Skip Ribbon Commands
Skip to main content

DBBS

:

FacultyList: (no title)

Title

 

University ID

5857

ShowOnHomePage

Yes

Full Name

 

First Name

Shiming

Last Name

Chen

Degree

 

Faculty Keyword

Gene regulation, transcription factors, photoreceptor development, retinal degeneration, drug treatment

Office Phone

314-747-4350

Lab Phone

314-747-4351

Other Phone

 

Fax

314-747-4211

Lab Address

617 McMillan

Email

 

Research Abstract

Rod and cone photoreceptors in the retina convert light to neuronal signals. Development and maintenance of these neurons require precisely regulated expression of a set of genes (the photoreceptor transcriptome) that are critical for photoreceptor function. Over-expression or under-expression of certain of these genes can lead to developmental defects or photoreceptor degeneration. Our laboratory studies the molecular mechanisms that control this expression and the implications of these mechanisms in disease pathogenesis and treatments. Photoreceptor gene transcription is regulated by interactions between a network of transcription factors and promoter/enhancer elements on the target genes. We have focused on two of the factors, the cone-rod homeobox protein Crx and nuclear receptor Nr2e3, both of which are linked to human photoreceptor diseases, including Leber's congenital amaurosis, cone-rod dystrophy and retinitis pigmentosa.
 
We investigate the function and regulatory network associated with Crx and Nr2e3 using molecular genetics and biochemical approaches:
 
1) protein-protein interaction assays to identify and characterize their interacting partners;
 
2) transgenic mouse, cell transfection and protein-DNA binding assays to identify DNA elements and protein factors that regulate their expression;
 
3) chromatin immunoprecipitation (ChIP) assays to identify direct targets of the two proteins and their co-factors, and defects in target binding due to disease-causing mutations;
 
4) ChIP and chromosome conformation capture (3C) assays to reveal epigenetic changes, including histone modifications and intrachromosomal interactions, of rod and cone genes during retinal development and disease;
 
5) knock-out/knock-in mouse studies to investigate the mechanisms by which mutations in Crx, Nr2e3 and their associated factors cause photoreceptor degeneration;
 
6) mechanism-based therapy development using cultured cells and knock-out/knock-in mutant mice as models, including AAV-mediated gene delivery and small epigenetic modulators.
 
These studies together will greatly enhance our understanding of the cellular and molecular basis of photoreceptor degeneration diseases and provide new avenues and animal models for therapy development.

Middle Initial

 

Public Name

Shiming Chen

Doctoral Degree1

 

Doctoral Degree2

 

Primary Title

 

Secondary Title

 

Third Title

 

Fourth Title

 

Primary Department

 

Secondary Department

 

Third Department

 

Fourth Department

 

Division Primary Department

 

Campus Box

8096

Website Url

http://vr-core.wustl.edu/Pages/Chen-Lab.aspx

Ten Word Res Desc

Molecular mechanisms regulating photoreceptor transcriptome in healthy and diseased retina

Micro Category1

 

Micro Category2

 

Micro Category3

 

Plant Category

 

Comp Category

 

DBBS Faculty

 

Archived Faculy Flag

 

Date Last Updated

11/10/2011 3:07 PM

Publications

Peng G-H and Chen S.  Active opsin loci adopt intrachromosomal loops that depend on the photoreceptor transcription factor network. Proc Natl Acad Sci USA 2011 108(43):17821-17826.  PMCID:PMC3203788.
 
Onishi A, Peng G-H, Poth EM, Lee DA, Chen J, Alexis U, de Melo J, Chen S, Blackshaw S.  The orphan nuclear hormone receptor ERR{beta} controls rod photoreceptor survival. Proc Natl Acad Sci USA 2010 107(25):11579-11584.  PMCID:PMC2895124
 
Onishi A, Peng G-H, Chen S, Blackshaw S.  Pias3-dependent SUMOylation controls mammalian cone photoreceptor differentiation. Nature Neuroscience 2010 13(9):1059-1065. PMCID:PMC2932661
 
Onishi A*, Peng G-H*, Hsu C, Alexis U, Chen S#, Blackshaw S#. Pias3-Dependent SUMOylation Directs Rod Photoreceptor Development. Neuron 2009 61(2): 234-246. PMCID:PMC2701228 (Recommended reading by Faculty of 1000) *Equal-contributing first authors. #Co-corresponding authors.
 
Peng G-H and Chen S. Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation. Hum Mol Genet 2007 16(20):2433-2452. PMCID:PMC2276662 (Cover article).
 
Palhan VB, Chen S, Peng GH, Tjernberg A, Gamper AM, Fan Y, Chait BT, La Spada AR, Roeder RG. Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proc Natl Acad Sci USA 2005 102(24):8472-8477.PMCID:PMC1150862
 
Peng G-H, Ahmad O, Ahmad F. Liu J, Chen S. The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Hum Mol Genet 2005 14(6):747-764.PMID:15689355 For more publications, go to http://tiny.cc/ChenPub

Show Bio Page

Yes

Exclude Email

No

Thumbnail_Image_Url

http://dbbs.wustl.edu/Faculty Photos Thumbnail/Chen_S.jpg

Profile_Image_Url

http://dbbs.wustl.edu/Faculty Photos/Chen_S.jpg

Primary Program

 

Secondary Program

 

Teritiary Program

 

Fourth Program

 

Fifth Program

 

Research Image Description

 

Research Image Url

 

Social Media Url

 
Approval Status Approved
 

Attachments

Created at 11/10/2011 3:07 PM by DBBS_SP_SAPP
Last modified at 11/11/2011 8:59 AM by Kathryn Ruzicka