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Title

 

University ID

6241

ShowOnHomePage

Yes

Full Name

 

First Name

Li

Last Name

Jia

Degree

 

Faculty Keyword

cancer genomics, epigenomics, functional genomics, transcriptional regulation, hormone receptor

Office Phone

314-362-6968

Lab Phone

 

Other Phone

 

Fax

314-362-8844

Lab Address

McDonnell Sciences 750

Email

 

Research Abstract

1. Non-coding genetic variants in cancer development and progression. The human genome can be divided into two main sections, the coding (2%) and non-coding (98%) portions. Research has shown that non-coding DNA is very important in regulating whether genes are on or off, or codes for RNA other than mRNA. The evidence from the ENCODE project and other studies further indicate that a variety of regulatory elements exist in non-coding sequences, such as promoters, enhancers, silencers, and insulators. It is believed that a significant fraction of disease-causing genetic variants in humans are localized within regulatory DNA. Altering sequences in non-coding DNA tends to be equally deleterious as altering coding regions. Genome-wide association studies have uncovered a large number of disease susceptibility regions that do not overlap protein-coding genes but rather map to non-coding intervals. The sequencing of cancer genome has further revealed that the majority of somatic mutations are located in non-coding regions. Our laboratory employs a combination of Next-Gen Sequencing and biochemical approaches to understand the gene regulation code in cancer. The goal of our research is to discover functional non-coding mutations in the cancer genome and understand how they direct pathological expression of genes in cancer development and progression.
 
2. Androgen receptor directed gene expression program in prostate cancer progression. Prostate cancer growth is initially dependent on androgens through activation of the androgen receptor (AR), a ligand-dependent transcription factor. As a consequence, androgen deprivation therapy has been the cornerstone of treatment for advanced prostate cancer since 1941. Despite initial response and durable remission, an incurable castration-resistant state inevitably occurs. While novel therapies have been developed, improvements in survival are measured in months. How prostate cancer cells acquire the ability to survive and proliferate after androgen deprivation therapy remains to be determined. However, the failure of androgen deprivation therapy is not accompanied by the loss of AR or AR activity, but rather with restored AR activation through a variety of mechanisms. The goal of our research is to characterize distinct AR signaling pathways in androgen-dependent prostate cancer and castration-resistant prostate cancer identify novel AR target genes responsible for prostate cancer progression and develop new therapeutic strategies.

Middle Initial

 

Public Name

Li Jia

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Campus Box

8220

Website Url

http://pharmacogenomics.dom.wustl.edu/

Ten Word Res Desc

Gene Regulation in Cancer

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Date Last Updated

11/10/2011 10:43 AM

Publications

Ahmadiyeh N, Pomerantz MM, Grisanzio C, Herman P, Jia L, Almendro V, He HH, Brown M, Liu XS, Davis M, Caswell JL, Beckwith CA, Hills A, Macconaill L, Coetzee GA, Regan MM, Freedman ML. 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. Proc Natl Acad Sci U S A 2010 25;107(21):9742-6.
 
Jia L, Landan G, Pomerantz M, Jaschek R, Herman P, Reich D, Yan C, Kantoff P, Oh W, Manak J, Berman BP, Henderson BE, Frenkel B, Haiman CA, Freedman M, Tanay A, Coetzee GA. Functional enhancers at the gene-poor 8q24 cancer-linked locus. PLoS Genetics 2009 5(8):e1000597.
 
Pomerantz M, Ahmadiyeh N, Jia L, Herman P, Verzi M, Beckwith C, Chan J, Haiman CA, Yan C, Henderson B, Frenkel B, Barretina J, Bass A, Tabernero J, Baselga J, Shivdasani R, Coetzee G, Freeedman M. The 8q24 cancer risk variant rs6983267 demonstrates long- range interaction with MYC in colorectal cancer. Nature Genetics 2009 41(8):882-884.
 
Jia L. Berman B, Jariwala U, Cogan JP, Walters A, Yan X, Chen T, Hengen PN, Buchanan G, Frenkel B, Coetzee GA. Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, collaborators and transcriptional capacity. PLoS ONE 2008 3(11):e3645.
 
Jia L, Shen HC, Wantroba M, Khalid O, Liang G, Wang Q, Gentzschein E, Pinski JK, Stancyk FZ, Jones PA, Coetzee GA. Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cells. Molecular and Cellular Biology 2006 26(19): 7331-7341.

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Approval Status Approved
 

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Created at 11/10/2011 10:43 AM by DBBS_SP_SAPP
Last modified at 11/10/2011 12:12 PM by Kathryn Ruzicka