Qianben Wang

Overview:

My laboratory is primarily interested in understanding the epigenetic mechanisms driving progression of hormone-dependent cancers. We focus on studying how transcription factor-centered, multi-layer transcription regulatory networks drive hormone-dependent cancers, which involve transcription factors (e.g. nuclear hormone receptors, FOXA1, and GATA2), transcription coactivators (e.g. Mediator and histone acetyltransferases), and epigenetic regulators (e.g. histone modifications, chromatin looping and nucleosome positioning).

Positions:

Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2002

University of Maryland, Baltimore

Postdoctoral Fellow/Instructor in Molecular and Cellular Oncology, Dana Farber Cancer Institute

Harvard Medical School

Grants:

Systems Analysis of Epigenomic Architecture in Cancer Progression (Project 2: Fine-scale nucleosome repositioning of enhancers for hormone-independent genomic function)

Administered By
Pathology
Role
Principal Investigator
Start Date
End Date

Role of oncogenic phosphorylated MED1 in aggressive prostate cancer

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Novel genomic mechanism for ligand-dependent transcription by androgen receptor

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Novel Tumor Suppressive Role of Phosphodiesterases in Prostate Cancer

Administered By
Pathology
Awarded By
Ohio State University
Role
Principal Investigator
Start Date
End Date

Population/single-cell profiling of chromatin accessibility for hormone-dependent cancers

Administered By
Pathology
Awarded By
University of Texas Health Science Center at San Antonio
Role
Principal Investigator
Start Date
End Date

Publications:

Transcription recycling assays identify PAF1 as a driver for RNA Pol II recycling.

RNA Polymerase II (Pol II) transcriptional recycling is a mechanism for which the required factors and contributions to overall gene expression levels are poorly understood. We describe an in vitro methodology facilitating unbiased identification of putative RNA Pol II transcriptional recycling factors and quantitative measurement of transcriptional output from recycled transcriptional components. Proof-of-principle experiments identified PAF1 complex components among recycling factors and detected defective transcriptional output from Pol II recycling following PAF1 depletion. Dynamic ChIP-seq confirmed PAF1 silencing triggered defective Pol II recycling in human cells. Prostate tumors exhibited enhanced transcriptional recycling, which was attenuated by antibody-based PAF1 depletion. These findings identify Pol II recycling as a potential target in cancer and demonstrate the applicability of in vitro and cellular transcription assays to characterize Pol II recycling in other disease states.
Authors
Chen, Z; Hankey, W; Zhao, Y; Groth, J; Huang, F; Wang, H; Campos, AR; Huang, J; Roeder, RG; Wang, Q
MLA Citation
Chen, Zhong, et al. “Transcription recycling assays identify PAF1 as a driver for RNA Pol II recycling.Nat Commun, vol. 12, no. 1, Nov. 2021, p. 6318. Pubmed, doi:10.1038/s41467-021-26604-1.
URI
https://scholars.duke.edu/individual/pub1500357
PMID
34732721
Source
pubmed
Published In
Nature Communications
Volume
12
Published Date
Start Page
6318
DOI
10.1038/s41467-021-26604-1

Dietary omega-3 fatty acid intake impacts peripheral blood DNA methylation -anti-inflammatory effects and individual variability in a pilot study.

Omega-3 or n-3 polyunsaturated fatty acids (PUFAs) are widely studied for health benefits that may relate to anti-inflammatory activity. However, mechanisms mediating an anti-inflammatory response to n-3 PUFA intake are not fully understood. Of interest is the emerging role of fatty acids to impact DNA methylation (DNAm) and thereby modulate mediating inflammatory processes. In this pilot study, we investigated the impact of n-3 PUFA intake on DNAm in inflammation-related signaling pathways in peripheral blood mononuclear cells (PBMCs) of women at high risk of breast cancer. PBMCs of women at high risk of breast cancer (n=10) were obtained at baseline and after 6 months of n-3 PUFA (5 g/d EPA+DHA dose arm) intake in a previously reported dose finding trial. DNA methylation of PBMCs was assayed by reduced representation bisulfite sequencing (RRBS) to obtain genome-wide methylation profiles at the single nucleotide level. We examined the impact of n-3 PUFA on genome-wide DNAm and focused upon a set of candidate genes associated with inflammation signaling pathways and breast cancer. We identified 24,842 differentially methylated CpGs (DMCs) in gene promoters of 5507 genes showing significant enrichment for hypermethylation in both the candidate gene and genome-wide analyses. Pathway analysis identified significantly hypermethylated signaling networks after n-3 PUFA treatment, such as the Toll-like Receptor inflammatory pathway. The DNAm pattern in individuals and the response to n-3 PUFA intake are heterogeneous. PBMC DNAm profiling suggests a mechanism whereby n-3 PUFAs may impact inflammatory cascades associated with disease processes including carcinogenesis.
Authors
Frankhouser, DE; Steck, S; Sovic, MG; Belury, MA; Wang, Q; Clinton, SK; Bundschuh, R; Yan, PS; Yee, LD
MLA Citation
Frankhouser, David E., et al. “Dietary omega-3 fatty acid intake impacts peripheral blood DNA methylation -anti-inflammatory effects and individual variability in a pilot study.J Nutr Biochem, vol. 99, Aug. 2021, p. 108839. Pubmed, doi:10.1016/j.jnutbio.2021.108839.
URI
https://scholars.duke.edu/individual/pub1494311
PMID
34411715
Source
pubmed
Published In
J Nutr Biochem
Volume
99
Published Date
Start Page
108839
DOI
10.1016/j.jnutbio.2021.108839

