Jianfang Ning, PhD

Assistant Professor, Department of Neurosurgery

Jianfang Ning

Contact Info

Assistant Professor, Department of Neurosurgery


Fellowship in Neurosurgery Research, Massachusetts General Hospital, Boston

PhD, Microbiology, Wuhan University, China

BSc, Biological science, Central China Normal University, China

Summary

Dr. Ning received her undergraduate degree in biological science from Central China Normal University, her PhD in microbiology from China’s Wuhan University, and completed a fellowship in neurosurgical research at Massachusetts General Hospital in Boston. She is a member of the editorial board of the Journal of Neurology and Experimental Neural Science.

Dr. Ning has made several presentations at professional association meetings and is the first or contributing author of numerous peer-reviewed articles published in professional journals. As a member of the Brain Tumor Research Center of Massachusetts General Hospital team, Dr. Ning contributed to discoveries that could potentially lead to more effective treatments for brain tumor patients. 

Professional Associations

American Association for Cancer Research

Research

Research Summary/Interests

“My research goal is to develop novel therapeutic approaches for cancer by using virotherapy (oncolytic virus, OV), molecular-targeted therapeutics and chemotherapy through targeting DNA damage responses (DDR) in cancer cells and the immune system. For postdoc training, I joined the lab of the Brain Tumor Research Center (BTRC) at Massachusetts General Hospital supervised by Robert Martuza, MD, and Samuel David Rabkin, PhD, who have been developing oncolytic herpes simplex virus (oHSV) therapies for cancer with a particular emphasis on brain tumors, represented by glioblastoma, a fatal brain tumor with median survival of 15 months. Cancer stem cell is one of the primary reasons causing the poor diagnosis. I have had an opportunity to use a panel of patient-derived glioblastoma stem cells (GSCs) as a lab resource that recapitulate the characteristics of patient tumors and generate orthotopic mouse models for therapeutic testing.

“In 2013, my colleagues and I found that an oHSV armed with an immunomodulatory cytokine, interleukin 12, significantly inhibited the growth of murine GSC-generated intracerebral tumors in syngeneic mice. The survival benefit resulted from not only direct oHSV oncolysis of GSCs, but also increased IFN-Y release, inhibition of angiogenesis and reduction of the number of regulatory T cells in the tumor. This work demonstrated multifaceted oncolytic virus therapy for glioblastoma-targeting tumor cells, tumor microenvironment and the immune system.

“My major research interest is to explore DDR in cancer to gain selective therapeutic effects. I led the recently published study that combined oHSV and poly(ADP-ribose) polymerase inhibitor (PARPi) for the treatment of GSCs. I found the combination treatment synergistically killed GSCs, irrespective of their PARPi sensitivity, and significantly increased DNA damage and apoptosis in vitro and in vivo. The synergy is caused by oHSV manipulation of DDR by degrading the key homologous recombination repair (HR) protein Rad51 and inhibiting HR. This was the first report of PARPi + oHSV combination therapy in cancer stem cells. OHSV antagonism of DDR provides a novel strategy for combination therapy with drugs inhibiting DDR pathways, like PARPi, in GBM and other tumors. This work establishes oHSV as a unique PARPi partner to overcome the current clinical limitations of PARPi such as resistance. To further expand the use of PARPi in cancers, I screened a variety of DDR targeting agents in combination with PARPi. I discovered that ATR inhibitor sensitized GSCs to PARPi and the combination therapy prolonged survival of mice bearing brain tumors derived from PARPi-sensitive and -resistant GSCs. Furthermore, my investigation identified the specific mechanisms that underlie the cancer-selective cytotoxicity of this approach and new biomarkers for PARPi-response in cancer cells.”

Publications

Peer-reviewed publications

  1. Ning J, Wakimoto H, Peters C, Martuza RL, and Rabkin SR. Rad51 Degradation: Role in Oncolytic Virus-Poly(ADP-Ribose) Polymerase Inhibitor Combination Therapy in Glioblastoma. J Natl Cancer Inst. 2017 Mar 1;109(3):1-13.
  2. Cheema TA, Wakimoto H, Fecci PE, Ning J, Kuroda T, Jeyaretna DS, Martuza RL, Rabkin SD. Multifaceted oncolytic virus therapy for glioblastoma in an immunocompetent cancer stem cell model. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12006-11.
  3. Meng MX, Ning JF, Yu JY, Chen DD, Meng XL, Xu JP, Zhang J. Antitumor activity of recombinant antimicrobial peptide penaeidin-2 against kidney cancer cells. J Huazhong Univ Sci Technolog Med Sci. 2014 Aug;34(4):529-34
  4. Zhang Y, Ning JF*, Qu XQ, Meng XL, Xu JP. TAT-mediated oral subunit vaccine against white spot syndrome virus in crayfish. J Virol Methods. 2012 Apr;181(1):59-67.
  5. Ning JF, Zhu W, Xu JP, Zheng CY, Meng XL. Oral delivery of DNA vaccine encoding VP28 against white spot syndrome virus in crayfish by attenuated Salmonella typhimurium. Vaccine. 2009, 27:1127-1135.

*Co-first author

Other peer-reviewed publications (reviews and editorials):

  1. Ning J, Wakimoto H. Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy. Front. Microbiol. 2014 Jun 20;5:303
  2. Ning J, Wakimoto H, Rabkin SD. Immunovirotherapy for glioblastoma. Cell Cycle. 2014 Jan 15;13(2):175-6.
  3. Cheema TA, Fecci PE, Ning J, Rabkin SD. Immunovirotherapy for the treatment of glioblastoma. Oncoimmunology. 2014 Jan 1;3(1): e27218
  4. Ning J, Rabkin SD. Current Status of Gene Therapy for Brain Tumors. Brain tumor gene therapy. Gene therapy chapter. 2014

Oral Presentations

  1. Targeting DNA damage responses for glioblastoma therapy with oncolytic herpes simplex virus and molecularly targeted therapeutics, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China, 2015
  2. Targeting DNA damage responses for glioblastoma therapy with oncolytic herpes simplex virus and PARP inhibitor, Wuhan University, China, 2017
  3. Targeting DNA damage responses with PARP inhibitor and oncolytic herpes simplex virus (oHSV) for glioblastoma, Cambridge Healthtech Institute’s Immuno-Oncology Summit, Boston, 2017

Abstracts, Poster Presentations and Exhibits Presented at Professional Meetings

  1. Poster: Targeting Glioblastoma Stem Cells with Oncolytic HSV and PARP Inhibitors, American Society of Gene & Cell Therapy (ASGCT) 17th Annual Meeting Washington D.C., 2014
  2. Poster: Targeting Glioblastoma Stem Cells with Oncolytic HSV and PARP Inhibitors, American Association for Cancer Research (AACR) Annual Meeting, 2-15, Philadelphia, PA
  3. Oral presentation: Targeting DNA damage responses for glioblastoma therapy with oncolytic herpes simplex virus and molecularly targeted therapeutics, 9th International Oncolytic Virus Therapeutics Conference, Boston, MA, 2015
  4. Poster: ATR inhibitors synergize with PARP inhibitors in killing glioblastoma stem cells and treating glioblastoma, AACR Annual Meeting, Washington, DC, 2017