|1999.9 - 2003.7 B.Sc., Biology, Department of Intensive Institution, Nanjing University (Advisor: Dr. Genxi Li, Professor and Chair, Biochemistry)|
2003.9 - 2009.7 Ph.D., Department of Biochemistry, Rutgers University-University of Medicine and Dentistry of New Jersey (Advisor: Dr. Céline Gélinas, Professor and Associate Dean)
2009.9 - 2017.2 Postdoctoral Fellow, Cold Spring Harbor Laboratory (Advisor: Dr. Nicholas K. Tonks, Professor and Deputy Director, FRS)
2017.2 – now Assistant Professor, PI, School of Life Science and Technology, ShanghaiTech University
|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.
1. Gaofeng Fan. FER mediated HGF-independent regulation of HGFR/MET activates RAC1-PAK1 pathway to potentiate metastasis in ovarian cancer. Small GTPase (2017) Nov 3:1-5
2. Siwei Zhang, Gaofeng Fan, Yuan Hao, Molly Hammell, John Erby Wilkinson, Nicholas K Tonks. Suppression of protein tyrosine phosphatase N23 predisposes to breast tumorigenesis via activation of FYN kinase. Genes & Development (2017) 31(19):1939-1957 – Selected as “Cover story”
3. Wanjing Shang*, Fei Wang*, Gaofeng Fan#, Haopeng Wang#. Key elements for designing and performing a CRISPR/Cas9-based genetic screen. Journal of Genetics and Genomics (2017) 44(9):439-449. (# co-corresponding author )
4. Prajwal Gurung*, Gaofeng Fan*, John R. Lukens, Peter Vogel, Nicholas K. Tonks and Thirumala-Devi Kanneganti. Tyrosine Kinase SYK licenses MyD88 Adaptor Protein to Instigate IL-1a-Mediated Inflammatory Disease. Immunity (2017) 46(4), 635-648 (*co-first author)
5. Gaofeng Fan, Siwei Zhang, Yan Gao, Peter A. Greer and and Nicholas K. Tonks. HGF-independent Regulation of MET and GAB1 by Non-Receptor Tyrosine Kinase FER Potentiates Metastasis in Ovarian Cancer. Genes & Development(2016)30 (13), 1542-1557
6. Gaofeng Fan*, Saadat Aleem*, Ming Yang, W. Todd Miller and Nicholas K. Tonks. Protein Tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and BRK. Journal of Biological Chemistry(2015) 288 (34), 24923-24934 - Selected as “Paper of the week”
7. Gaofeng Fan*, Kazimierz O. Wrzeszczynski*, Cexiong Fu, Gang Su, Scott R. Powers, Darryl J. Pappin, Robert Lucito and Nicholas K. Tonks. A quantitative proteomics-based signature of platinum sensitivity in ovarian cancer cell lines. Biochemical Journal(2015) 465(3):433-42
8. Gaofeng Fan, Guang Lin, Robert Lucito and Nicholas K. Tonks. 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): 24923-34 - Selected as “Paper of the week”
9. Gaofeng Fan*, Matthew J. Simmons*, Sheng Ge, Jui Dutta-Simmons, Jérôme F. Kucharczak, Yacov Ron, David Weissmann, Chiann-Chyi Chen, Chandreyee Mukherjee, Eileen White and Céline Gélinas. Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma.Blood (2010) 115(17):3559-69 - Recommended by “Faculty of 1000”
10. Gaofeng Fan, Yongjun Fan, Nupur Gupta, Isao Matsuura, Fang Liu, Xiao zhen Zhou, Kun Ping Luand Céline Gélinas. The Peptidyl-Prolyl Isomerase PIN1 markedly enhances the oncogenic activity of the Rel protein subunits of NF-kB. Cancer Research(2009) 69(11): 4589-97
11. Jui Dutta, Gaofeng Fan and Céline Gélinas. CAPERa is a novel Rel-TAD-interacting factor that inhibits lymphocyte transformation by the potent Rel/NF-kB oncoprotein v-Rel. Journal of Virology(2008) 82(21): 10792-802
12. Nupur Gupta, Jeffrey Delrow, Amar Drawid, Anirvan M. Sengupta, Gaofeng Fan and Céline Gélinas. 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): 808-14
13. Younjun Fan*, Jui Dutta*, Nupur Gupta*, Gaofeng Fan* and Céline Gélinas. Regulation of programmed cell death by NF-kB and its role in tumorigenesis and therapy. Review. Adv Exp Med Biol(2008) 615:223-50(*co-first author)
14. Matthew J. Simmons, Gaofen Fan, Weixin Zong, Kurt Degenhardt, Eileen White and Céline Gélinas. Bfl-1/A1 functions, similar to Mcl-1, as a selective tBid and Bak antagonist. Oncogene(2008) 27(10): 1421-8
15. Jui Dutta*, Yongjun Fan*, Nupur Gupta*, Gaofeng Fan* and Céline Gélinas. Current insights into the regulation of programmed cell death by NF-kB. Review. Oncogene (2006) 25(51): 6800-16 (*co-first author)
16. Xinjian Liu, Yinxi Huang, Wenjun Zhang, Gaofeng Fan, Chunhai Fan and Genxi Li. Electrochemical investigation of redox thermodynamics of immobilized myoglobin: ionic and ligation effects.Langmuir(2005) 21(1): 375-8