Gaofeng FanAssistant Professor , PhD, Assistant Professor
School of Life Science and Technology
- 1999/09-2003/07, Biology, Department of Intensive Institution, Nanjing University (Advisor: Dr. Genxi Li, Professor and Chair, Biochemistry), B.Sc
- 2003/09-2009/07, Department of Biochemistry, Rutgers University-University of Medicine and Dentistry of New Jersey (Advisor: Dr. Céline Gélinas, Professor and Associate Dean), Ph.D.
- 2009/09-2017/02, Cold Spring Harbor Laboratory (Advisor: Dr. Nicholas K. Tonks, Professor and Deputy Director, FRS), Postdoctoral Fellow
- 2017/02-Present, School of Life Science and Technology, ShanghaiTech University, Assistant Professor (TENURE-TRACK)
Ovarian Cancer Metastasis and Therapeutic Resistance/Tyrosine Phosphorylation/Poly-ADP Ribosylation
Ovarian cancer is the leading cause of death from gynecological malignancies and ranks fifth of all cancer-related deaths in women. To date, there is no reliable screening test for the early detection of this“silent”killer disease, and less than 35% of women are diagnosed before Stage III, with five-year survival for Stage III or IV being less than 25%. Improvement in treatment is an urgent need for this devastating disease.
Despite recent advances in surgery, the overall survival from ovarian cancer has not improved significantly for last four decades. Failure in early detection results in disease progression to an advanced stage with metastasis. It has been shown that approximately 70% of patients presents with disease that has spread beyond the ovaries. It is almost impossible to render patients free of disease with surgery due to this diffuse feature. Therefore, our efforts to pinpoint the molecular basis for ovarian carcinoma dissemination and metastasis hold great promise to provide information that will lead to development of next generation chemotherapeutical drugs that can effectively inhibit these events after surgery.
Another major impediment to successful treatment of ovarian cancer is acquired resistance to therapy. Platinum-based chemotherapeutics combined with Taxol is the conventional treatment for ovarian cancer after surgery. However, no matter how meticulously designed the chemotherapy regimen it is, relapse remains almost inevitable in patients with advanced disease. With the improvement of our understanding of the pathological features of this heterogeneous disease, the concept of targeted therapy has led to a series of pre-clinical and clinical trails, including targeting VEGF, EGF and PDGF signaling, separately or in combination, PARP inhibition in BRCA-deficient context, and inactivation of downstream pathway PI3K-AKT. Encouraging results have been reported, especially for anti-angiogenic and anti-PARP therapies; however, acquired resistance significantly lowers treatment efficacy and still remains as the primary issue to be addressed.
My lab will integrate both biochemical and biological approaches to address these two urgent issues in ovarian cancer treatment. We will also apply high-throughput screen to identify leading compound(s) against novel and druggable target(s) revealed from our studies.
Representative Publications (*First Author, # Corresponding Author)
- 1. Zhang, Yanchun*; Xiong, Xuexue; Zhu, Qi; Zhang, Jiali; Chen, Shengmiao; Wang, Yuetong; Cao, Jian; Chen, Li; Hou, Linjun; Zhao, Xi; Hao, Piliang; Chen, Jian; Zhuang, Min; Li, Dake#; Fan, Gaofeng#.FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer cells.ELIFE. 12 May 2022. 11.
- 2. Chu, Liping*; Qu, Yuxiu; An, Yang; Hou, Linjun; Li, Juewan; Li, Weijia; Fan, Gaofeng; Song, Bao-Liang; Li, En; Zhang, Liye; Qi, Wei#.Induction of senescence-associated secretory phenotype underlies the therapeutic efficacy of PRC2 inhibition in cancer.CELL DEATH & DISEASE. 15 Feb 2022. 13(2).
- 3. Wang, Yuetong*; Wang, Fei*; Wang, Lihua*; Qiu, Shizhen*; Yao, Yufeng; Yan, Chenxu; Xiong, Xuexue; Chen, Xuyong; Ji, Quanquan; Cao, Jian; Gao, Ganglong; Li, Dake; Zhang, Liye; Guo, Zhiqian; Wang, Ruoning; Wang, Haopeng#; Fan, Gaofeng#.NAD(+) supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells.CELL REPORTS. 2021. 36(6).
