Professor, The 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, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
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 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.
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.
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.
Manager Light Microscopy Facility
Hofstra Graduate Student
Pediatric Hem-Onc Fellow
Universitaire Instelling Antwerpen, Belgium
Degree: Licentiaat Physics
Vrije Universiteit Brussel, Belgium