"The support of The Sontag Foundation is really critical in helping us to reach our goal of making real progress in the treatment of patients with glioblastoma. Transcription factor networks are emerging as attractive diagnostics and therapeutic targets for this disease yet our understanding of these networks is just beginning. This grant really does ensure that we can set our sights high and move our research into exciting areas of transcriptional biology that otherwise would not be possible at this early stage in my career."
- Dr. Keith Ligon
- Chief of Neuropathology, Brigham and Women's Hospital
- Director, DFCI Center for Patient Derived Models
- Co-PI, NCI Human Cancer Models Initiative (HCMI) Cancer Models Derivation Center at the Broad/DFCI
- Associate Member, Broad Institute
- Associate Professor, Harvard Medical School
- Associate Pathologist and Neuropathologist, Pathology, Brigham And Women's Hospital/Consultant, Pathology, Boston Children's Hospital
About DSA-Funded Research
Recent studies have suggested that malignant gliomas may contain a confusing mixture of differentiated cells and stem cells, and that the stem cells are most important for the growth of the tumor and its inability to be treated. The transcription factor (TF) protein SOX2 acts as a master regulator of stem cell biology in embryonic and neural stem cells but whether it plays a role in cancer stem cells is not known. We have recently identified SOX2 as a defining marker of gliomas and in some patients SOX2 is amplified at the genomic level implying it may play a role in tumor growth. The goals of this proposal are to define the function and targets of SOX2 activity in normal CNS stem cells and glioma stem cells. To accomplish this, we will first test SOX2 function in stem cell regions of the brain using genetically engineered Cre-loxP mouse models of gliomas. Secondly, we will create a TF interaction map to comprehensively define what genes SOX2 controls in neural stem cells and gliomas using novel ChIP-Seq techniques. Lastly, we will define the parts of the SOX2 protein that are required for its function in human glioma stem cells. Through these studies we will gain novel insights into the importance of SOX2 in normal stem cells, gliomas, and other cancers that express SOX2. Furthermore, the roadmap of SOX2 function that these studies will provide should help to guide rational development of new targeted therapeutics effective against cancer stem cells in glioma patients.
"I cannot think of a more forward thinking neuropathologist working in the brain tumor field. Given his current trajectory, I am confident Keith will become a leader in the field of neuroscience and neuropathology."
David Rowitch, M.D., Ph.D.
University of California, San Francisco
"Keith is extremely bright, driven by a love for science, honest and collaborative. In my view, he represents the prototype of a physician scientist and one of the best I have ever seen."
Massimo Loda, M.D.
Harvard Medical School