Marc Symons, PhD

Investigator, Karches Center for Oncology Research, The Feinstein Institute for Medical Research

Co-Director, Brain Tumor Biotech Center, The Feinstein Institute for Medical Research

Director, Light Microscopy Facility, The Feinstein Institute for Medical Research

Professor, Molecular Medicine & Neurosurgery, Hofstra Northwell School of Medicine

Phone: (516) 562-1193

About the Investigator

Dr. Symons obtained a PhD in biophysics in 1980 from the Brussels Free University, Belgium. After postdoctoral training at the Weizmann Institute, Israel, and the University of California at San Francisco, he started his independent career at Onyx Pharmaceuticals, a startup biotech company in the Bay Area, where he discovered the roles of the Rho family GTPases Rac1, Cdc42 and RhoA in cancer development.

Research Focus

Upon moving back to the academic environment, first at the Picower Institute and subsequently at what is now called The Feinstein Institute for Medical Research, Dr. Symons has focused his research on the molecular mechanisms that are responsible for tumor cell invasion and survival. A major focus of the research is on two malignant brain tumors, glioblastoma and medulloblastoma.

Targeting tumor-associated macrophages in brain and other cancers

Tumor-associated macrophages (TAMs) have been known to play a major role in tumor cell invasion and metastasis for over a decade now. Accumulating date indicate that this role extends to most, if not all cancers. More recently, TAMs also have been implicated in tumor cell survival and immune suppression. TAMs are attracted by tumors and in turn secrete factors that promote tumor cell survival, growth and invasion. The Symons lab is trying to identify these factors and also studies the mechanisms by which tumor cells coerce TAMs into secreting factors that promote the malignant behavior of the tumor cells, with the goal of identifying novel therapeutic interventions.

Glioblastoma-associated macrophages are largely made up of microglia, the resident macrophages in the brain. In a search for drugs that deactivate TAMs, the group found that the anti-inflammatory drug semapimod blocks microglia-stimulated glioblastoma cell invasion and diminishes the protective effect of macrophages to radiation therapy, resulting in significant radio-sensitization of glioblastoma tumors in a mouse model of the disease. Subsequently, semapimod was also shown to be a potent inhibitor of metastasis in mouse models of Ewing’s sarcoma and breast cancer. Further development of semapimod as novel therapy for cancer is in progress.

An additional project in the laboratory is the identification of other macrophage-modulating drugs. To this end, a high throughput assay has been established to identify inhibitors of macrophage-induced tumor cell survival. Screening of this assay with a library of clinically approved drugs is underway.

Radiosensitization of medulloblastoma tumors

Significant progress has been made in the treatment of medulloblastoma patients over the past several decades. Unfortunately however, current therapies, in particular radiotherapy, have significant long-term side-effects in children. Therefore, there is a great need for new therapeutic strategies. Radio-sensitization, the combination of radiotherapy with rationally designed drugs that target proteins that promote radio-resistance, can achieve therapeutic benefit with lower doses of radiation. This approach is expected to diminish the side-effects of radiotherapy and to enhance the quality of life of the patient. Dr. Ruggieri in the group has identified several medulloblastoma radio-resistance genes using RNA interference.

One of these is MRK, a protein kinase that is activated by radiation therapy. In collaboration with Dr. Yousef Al-Abed, Head, Center for Molecular Innovation, the team has designed a specific inhibitor of MRK, termed M443, and showed that M443 strongly radio-sensitizes medulloblastoma cells, but not normal brain cells. Most drugs, including M443, very poorly penetrate into brain tumor tissue and current efforts in the laboratory therefore are now geared toward developing methods to deliver M443 to the brain. The team also plans to extend the use of M443 as a radio-sensitizer to other cancers, in particular to head and neck tumors, for which radiation is mainstay therapy, but also causes severe side effects.

