Ming Chen

Overview:

Our laboratory is interested in understanding the molecular and genetic events underlying cancer progression and metastasis. The focus of our work is a series of genetically engineered mouse models that faithfully recapitulate human disease. Using a combination of mouse genetics, omics technologies, cross-species analyses and in vitro approaches, we aim to identify cancer cell–intrinsic and –extrinsic mechanisms driving metastatic cancer progression, with a long–term goal of developing new therapeutic strategies for preventing and treating metastatic disease. 

Positions:

Assistant Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2009

University of Rochester

Research Fellow in Medicine and Pathology, Beth Israel Deaconness Medical Center

Harvard Medical School

Grants:

De Novo Lipogenesis and Chemosensitivity of Prostate Cancer

Administered By
Pathology
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Exploiting ferroptosis for the treatment of lethal neuroendocrine prostate cancer

Administered By
Pathology
Awarded By
Mike Slive Foundation
Role
Principal Investigator
Start Date
End Date

Publications:

ROLES OF VITAMIN E IN PROSTATE AND PROSTATE CANCER

Authors
Yeh, S; Ni, J; Chang, E; Yin, Y; Chen, M
MLA Citation
Yeh, Shuyuan, et al. “ROLES OF VITAMIN E IN PROSTATE AND PROSTATE CANCER.” Prostate Cancer, WORLD SCIENTIFIC, 2005, pp. 263–76. Crossref, doi:10.1142/9789812569202_0011.
URI
https://scholars.duke.edu/individual/pub1430974
Source
crossref
Published Date
Start Page
263
End Page
276
DOI
10.1142/9789812569202_0011

Abi1 loss drives prostate tumorigenesis through activation of EMT and noncanonical WNT signaling.

<jats:p> 280 </jats:p><jats:p> Background: Prostate cancer is characterized by heterogeneity of mechanisms which are poorly understood but pointing to epithelial plasticity as the key mechanism in progression to metastatic disease. ABI1, a member of WAVE complex and actin cytoskeleton regulator and adaptor protein, is proposed to act as tumor suppressor in prostate cancer, but the mechanism of tumor progression due to Abi1 loss is not clear. Methods: To address Abi1’s role in prostate cancer we used CRISPR-based gene editing and retroviral expression to manipulate Abi1 levels in prostate cancer cell lines. Levels of Abi1 expression in prostate organoid tumor cell lines were evaluated by Western blotting and/or RNA sequencing. Association of Abi1 loss with tumor grade was evaluated by immunohistochemistry. Results: Abi1 expression is downregulated in tumor organoid cell lines from metastatic bone and lymph node biopsies. Moreover, low Abi1 expression is associated with high-grade prostate tumors (GG3 or higher, p &lt; 0.001). Disruption of Abi1 gene in a benign prostate epithelial cell line RWPE-1 resulted in a gain of invasive phenotype, which is characterized by loss of cell-cell adhesion markers and increased migratory ability of RWPE-1 Abi1 KO spheroids. Through RNA sequencing and protein expression analysis we discovered that Abi1 loss leads to activation of non-canonical WNT signaling and EMT pathways, which are rescued by re-expression of Abi1. Furthermore, increase in STAT3 phosphorylation upon Abi1 inactivation and evidence for high affinity interaction of FYN-SH2 domain with Abi1 pY421 support the model that Abi1 acts as a gatekeeper of the non-canonical WNT-EMT pathway activation downstream from FZD2 receptor. The gene expression profile of Abi1-EMT-WNT pathway overlaps with the reported gene signature of high-risk prostate tumors. Conclusions: Abi1 contributes to prostate cancer progression and epithelial plasticity through regulation of EMT-WNT pathways. Understanding of Abi1’s role may provide more mechanistic understanding of prostate cancer tumor progression. </jats:p>
Authors
Nath, D; Li, X; Mondragon, C; Post, D; Chen, M; Hryniewicz-Jankowska, A; Caza, T; White, J; Kuznetsov, V; Hehnly, H; Khanna, R; Gleicher, S; Jamaspishvili, T; Berman, DM; Zhang, F; Kung, SHY; Fazli, L; Bratslavsky, G; Pandolfi, PP; Kotula, L
MLA Citation
Nath, Disharee, et al. “Abi1 loss drives prostate tumorigenesis through activation of EMT and noncanonical WNT signaling.Journal of Clinical Oncology, vol. 37, no. 7_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 280–280. Crossref, doi:10.1200/jco.2019.37.7_suppl.280.
URI
https://scholars.duke.edu/individual/pub1417001
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
280
End Page
280
DOI
10.1200/jco.2019.37.7_suppl.280

The expanded role of fatty acid metabolism in cancer: new aspects and targets.

