Position Title

Professor
Basic Science

Office Location

Hudson-Webber Cancer Research Center, Rm. 824
Mailing Address:
Karmanos Cancer Institute
4100 John R.
Mail Code: HW08AO
Detroit, MI 48201

Office Phone

313-576-8349

Office Fax

313-576-8029

Education Training

Education
(1995-1998)  Ph.D., Genetics, Fudan University, Shanghai, P.R. China
(1992-1995)  M.S. Genetics, Nanjing Railway Medical College, Nanjing, Jiangsu Province, P.R. China
(1983-1986)  B.S. Biology, Huizhou Normal College, Anhui Province, P.R.China

Postgraduate Training
(2001-2006)  Postdoctoral Research Fellow, the Johns Hopkins University
(1998-2001)  Postdoctoral Research Fellow, Mayo Clinic

Professional Experience

Faculty Appointments

(2024-Present)  Professor, Molecular Therapeutics Program, Karmanos Cancer Institute and Department of Oncology, Wayne State University School of Medicine, Detroit, MI
(2014-2024)  Associate Professor, Molecular Therapeutics Program, Karmanos Cancer Institute and Department of Oncology, Wayne State University School of Medicine, Detroit, MI
(2006-2014)  Assistant Professor, Molecular Therapeutics Program, Karmanos Cancer Institute and Department of Oncology, Wayne State University School of Medicine, Detroit, MI

Hospital or Other Professional Appointments
(2006-Present)  Member, Karmanos Cancer Institute

Major Professional Societies

American Association for Cancer Research (AACR)
American Society of Human Genetics (ASHG)

 

Honors and Awards

(1998) C.C.Tan Jiuyuan Scholarship, (National scholarship in Bioengineering, named by the American foreign academic member C.C.Tan), Fudan University, Shanghai, P.R.China
(1997)  Outstanding Research Presentation, Research tribune of Ph.D students, Fudan University, Shanghai, P.R.China
(1997)  Dong's orient scholarship, (First class scholarship Top 5 in the graduate School) Fudan University, Shanghai, P.R.China
(1996)  Dong's orient scholarship, (First class scholarship Top 5 in the graduate school) Fudan University, Shanghai, P.R.China

Courses taught

1. CB 7700 Cancer Biology Journal Club
2. CB 7210: Fundamentals of Cancer Biology
3. CB 7220: Molecular Biology of Cancer Development
4. CB 7240: Priciples of Cancer Therapy
5. CB 7300 Special Topics in Cancer Biology
6. CB 7460: Mechanisms of Neoplasia - Alterations to Cellular Signaling
7. MGG 7010: Molecular Biology and Genetics
8. PSL 6300: Biotechnology - Techniques and Applications
9. F30/F31 Grant writing course

Research Interests

My laboratory is focusing on deciphering the molecular mechanisms involved in human breast cancer initiation, progression and metastasis, as well as chemoresistance. Based on the mechanisms identified, we will then develop novel therapeutic strategies to overcome these clinical challenges with an eventual goal of curing malignant breast cancer.

Two major projects are currently ongoing in the laboratory.
1. Transcriptional regulation of novel metastasis driving genes in TNBC. Using global profiling technologies, including genomics, proteomics and metabolomics, we identify new molecular signatures in EMT program and cancer stem cells. We are now investigating the functional roles of the EMT promoting transcription factors in breast cancer metastasis and chemoresistance using integrative genetic, epigenetic approach as well as animal models and clinical specimens. We are specifically interested in discovering novel molecular mechanisms of transcriptional regulation of these EMT driving genes. These mechanisms include recruiting epigenetic modulators for transcriptional activation and interaction with spliceosome to facilitate RNA splicing.

