Investigator, The Feinstein Institute for Medical Research
Director, Light Microscopy Facility, The Feinstein Institute for Medical Research
Professor, Molecular Medicine & Neurosurgery, Hofstra North Shore-LIJ School of Medicine
Phone: (516) 562-1193
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.
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 dissection of signaling pathways that are responsible for tumor cell invasion and survival, with current emphasis on brain tumors.
Overview of research in the laboratory
The research focuses on two types of malignant tumors, glioblastoma and medulloblastoma. Glioblastoma is one of the most aggressive of all human cancers and currently is still an incurable disease. Medulloblastoma is the most common malignant childhood brain tumor and accounts for over 20% of all childhood brain tumors.
A protein network that is responsible for brain tumor spreading
Work in the laboratory over the past several years has revealed a large network of proteins that is critical for the spread of both glioblastoma and medulloblastoma deep into the normal brain. The core of this network is made up of members of the Rho family of small GTPases. Other constituents of this network include activators of these GTPases. Some of these activating proteins are over-expressed in glioblastoma, whereas others are over-expressed in medulloblastoma. Current efforts in the lab are geared toward providing additional evidence to validate some of these network components as novel therapeutic targets.
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 radioresistance, 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. To search for medulloblastoma radioresistance genes, Dr. Symons currently is using a powerful screening method (RNA interference).
One protein that he has identified is MRK, a protein kinase that is activated by radiotherapy. Interestingly, MRK is also part of the Rho GTPase-controlled network that is responsible for brain tumor spread. He found that interfering with MRK makes tumors more sensitive to radiation treatment. This indicates that a drug that blocks MRK activity should reduce the radiation dose necessary to kill tumor cells and diminish radiation-induced side effects. Based on these findings, he has teamed up with Dr. Al-Abed, director of medicinal chemistry at The Feinstein Institute, to develop a drug that specifically blocks MRK activity.
Targeting microglia to treat glioblastoma tumors
Dr. Symons also is studying how glioblastoma tumors use the immune system to their own advantage. The resident immune cells in the brain, called microglia, are strongly attracted by glioblastoma tumors. Once recruited, the microglia exacerbate the malignancy of the tumor. He has identified several factors that communicate between the tumor and the microglia and currently he is testing drugs that block some of these factors. He found that one of these drugs acts as a potent radiosensitizing agent, preventing tumors from growing back after radiotherapy. He plans to evaluate the efficacy of this drug in clinical trials as soon as possible.
Manager Light Microscopy Facility
Ian S Miller
Post Doc Res Fellow
Visiting Post Doc Res Fellow
Universitaire Instelling Antwerpen, Belgium
Degree: Licentiaat Physics
Vrije Universiteit Brussel, Belgium
- 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.
- 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.
- 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.
- 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.
- Chan AY, Akhtar M, Zhen, Y, Brenner, M, Gulko, PS and Symons M. “The small GTPase Rac regulates the proliferation and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients.” 2007, Mol Med, 13: 297-304.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Chuang YY, Xu X, Kwiatkowska A, Tsapraillis G, Hwang H, Petritis K, Flynn D and Symons M. “Regulation of synaptojanin 2 5’-phosphatase activity by Src.” 2012. Cell Adhesion and Migration, in press.
- Kwiatkowska A and Symons M. “Signaling determinants of glioma cell invasion.” 2013. Adv Exp Med Biol. 986: 121-41.