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Glioma, a common form of primary central nervous system tumors, is an aggressive, incurable type of brain tumors. This heterogeneous tumor population, is enriched in a subset of brain-tumor initiating cells or glioma stem cells (GSCs) with self-renewal and tumor initiation capacities. Our group is focused on studying the major genetic hubs driving this cancer subpopulation and the molecular aspects governing self-renewal and tumor initiation. In our studies we use a multidisciplinary approach combining targeted chemical and genetic inhibitors as well as protein profiling to interrogate GSCs and develop novel therapies for brain tumors. Using this approach, we have identified metabolic dependencies in highly aggressive GSCs which can be exploited to specifically target these cells. We are also interested in studying tumor plasticity, in particular the ability of GSCs to change their transcriptional profile in response to different environmental or therapeutic insults, thereby favoring a more aggressive and resistant tumor population. While the incidence of primary brain tumors is relatively low, about one third of all extracranial cancer patients develop brain metastases (BM), a significant cause of patient morbidity and mortality. We are also studying various mechanisms of cancer metastasis to the brain. These studies could help us understand the mechanism of cancer brain tropism in order to prevent brain metastasis and increase survival in cancer patients.
Christian E. Badr, PhDAssistant Professor of Neurology, Harvard Medical SchoolAssistant in Neuroscience, Massachusetts General Hospital
Dr. Badr received his M.Sc. in Cell Engineering from “Henri Poincare University”- France and a PhD in Molecular biology from “Vrije University” - The Netherlands. In 2010 he joined Dr. Bakhos Tannous lab at Massachusetts General Hospital as a post-doctoral Fellow. He is currently an Assistant Professor and principal investigator in the Department of Neurology at Massachusetts General Hospital and Harvard Medical School.
Arsalan Hashemiaghdam, MD
Alessandro Sammarco, PhD candidate
Past Lab Members
Aleksandar Kirov, MSc.
Major Research Projects in Our Lab
Understanding plasticity, inherent heterogeneity and “survival queues” in Gliomas
Determining different genetic drivers of Breast cancer tropism to the brain
Transcriptional profiles and genetic signatures of brain tumor cells define the major glioblastoma subtypes and can be used to guide prognosis. The mesenchymal subset for example, is generally associated with resistance to current therapies and a poor prognosis. Recent evidence indicates plasticity between GSCs subtypes where GCSs can undergo differentiation into a more aggressive subtype through intrinsic activation of various transcription factors. In a recent study, we have identified a subpopulation of glioblastoma stem cells that escape differentiation. These cells possess a stem-like signature with prominent mesenchymal features. They tend to be more aggressive when implanted into the brain of nude mice as compared to their parental GSCs line and have a superior resistance to radiation and therapy. Our findings endorse cellular plasticity and intratumor heterogeneity in glioblastoma.
We are developing different in vitro models and performing genome-scale genetic screening to identify different genes that control the GSCs fate. This work could have direct therapeutic implications by blocking the rise of aggressive GBM phenotypes or reverting the latter into a clinically-manageable tumor type.
Identifying vulnerabilities and new genetic targets: Developing targeted therapeutics
Identifying vulnerabilities and dependencies in primary cancer cells might be key to overcoming resistance and tumor recurrence in patients. Our lab is working towards the identification of new therapeutic targets that could be exploited to treat brain tumors and other cancer types.
Ubiquitin ligase complex role in GBM and breast cancer
The ubiquitin- proteasome system controls many aspects of cell regulation and homeostasis through ubiquitination and degradation of substrate proteins. Various components of the ubiquitin proteasome are dysregulated in human diseases including cancer. We have identified one such complex that plays a key role in gliomas and breast cancer. Disruption of this complex leads to cancer cell death. We are currently exploring different strategies to develop therapeutics targeting this ubiquitin ligase complex.
Targeting metabolic vulnerabilities in cancer (Reactive Oxygen Species, lipid metabolism)
Using targeted inhibitors and genetic profiling of different primary GBM tumor cells and GSCs subtypes, we noted a marked increase in different metabolic pathways and identified key enzymes responsible for maintaining tumor progression and cell proliferation. We are testing different targeted inhibitors of these key enzymes to block different metabolic pathways essential for tumor growth using in vitro as well as orthotopic brain tumor models in mice.
Exploring alternative strategies to deliver therapeutics to the brain (Intranasal delivery; gene therapy)
In an effort to improve drug delivery to brain tumors and minimize systemic toxicity, we are exploring different strategies to deliver therapeutics to the brain. We are working towards delivery strategies such as intranasal delivery with the following advantages:
Brain tumor metastasis are particularly lethal and hard to treat. Understanding the mechanism of cancer brain tropism could help prevent brain metastasis and increase survival in cancer patients. We are working on generating breast cancer brain metastasis models and using them for in vivo genetic screens to identify genes that control brain tropism of breast cancer cells.
We are continuously seeking highly motivated and talented individuals to join our research team. We welcome applicants at different levels of training/education (undergraduate, graduate and medical students, Residents and Fellows). Interested individuals should send a curriculum vitae to Dr. Christian E. Badr at firstname.lastname@example.org.
Read about and apply for residency, fellowship and observership programs at http://www.massgeneral.org/neurology/education/.
All applicants should register with the Mass General Careers Web site at http://www.massgeneral.org/careers/viewall.aspx.
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Badr LabBuilding 14913th St., Room 6.404 Charlestown, MA 02129
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