Lab Members



Maria Ruggieri
Assistant Investigator

Amanda Chan
Assistant Investigator
Manager Light Microscopy Facility

Yukie Takabatake
Post-doctoral Research Trainee

Yumi Fujisawa
Research Associate

Carter Somerville*
Hofstra Graduate Student

Caroline Maloney**
Elmezzi Scholar

Babar Khan
Elmezzi Scholar

Yao Liu
Elmezzi Scholar

Avery Wright
Pediatric Hem-Onc Fellow

*Carter Somerville is jointly mentored by Dr. Valentin Pavlov and Dr. Marc Symons
**Caroline Maloney is jointly mentored by Dr. Bettie Steinberg and Dr. Marc Symons


Universitaire Instelling Antwerpen, Belgium
Degree: Licentiaat Physics

Vrije Universiteit Brussel, Belgium
Degree: PhD

  1. Qiu R-G, Chen J, Kirn D, McCormick F and Symons M. “An essential role for Rac in Ras transformation.” 1995, Nature 374, 457-9.
  2. Symons M, Derry JMJ, Karlak B, Jiang S, McCormick F, Francke U and Abo A. “Wiskott-Aldrich Syndrome Protein, a novel effector for the GTPase Cdc42Hs, is implicated in actin polymerization.” 1996, Cell 84, 723-34.
  3. Chuang Y, Tran NL, Rusk N, Nakada N, Berens ME and Symons M. “Role of synaptojanin 2 in glioma cell migration and invasion.” 2004, Cancer Res 64, 8271-75.
  4. Chan AY, Coniglio SJ, Chuang YY, Michaelson D, Knaus UG, Philips MR and Symons M. “Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion.” 2005, Oncogene 24, 7821-9.
  5. Chuang Y-Y, Valster A and Symons M. “The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration.” 2007, J Cell Sci, 120: 1927-34.
  6. Coniglio SJ, Zavarella S and Symons M. “Pak1 and Pak2 mediate tumor cell invasion through distinct signaling mechanisms.” 2008, Mol Cell Biol, 28: 4162-72.
  7. Zavarella S, Nakada M, Belverud S, Coniglio SJ, Chan A, Mittler, MA, Schneider SJ and Symons M. “Role of Rac1-regulated signaling in medulloblastoma invasion.” 2009, J Neurosurgery Pediatrics 4: 97-104.
  8. Coniglio SJ, Dobrenis K, Stanley ER, Symons M and Segall J. “Microglial-stimulation of glioma invasion involves EGFR and CSF-1R signaling.” 2012. Molecular Medicine, 18: 519-27.
  9. Vanan I, Dong Z, Tosti E, Warshaw G, Symons M and Ruggieri R. “Role of a DNA damage checkpoint pathway in ionizing radiation-induced glioblastoma cell migration and invasion.” 2012. Cell Mol Neurobiol, 32: 1199-208.
  10. Kwiatkowska A, Didier S, Fortin SP, Chuang YY, White T, Berens ME, Rushing E, Eschbacher J, Tran NL, Chan A and Symons M. “Role of the small GTPase RhoG in glioblastoma cell invasion.” 2012. Molecular Cancer , 11:65 doi:10.1186/1476-4598-11-65.
  11. Korkina O, Dong Z, Marullo A, Warshaw G, Symons M, Ruggieri R. “The MLK-related kinase (MRK) is a novel RhoC effector that mediates lysophosphatidic acid (LPA)-stimulated tumor cell invasion.” 2013. J Biol Chem. 288: 5364-73.
  12. Miller IS, Didier SM, Murray DW, Turner TH, Issaivanan M, Ruggieri R, Al-Abed Y and Symons M. 2014. “Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia.” PLoS One 9(5):e95885.
  13. Hesketh AJ, Maloney C, Behr CA, Edelman M, Glick RD, Al-Abed Y, Symons M, Soffer SZ and Steinberg BM. 2015. “The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation.” PLoS One 10(12):e0145197.
  14. Markowitz D, Powell C, Tran NL, Berens ME, Ryken TC, Vanan M, Rosen L, He M, Sun S, Symons M, Al-Abed Y and Ruggieri R (2016) “Pharmacological inhibition of the protein kinase MRK/ZAK radiosensitizes medulloblastoma.” Mol Can Ther, May 20. pii: molcanther.0849.2015.

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