate that a disease-relevant imprinted gene can be unsilenced. This work raises the possibility that AS can be treated by activating the paternal UBE3A allele, and also demonstrates that this is a viable approach for treating myriad other imprinting disorders.
My immediate research goals are to identify the molecular mechanisms by which topoisomerase inhibitors unsilence Ube3a, and to understand how this unsilencing becomes long-lasting. This research will guide the development of new AS therapeutics.? My long-term goals are to elucidate how genomic imprinting is established, maintained, readout and erased in a cell type-specific manner. This knowledge will increase our basic understanding of how genomic imprinting impacts brain development and function. I will achieve this goal by developing a comprehensive screen to identify cell type-specific imprinted genes in the mouse brain. The function of these newly identified imprinted genes will be established by taking advantage of existing mouse models and the developing new mouse models to perform gain- and loss-of-function studies. This will allow me to establish a blueprint of imprinted genes in mouse, and will provide me with a framework to determine why and how these imprinted genes exist. My research insights into genomic imprinting will deepen our understanding on brain evolution and function, and will herald a new approach for developing pharmacological therapies for epigenetic disorders.
Publications 19 2017-01-10 14:13:01
Ordered by publish date
- Analysis of Genome-Wide Monoallelic Expression Patterns in Three Major Cell Types of Mouse Visual Cortex Using Laser Capture Microdissection PLOS ONE 2016 -09 | journal-article vol.11,no.9,page.e0163663 Scopus: 0 Web of Science: 0 Impact Factor: 2.806
- Neuronal splicing regulator RBFOX3 (NeuN) regulates adult hippocampal neurogenesis and synaptogenesis PLoS ONE 2016 | journal-article vol.11,no.10 Scopus: 4 Web of Science: 4 Impact Factor: 2.806
- Wiring Specificity and Synaptic Diversity in the Mouse Lateral Central Amygdala. The Journal of neuroscience : the official journal of the Society for Neuroscience 2016 -Apr | journal-article vol.36,no.16,page.4549-63 Scopus: 2 Web of Science: 2 Impact Factor: 5.988
- RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function Scientific Reports 2015 | journal-article vol.5 Scopus: 11 Web of Science: 9 Impact Factor: 4.259
- Snx14 regulates neuronal excitability, promotes synaptic transmission, and is imprinted in the brain of mice PLoS ONE 2014 | journal-article vol.9,no.5 Scopus: 13 Web of Science: 11 Impact Factor: 2.806
- Behavioral deficits in an Angelman syndrome model: Effects of genetic background and age Behavioural Brain Research 2013 | journal-article vol.243,no.1,page.79-90 Scopus: 40 Web of Science: 40 Impact Factor: 3.002
- Topoisomerases facilitate transcription of long genes linked to autism Nature 2013 | journal-article vol.501,no.7465,page.58-62 Scopus: 121 Web of Science: 6 Impact Factor: 40.137
- Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons Nature 2012 | journal-article vol.481,no.7380,page.185-191 Scopus: 170 Web of Science: 138 Impact Factor: 40.137
- Chromatin protein L3MBTL1 is dispensable for development and tumor suppression in mice Journal of Biological Chemistry 2010 | journal-article vol.285,no.36,page.27767-27775 Scopus: 20 Web of Science: 20 Impact Factor: 4.125
- RPP25 is developmentally regulated in prefrontal cortex and expressed at decreased levels in autism spectrum disorder Autism Research 2010 | journal-article vol.3,no.4,page.153-161 Scopus: 3 Web of Science: 3 Impact Factor: 3.765
- Advances in understanding visual cortex plasticity Current Opinion in Neurobiology 2009 | journal-article vol.19,no.3,page.298-304 Scopus: 19 Web of Science: 17 Impact Factor: 6.133
- Epigenetic Regulation in Human Brain-Focus on Histone Lysine Methylation Biological Psychiatry 2009 | journal-article vol.65,no.3,page.198-203 Scopus: 139 Web of Science: 119 Impact Factor: 11.412
- Molecular Determinants of Dysregulated GABAergic Gene Expression in the Prefrontal Cortex of Subjects with Schizophrenia Biological Psychiatry 2009 | journal-article vol.65,no.12,page.1006-1014 Scopus: 139 Web of Science: 135 Impact Factor: 11.412
- A set of differentially expressed miRNAs, including miR-30a-5p, act as post-transcriptional inhibitors of BDNF in prefrontal cortex Human Molecular Genetics 2008 | journal-article vol.17,no.19,page.3030-3042 Scopus: 145 Web of Science: 143 Impact Factor: 5.34
- Isolation of neuronal chromatin from brain tissue BMC Neuroscience 2008 | journal-article vol.9 Scopus: 97 Web of Science: 83 Impact Factor: 2.312
- GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia PLoS ONE 2007 | journal-article vol.2,no.8 Scopus: 140 Web of Science: 124 Impact Factor: 2.806
- Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters Journal of Neuroscience 2007 | journal-article vol.27,no.42,page.11254-11262 Scopus: 206 Web of Science: 192 Impact Factor: 5.988
- Chromatin immunoprecipitation in postmortem brain Journal of Neuroscience Methods 2006 | journal-article vol.156,no.1-2,page.284-292 Scopus: 63 Web of Science: 59 Impact Factor: 2.554
- Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders Brain Research Reviews 2006 | journal-article vol.52,no.2,page.293-304 Scopus: 230 Web of Science: 212 Impact Factor: 2017 N/A
Projects 2 2014-10-31 11:33:02
Ordered by project period
Constructing a Three-dimensional Map of Genomic Imprinting in the Brain (建立大腦中印記基因的三維立體圖譜)Project Number : NHRI-EX103-10316NC PI : HSIEN-SUNG HUANG (黃憲松) Co-PI : Funding IC : 財團法人國家衛生研究院 Project Period : 10301~10312
Explore the Roles of RBFOX3 (Neun) in the Brain Development and Behavior (探索RBFOX3蛋白質對大腦發育及行為的影響)Project Number : NSC102-2320-B002-001 PI : HSIEN-SUNG HUANG (黃憲松) Co-PI : Funding IC : 行政院國家科學委員會 Project Period : 10204~10307