Prof. Brodie's Lab
Prof. Chaya Brodie is a Professor in the Mina and Everard Goodman Faculty of Life Sciences and a member of the Nano Medicine Center at the Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA).
Research in Brodie’s lab centers on cell signaling and tumorigenesis, with a focus on CNS neoplasm and the DAG/PMA receptor superfamily, as well as novel signaling pathways in the self-renewal and differentiation of neural stem cells and cancer stem cells.
Brodie and her team also study the cross talk of Protein kinase C (PKC) with tyrosine kinases and its role in the regulation of cell apoptosis and autophagy, as well as the identification of new therapeutic targets and the development of novel approaches for the imaging and treatment of brain tumors using nanoparticles and mesenchymal stem cells.
Brodie and her group are studying the molecular mechanisms underlying the development of brain tumors by exploring signal transduction pathways involved in glial cell transformation and identification of novel proteins and genes expressed in brain tumors.
One of the projects in the lab focuses on PKC, a family of phospholipid-dependent serine-threonine kinases that plays an important role in signal transduction and in the regulation of cell growth, differentiation and apoptosis. Brodie and her team focus on the role of specific PKC isoforms in the function of glial and neuronal cells, and on the interaction of PKC with tyrosine kinases. Using different PKC chimeras and PKC mutants, her group aims to identify specific domains in PKC that are involved in the different functions of specific isoforms. Based on their results, PKC has been implicated as a possible therapeutic target in malignant brain tumors (gliomas).
Another important project focuses on a novel protein, RTVP-1, that was identified downstream of PKC and which plays a major role in the regulation of the migration and invasion of gliomas cells and gliomas stem cells. The team is currently using different animal models of glioma to examine the role of PKC isoforms and RTVP-1 in the generation and maintenance of these tumors, in their infiltration and resistance to radio- and chemotherapy.
Adults Stem Cells in Cell Therapy for Neurodegenerative Disorders and Cancer
Adult mesenchymal stem cells (MSCs) are stem cells that can be easily obtained from various sources such as bone-marrow, adipose tissue and placenta. Recent reports have demonstrated that in addition to the ability of MSCs to differentiate to bone marrow stroma, blood vessels, fat, bone and cartilage, these cells also have the potential to differentiate into functional neural cells. Moreover, MSCs have been shown to exert therapeutic effects in a variety of neurological diseases and dysfunctions in experimental animal models and more recently in pilot clinical trials. Therefore, the use of MSC-derived neural cells has a great potential as an easily accessible source of autologous cells for neuronal protection, repair and cell replacement therapy in various neurodegenerative disorders.
Brodie and her team have recently developed novel approaches for the differentiation of MSCs into various neural cells. These cells are currently being examined for therapeutic benefit in models of Parkinson's disease, multiple sclerosis and spinal cord injury. In a related project, the group is investigating the role of mesenchymal stem cells in the development and functions of brain tumors and their use as a vehicle for anti-cancer treatments.
Brodie and her team research the bi-directional interaction between the nervous and immune systems and the role of this interaction in the function of neuronal and glial cells during physiological and pathological conditions. Such interaction is mediated by neurotrophins, neurotransmitters and cytokines, which modify diverse immunological and neurological parameters.
Brodie and her group are currently studying the roles of various neurotrophins and their receptors in inflammatory processes in the CNS, in the survival of neurons and glial cells, and in the pathogenesis of multiple sclerosis.
Nanotechnology and Materials
In collaboration with Prof. Shlomo Margel, an expert in the fabrication of nanoparticles for medical use, Brodie and her team created a coating that enabled the “loading” of nanoparticles with a cancer-killing peptide. Their work resulted in a compound that targets glioma cells in a process that can be followed by MRI.
Unlike chemotherapy, which involves delivering poisonous compounds to cancerous tissues, the nanoparticles developed by Brodie and Margel trigger a genetic program within the cancer cells that leads to cell death. Their work led to the launch of a new start-up company called “Nano Thera” that may give hope to gliomas patients.
Looking to the Future
Future studies in the lab aim at using cancer stem cells for the development of new brain tumor animal models that can recapitulate the drug resistance and infiltrative nature of the parental tumors, as well as the development of novel approaches for the tracking and imaging of tumor cells, stem cells and their interactions in vivo.
In addition, much of the research in the lab focuses on delineating the molecular mechanisms that are involved in the generation and transformation of glial tumors and in the neural differentiation of mesenchymal stem cells. Ongoing research is currently being performed in the development of additional therapeutic approaches for primary and metastatic brain tumors using nanoparticles and MSCs and animal models of neurodegenerative disorders are being studied to analyze the therapeutic effects of MSCs.