2. Molecular characterization of metastasis driving proteins in metabolic reprogramming in TNBC cells. There is increasing evidence that mitochondrial dysfunction and metabolic reprogramming are closely associated with modulation of cell cycle and cell differentiation, which promotes cancer progression to a metastatic phenotype. However, there have been few studies linking pro-metastatic genes to impaired mitochondrial function and metabolic reprogramming. We demonstrate that a novel metastasis driving protein EGFL9 can not only regulates cMET signaling pathway, but also translocates to the mitochondria and drives a metabolic switch from oxidative phosphorylation to glycolysis. We are now clarifying this protein in TNBC and studying the detailed mechanism of EGFL9 in regulating metabolism in TNBC cells using LC-MS/MS based targeted metabolomics. The effect of these metabolites regulated by EGFL9 on cancer cells or tumor microenvironment will be further analyzed.

Publications

1.    Mitchell AV., Wu L., Block CJ., Zhang M., Hackett J., Craig DB., Chen W., Zhao Y., Zhang B., Dang Y., Zhang X., Zhang S., Wang C., Gibson H., Pile LA., Kidder B., Matherly L., Yang Z, Dou Y., Wu G.. FOXQ1 Recruits the MLL Complex to Activate Transcription of the EMT Program and Promote Breast Cancer Metastasis. Nat. Commun. 2022; 13, 6548.

2.   Mitchell AV., Wu J., Meng F., Dong L., Block CJ., Song WM., Zhang B., Jing Li, Wu G.. DDR2 coordinates EMT and metabolic reprogramming as a shared effector of FOXQ1 and SNAI1. Cancer Res. Commun.. 11/2022;2(11):1388-1403. 

3.   Block CJ֗֗, Mitchell AV, Wu L, Glassbrook J, Craig D, Chen W, Dyson G, DeGracia D, Polin L, Ratnam M, Gibson H, Wu G.. RNA binding protein RBMS3 is a common EMT effector that modulates triple-negative breast cancer progression via stabilizing PRRX1 mRNA. Oncogene. 2021;40(46):6430-6442. 

4.  Block CJ, Dyson G, Campeanu IJ, Watza D, Ratnam M, Wu G. A stroma-corrected ZEB1 transcriptional signature is inversely associated with antitumor immune activity in breast cancer. Sci Rep. 2019; 9(1):17807.

5.   Meng F, Wu L, Dong L, Mitchell AV, Block CJ, Liu J, Zhang H, Lu Q, Song WM, Zhang B, Chen W, Hu J, Wang J, Yang Q, Hüttemann M, Wu G. EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming. Nat Commun. 2019 Nov 6;10(1):5033. 

6.   Wu L, Meng F, Dong L, Block CJ, Mitchell AV*, Wu J, Jang H, Chen W, Polin L, Yang Q, Dou QP, Wu G. Disulfiram and BKM120 in Combination with Chemotherapy Impede Tumor Progression and Delay Tumor Recurrence in Tumor Initiating Cell-Rich TNBC. Sci Rep. 2019; 9(1):236.

 7. Meng F., Speyer CL., Zhang B., Zhao Y., Chen W., Gorski DH., Miller FR., Wu G.. PDGFRα and β Play Critical Roles in Mediating Foxq1-Driven Breast Cancer Stemness and Chemoresistance. Cancer Res., 2015; 75(3):584-93.                

8.  Zhang H, Meng F, Wu S., Kreike B., Chen W., Sethi S., Miller FR, and Wu G..  Engagement of I-branching β-1, 6-N-acetylglucosaminyltransferase GCNT2 in Breast Cancer Metastasis and Transforming Growth Factor-β Signaling. Cancer Res., Cancer Res. 2011; 71(14):4846-56.                       

9.  Zhang H, Meng F, Liu G, Zhang B, Zhu J, Wu F, Ethier SP, Miller F, and Wu G.. Forkhead Transcription Factor Foxq1 Promotes Epithelial-Mesenchymal Transition and Breast Cancer Metastasis. Cancer Res. 2011, 71(4):1292-301. 

10.  Zhang H., Chen D., Ringler J, Chen W, Cui Q, Ethier SP, Dou QP., Wu G.. Disulfiram Treatment Facilitates PI3K Inhibition in Human Breast Cancer Cells In Vitro and In Vivo. Cancer Res, 2010, 70(10):3996-4004. 

 

 

Faculty Status

Basic Science

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