Our Research
The Ligon Lab conducts basic and translational research on adult and pediatric brain tumors. Some of our main research areas are listed below.
Genomic identification of novel oncogenic drivers of pediatric gliomas.
Pediatric gliomas are the most common solid tumor of children, yet oncogenic drivers of these tumors had not been identified until recently. Our lab led and contributed to this field by assembling some of the largest collections of well-characterized glioma tissue samples and performed comprehensive genomic studies using array CGH and next-generation sequencing to identify the drivers of these tumors. We identified BRAF(V600E) mutation in gliomas, new oncogenic transcription factors as drivers of low grade gliomas (MYBL1, MYB, and SOX2), and mutations in ACVR1 and FGFR1 signaling pathways in high grade gliomas. Our current work focuses on identification of drug targets in these cancers.
Biology of patient derived cancer models and preclinical investigation.
A major limitation to development of more effective cancer therapies is the paucity of human cancer models which accurately represent the diversity of cancer phenotypes and genotypes seen in patients. To begin to address this our lab created an enterprise-wide Living Tissue Bank and we have created more than 1000 patient models including primary cell cultures, patient derived cell lines (PDCL), and patient derived xenografts (PDX) from more than 15 different cancer types in collaboration with the Beroukhim Lab. We used 70 GBM cell lines in a 400-drug screen to identify MDM2 inhibitors as one of the most effective agents in GBM PDCL and PDX models. In breast to brain PDX models we, with the Zhao Lab, identified combined PI3K and MTOR inhibition as a highly effective therapy capable of inducing durable remissions in HER2+ PDX models. Both studies led to clinical trials in patients and we are currently working with Dr. Patrick Wen and others to analyze these studies.
The Center for Patient Derived Models, which Dr. Ligon directs, is a key collaborator in institutional model creation efforts, as well as creating and distributing models for other investigators for all cancer types. See the CPDM page to learn more.
Developing novel genomic and functional diagnostic assays for cancer.
Genomic and functional diagnostic technologies are widely used in basic research but have unique barriers to translation into clinical practice. Our lab has led research efforts to develop methods to facilitate clinical translation of these technologies in diagnostic pathology labs. With Dr. Azra Ligon, we performed research to develop novel methods for FFPE whole genome array CGH and implemented this as one of the first routine whole genome diagnostic assays for cancer. In collaborative research we developed some of the first multiplex CLIA mutation and sequencing assays (OncoMap and OncoPanel) capable of examining more than 300 cancer causing genes and mutations and translated these into routine practice. In collaboration with the Meyerson Lab, have developed novel methods for single cell genomics applied to clinical samples that can detect resistance mutations in single cancer cells. Functional diagnostics has great potential to personalize the treatment of patient tumors, but few devices have been available for such testing in a clinical setting. In collaboration with the Manalis lab at MIT we have demonstrated that drug response in single living cancer cells can be predicted using a novel microfluidic nanotechnology device, the Suspended Microchannel Resonator (SMR), to measure the change in mass of cancer cells in response to treatments.
Investigation of targeted therapies in human glioma clinical trials.
Our lab has led correlative research for several clinical trials and preclinical trials of novel targeted therapies in gliomas. Analysis of efficacy using next-gen sequencing, array CGH, immunohistochemistry, and MGMT methylation specific PCR testing. Findings of note have included identification of MGMT methylation as a marker of better prognosis in low grade gliomas of all types. In other studies we have studied the role of PI3K/AKT/mTOR and MDM2/TP53 signaling in adult GBM. These studies carried out in collaboration with NCI consortium investigators or as PI initiated trials helped to better understand the trial results and advance the field of integrated biomarker driven trial analysis.
To learn more about our research, see our recent publications.
Genomic identification of novel oncogenic drivers of pediatric gliomas.
Pediatric gliomas are the most common solid tumor of children, yet oncogenic drivers of these tumors had not been identified until recently. Our lab led and contributed to this field by assembling some of the largest collections of well-characterized glioma tissue samples and performed comprehensive genomic studies using array CGH and next-generation sequencing to identify the drivers of these tumors. We identified BRAF(V600E) mutation in gliomas, new oncogenic transcription factors as drivers of low grade gliomas (MYBL1, MYB, and SOX2), and mutations in ACVR1 and FGFR1 signaling pathways in high grade gliomas. Our current work focuses on identification of drug targets in these cancers.
Biology of patient derived cancer models and preclinical investigation.
A major limitation to development of more effective cancer therapies is the paucity of human cancer models which accurately represent the diversity of cancer phenotypes and genotypes seen in patients. To begin to address this our lab created an enterprise-wide Living Tissue Bank and we have created more than 1000 patient models including primary cell cultures, patient derived cell lines (PDCL), and patient derived xenografts (PDX) from more than 15 different cancer types in collaboration with the Beroukhim Lab. We used 70 GBM cell lines in a 400-drug screen to identify MDM2 inhibitors as one of the most effective agents in GBM PDCL and PDX models. In breast to brain PDX models we, with the Zhao Lab, identified combined PI3K and MTOR inhibition as a highly effective therapy capable of inducing durable remissions in HER2+ PDX models. Both studies led to clinical trials in patients and we are currently working with Dr. Patrick Wen and others to analyze these studies.
The Center for Patient Derived Models, which Dr. Ligon directs, is a key collaborator in institutional model creation efforts, as well as creating and distributing models for other investigators for all cancer types. See the CPDM page to learn more.
Developing novel genomic and functional diagnostic assays for cancer.
Genomic and functional diagnostic technologies are widely used in basic research but have unique barriers to translation into clinical practice. Our lab has led research efforts to develop methods to facilitate clinical translation of these technologies in diagnostic pathology labs. With Dr. Azra Ligon, we performed research to develop novel methods for FFPE whole genome array CGH and implemented this as one of the first routine whole genome diagnostic assays for cancer. In collaborative research we developed some of the first multiplex CLIA mutation and sequencing assays (OncoMap and OncoPanel) capable of examining more than 300 cancer causing genes and mutations and translated these into routine practice. In collaboration with the Meyerson Lab, have developed novel methods for single cell genomics applied to clinical samples that can detect resistance mutations in single cancer cells. Functional diagnostics has great potential to personalize the treatment of patient tumors, but few devices have been available for such testing in a clinical setting. In collaboration with the Manalis lab at MIT we have demonstrated that drug response in single living cancer cells can be predicted using a novel microfluidic nanotechnology device, the Suspended Microchannel Resonator (SMR), to measure the change in mass of cancer cells in response to treatments.
Investigation of targeted therapies in human glioma clinical trials.
Our lab has led correlative research for several clinical trials and preclinical trials of novel targeted therapies in gliomas. Analysis of efficacy using next-gen sequencing, array CGH, immunohistochemistry, and MGMT methylation specific PCR testing. Findings of note have included identification of MGMT methylation as a marker of better prognosis in low grade gliomas of all types. In other studies we have studied the role of PI3K/AKT/mTOR and MDM2/TP53 signaling in adult GBM. These studies carried out in collaboration with NCI consortium investigators or as PI initiated trials helped to better understand the trial results and advance the field of integrated biomarker driven trial analysis.
To learn more about our research, see our recent publications.