- 4. Wu, Ruohan*; Chen, Xuyong; Kang, Siwen; Wang, Tingting; Gnanaprakasam, Jn Rashida; Yao, Yufeng; Liu, Lingling; Fan, Gaofeng; Burns, Mark R.; Wang, Ruoning#.De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function.SCIENCE ADVANCES. Dec 2020. 6(51).
- 5. Li, Wentao*; Qiu, Shizhen; Chen, Jian; Jiang, Shutan; Chen, Wendong; Jiang, Jingwei; Wang, Fei; Si, Wen; Shu, Yilai; Wei, Ping; Fan, Gaofeng; Tian, Ruijun; Wu, Haitao#; Xu, Chenqi#; Wang, Haopeng#.Chimeric Antigen Receptor Designed to Prevent Ubiquitination and Downregulation Showed Durable Antitumor Efficacy.IMMUNITY. 18 Aug 2020. 53(2):456-+.
- 6. Chen, Shengmiao*; Yao, Yufeng*; Zhang, Yanchun*; Fan, Gaofeng#.CRISPR system: Discovery, development and off-target detection.CELLULAR SIGNALLING. Jun 2020. 70.
- 7. Wang, Yuetong*; Cao, Jian; Liu, Weiwei; Zhang, Jiali; Wang, Zuo; Zhang, Yiqun; Hou, Linjun; Chen, Shengmiao; Hao, Piliang; Zhang, Liye; Zhuang, Min; Yu, Yang; Li, Dake; Fan, Gaofeng#.Protein tyrosine phosphatase receptor type R (PTPRR) antagonizes the Wnt signaling pathway in ovarian cancer by dephosphorylating and inactivating βcatenin.JOURNAL OF BIOLOGICAL CHEMISTRY. Nov 2019. 294(48):18306-18323.
- 8. Zhang, Jiali*; Wang, Zuo; Zhang, Siwei; Chen, Yanxun; Xiong, Xuexue; Li, Xiaojuan; Tonks, Nicholas K.#; Fan, Gaofeng#.Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER.CELLULAR SIGNALLING. Oct 2018. 50:100-110.
- 9. Yao, Xiang-Ping*; Cheng, Xuewen; Wang, Chong; Zhao, Miao; Guo, Xin-Xin; Su, Hui-Zhen; Lai, Lu-Lu; Zou, Xiao-Huan; Chen, Xue-Jiao; Zhao, Yuying; Dong, En-Lin; Lu, Ying-Qian; Wu, Shuang; Li, Xiaojuan; Fan, Gaofeng; Yu, Hongjie; Xu, Jianfeng; Wang, Ning#; Xiong, Zhi-Qi#; Chen, Wan-Jin#.Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification.NEURON. 27 Jun 2018. 98(6):1116-+.
- 10. Zhang, Siwei*; Fan, Gaofeng; Hao, Yuan; Hammell, Molly; Wilkinson, John Erby; Tonks, Nicholas K.#.Suppression of protein tyrosine phosphatase N23 predisposes to breast tumorigenesis via activation of FYN kinase.GENES & DEVELOPMENT. Oct 2017. 31(19):1939-1957.
- 11. Shang, Wanjing*; Wang, Fei*; Fan, Gaofeng#; Wang, Haopeng#.Key elements for designing and performing a CRISPR/Cas9-based genetic screen.JOURNAL OF GENETICS AND GENOMICS. 20 Sep 2017. 44(9):439-449.
- 12. Gurung, Prajwal*; Fan, Gaofeng; Lukens, John R.; Vogel, Peter; Tonks, Nicholas K.; Kanneganti, Thirumala-Devi#.Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1 alpha-Mediated Inflammatory Disease.IMMUNITY. 2017. 46(4):635-648.