Cancer cells undergo metabolic reprogramming to support cell proliferation, growth, and dissemination. Alterations in lipid metabolism, and specifically the uptake and synthesis of fatty acids (FAs), comprise one well-documented aspect of this reprogramming. Recent studies have revealed an expanded range of roles played by FA in promoting the aggressiveness of cancer while simultaneously identifying new potential targets for cancer therapy. This article provides a brief review of these advances in our understanding of FA metabolism in cancer, highlighting both recent discoveries and the inherent challenges caused by the metabolic plasticity of cancer cells in targeting lipid metabolism for cancer therapy.
Authors
MLA Citation
Chen, Ming, and Jiaoti Huang. “The expanded role of fatty acid metabolism in cancer: new aspects and targets.Precis Clin Med, vol. 2, no. 3, Sept. 2019, pp. 183–91. Pubmed, doi:10.1093/pcmedi/pbz017.
URI
https://scholars.duke.edu/individual/pub1414854
PMID
31598388
Source
pubmed
Published In
Precis Clin Med
Volume
2
Published Date
Start Page
183
End Page
191
DOI
10.1093/pcmedi/pbz017

Abi1 loss drives prostate tumorigenesis through activation of EMT and non-canonical WNT signaling.

BACKGROUND: Prostate cancer development involves various mechanisms, which are poorly understood but pointing to epithelial mesenchymal transition (EMT) as the key mechanism in progression to metastatic disease. ABI1, a member of WAVE complex and actin cytoskeleton regulator and adaptor protein, acts as tumor suppressor in prostate cancer but the role of ABI1 in EMT is not clear. METHODS: To investigate the molecular mechanism by which loss of ABI1 contributes to tumor progression, we disrupted the ABI1 gene in the benign prostate epithelial RWPE-1 cell line and determined its phenotype. Levels of ABI1 expression in prostate organoid tumor cell lines was evaluated by Western blotting and RNA sequencing. ABI1 expression and its association with prostate tumor grade was evaluated in a TMA cohort of 505 patients and metastatic cell lines. RESULTS: Low ABI1 expression is associated with biochemical recurrence, metastasis and death (p = 0.038). Moreover, ABI1 expression was significantly decreased in Gleason pattern 5 vs. pattern 4 (p = 0.0025) and 3 (p = 0.0012), indicating an association between low ABI1 expression and highly invasive prostate tumors. Disruption of ABI1 gene in RWPE-1 cell line resulted in gain of an invasive phenotype, which was characterized by a loss of cell-cell adhesion markers and increased migratory ability of RWPE-1 spheroids. Through RNA sequencing and protein expression analysis, we discovered that ABI1 loss leads to activation of non-canonical WNT signaling and EMT pathways, which are rescued by re-expression of ABI1. Furthermore, an increase in STAT3 phosphorylation upon ABI1 inactivation and the evidence of a high-affinity interaction between the FYN SH2 domain and ABI1 pY421 support a model in which ABI1 acts as a gatekeeper of non-canonical WNT-EMT pathway activation downstream of the FZD2 receptor. CONCLUSIONS: ABI1 controls prostate tumor progression and epithelial plasticity through regulation of EMT-WNT pathway. Here we discovered that ABI1 inhibits EMT through suppressing FYN-STAT3 activation downstream from non-canonical WNT signaling thus providing a novel mechanism of prostate tumor suppression.
Authors
Nath, D; Li, X; Mondragon, C; Post, D; Chen, M; White, JR; Hryniewicz-Jankowska, A; Caza, T; Kuznetsov, VA; Hehnly, H; Jamaspishvili, T; Berman, DM; Zhang, F; Kung, SHY; Fazli, L; Gleave, ME; Bratslavsky, G; Pandolfi, PP; Kotula, L
MLA Citation
Nath, Disharee, et al. “Abi1 loss drives prostate tumorigenesis through activation of EMT and non-canonical WNT signaling.Cell Commun Signal, vol. 17, no. 1, Sept. 2019, p. 120. Pubmed, doi:10.1186/s12964-019-0410-y.
URI
https://scholars.duke.edu/individual/pub1411011
PMID
31530281
Source
pubmed
Published In
Cell Communication and Signaling : Ccs
Volume
17
Published Date
Start Page
120
DOI
10.1186/s12964-019-0410-y

Corrigendum: Loss of LDAH associated with prostate cancer and hearing loss.

Authors
Currall, BB; Chen, M; Sallari, RC; Cotter, M; Wong, KE; Robertson, NG; Penney, KL; Lunardi, A; Reschke, M; Hickox, AE; Yin, Y; Wong, GT; Fung, J; Brown, KK; Williamson, RE; Sinnott-Armstrong, NA; Kammin, T; Ivanov, A; Zepeda-Mendoza, CJ; Shen, J; Quade, BJ; Signoretti, S; Arnos, KS; Banks, AS; Patsopoulos, N; Liberman, MC; Kellis, M; Pandolfi, PP; Morton, CC
MLA Citation
Currall, Benjamin B., et al. “Corrigendum: Loss of LDAH associated with prostate cancer and hearing loss.Hum Mol Genet, vol. 28, no. 10, May 2019, pp. 1753–54. Pubmed, doi:10.1093/hmg/ddz036.
URI
https://scholars.duke.edu/individual/pub1402720
PMID
31222336
Source
pubmed
Published In
Hum Mol Genet
Volume
28
Published Date
Start Page
1753
End Page
1754
DOI
10.1093/hmg/ddz036

Research Areas:

Animal models
Lipids
Metabolism
Metastasis
Mitogen-Activated Protein Kinases
PTEN Phosphohydrolase
Prostate--Cancer
Tumor Suppressor Proteins