The oncogenomic function of androgen receptor in esophageal squamous cell carcinoma is directed by GATA3.

Authors
Huang, F; Chen, H; Zhu, X; Gong, T; Li, X; Hankey, W; Wang, H; Chen, Z; Wang, Q; Liu, Z
MLA Citation
Huang, Furong, et al. “The oncogenomic function of androgen receptor in esophageal squamous cell carcinoma is directed by GATA3.Cell Res, vol. 31, no. 3, Mar. 2021, pp. 362–65. Pubmed, doi:10.1038/s41422-020-00428-y.
URI
https://scholars.duke.edu/individual/pub1463922
PMID
33139924
Source
pubmed
Published In
Cell Res
Volume
31
Published Date
Start Page
362
End Page
365
DOI
10.1038/s41422-020-00428-y

A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer.

Cellular metabolism in cancer is significantly altered to support the uncontrolled tumor growth. How metabolic alterations contribute to hormonal therapy resistance and disease progression in prostate cancer (PCa) remains poorly understood. Here we report a glutaminase isoform switch mechanism that mediates the initial therapeutic effect but eventual failure of hormonal therapy of PCa. Androgen deprivation therapy inhibits the expression of kidney-type glutaminase (KGA), a splicing isoform of glutaminase 1 (GLS1) up-regulated by androgen receptor (AR), to achieve therapeutic effect by suppressing glutaminolysis. Eventually the tumor cells switch to the expression of glutaminase C (GAC), an androgen-independent GLS1 isoform with more potent enzymatic activity, under the androgen-deprived condition. This switch leads to increased glutamine utilization, hyperproliferation, and aggressive behavior of tumor cells. Pharmacological inhibition or RNA interference of GAC shows better treatment effect for castration-resistant PCa than for hormone-sensitive PCa in vitro and in vivo. In summary, we have identified a metabolic function of AR action in PCa and discovered that the GLS1 isoform switch is one of the key mechanisms in therapeutic resistance and disease progression.
Authors
Xu, L; Yin, Y; Li, Y; Chen, X; Chang, Y; Zhang, H; Liu, J; Beasley, J; McCaw, P; Zhang, H; Young, S; Groth, J; Wang, Q; Locasale, JW; Gao, X; Tang, DG; Dong, X; He, Y; George, D; Hu, H; Huang, J
MLA Citation
Xu, Lingfan, et al. “A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer.Proc Natl Acad Sci U S A, vol. 118, no. 13, Mar. 2021. Pubmed, doi:10.1073/pnas.2012748118.
URI
https://scholars.duke.edu/individual/pub1447414
PMID
33753479
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
118
Published Date
DOI
10.1073/pnas.2012748118

Alternative polyadenylation of mRNA and its role in cancer.

Alternative polyadenylation (APA) is a molecular process that generates diversity at the 3' end of RNA polymerase II transcripts from over 60% of human genes. APA is derived from the existence of multiple polyadenylation signals (PAS) within the same transcript, and results in the differential inclusion of sequence information at the 3' end. While APA can occur between two PASs allowing for generation of transcripts with distinct coding potential from a single gene, most APA occurs within the untranslated region (3'UTR) and changes the length and content of these non-coding sequences. APA within the 3'UTR can have tremendous impact on its regulatory potential of the mRNA through a variety of mechanisms, and indeed this layer of gene expression regulation has profound impact on processes vital to cell growth and development. Recent studies have particularly highlighted the importance of APA dysregulation in cancer onset and progression. Here, we review the current knowledge of APA and its impacts on mRNA stability, translation, localization and protein localization. We also discuss the implications of APA dysregulation in cancer research and therapy.
Authors
Yuan, F; Hankey, W; Wagner, EJ; Li, W; Wang, Q
MLA Citation
Yuan, Fuwen, et al. “Alternative polyadenylation of mRNA and its role in cancer.Genes Dis, vol. 8, no. 1, Jan. 2021, pp. 61–72. Pubmed, doi:10.1016/j.gendis.2019.10.011.
URI
https://scholars.duke.edu/individual/pub1423340
PMID
33569514
Source
pubmed
Published In
Genes and Diseases
Volume
8
Published Date
Start Page
61
End Page
72
DOI
10.1016/j.gendis.2019.10.011