- 13. Fan, Gaofeng*; Zhang, Siwei; Gao, Yan; Greer, Peter A.; Tonks, Nicholas K.#.HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer.GENES & DEVELOPMENT. 2016. 30(13):1542-1557.
- 14. Fan, Gaofeng*; Wrzeszczynski, Kazimierz O.; Fu, Cexiong; Su, Gang; Pappin, Darryl J.; Lucito, Robert; Tonks, Nicholas K.#.A quantitative proteomics-based signature of platinum sensitivity in ovarian cancer cell lines.BIOCHEMICAL JOURNAL. 2015. 465:433-442.
- 15. Fan, Gaofeng*; Aleem, Saadat; Yang, Ming; Miller, W. Todd#; Tonks, Nicholas K.#.Protein-tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and Breast Tumor Kinase.JOURNAL OF BIOLOGICAL CHEMISTRY. 2015. 290(26):15934-15947.
- 16. Fan, Gaofeng*; Lin, Guang; Lucito, Robert; Tonks, Nicholas K.#.Protein-tyrosine Phosphatase 1B Antagonized Signaling by Insulin-like Growth Factor-1 Receptor and Kinase BRK/PTK6 in Ovarian Cancer Cells.JOURNAL OF BIOLOGICAL CHEMISTRY. 2013. 288(34):24923-24934.
- 17. Fan, Gaofeng*; Simmons, Matthew J.; Ge, Sheng; Dutta-Simmons, Jui; Kucharczak, Jerome; Ron, Yacov; Weissmann, David; Chen, Chiann-Chyi; Mukherjee, Chandreyee; White, Eileen; Gelinas, Celine#.Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma.BLOOD. 2010. 115(17):3559-3569.
- 18. Fan, Gaofeng*; Fan, Yongjun; Gupta, Nupur; Matsuura, Isao; Liu, Fang; Zhou, Xiao Zhen; Lu, Kun Ping; Gelinas, Celine#.Peptidyl-Prolyl Isomerase Pin1 Markedly Enhances the Oncogenic Activity of the Rel Proteins in the Nuclear Factor-kappa B Family.CANCER RESEARCH. 2009. 69(11):4589-4597.
- 19. Dutta, Jui*; Fan, Gaofeng; Gelinas, Celine#.CAPER alpha Is a Novel Rel-TAD-Interacting Factor That Inhibits Lymphocyte Transformation by the Potent Rel/NF-kappa B Oncoprotein v-Rel.JOURNAL OF VIROLOGY. 2008. 82(21):10792-10802.
- 20. Gupta, Nupur*; Delrow, Jeffrey; Drawid, Amar; Sengupta, Anirvan M.; Fan, Gaofeng; Gelinas, Celine#.Repression of B-cell linker (BLNK) and B-cell adaptor for phosphoinositide 3-kinase (BCAP) is important for lymphocyte transformation by Rel proteins.CANCER RESEARCH. 2008. 68(3):808-814.
- 21. Fan, Yongjun*; Dutta, Jui; Gupta, Nupur; Fan, Gaofeng; Gelinas, Celine#.Regulation of programmed cell death by NF-kappa B and its role in tumorigenesis and therapy.ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY. 2008. 615:223-250.
- 22. Simmons, M. J.*; Fan, G.; Zong, W-X; Degenhardt, K.; White, E.; Gelinas, C.#.Bfl-1/A1 functions, similar to Mcl-1, as a selective tBid and Bak antagonist.ONCOGENE. 2008. 27(10):1421-1428.
- 23. Dutta, J.*; Fan, Y.; Gupta, N.; Fan, G.; Gelinas, C.#.Current insights into the regulation of programmed cell death by NF-kappa B.ONCOGENE. 2006. 25(51):6800-6816.
- 24. Liu, XJ*; Huang, YX; Zhang, WJ; Fan, GF; Fan, CH; Li, GX#.Electrochemical investigation of redox thermodynamics of immobilized myoglobin: Ionic and ligation effects.LANGMUIR. 2005. 21(1):375-378.