Roy and Diana Vagelos Precision Medicine Pilot Awards 2018-2019
We were impressed with the response and with the broad range of proposals from Columbia faculty. The standard of the 34 applications we received was very high, and investigators came from all Columbia campuses. Thanks to all who submitted proposals and to those who participated in the review process.
The Roy and Diana Vagelos Awards are a cornerstone of the CPMI mission: to establish world class academic research centers of excellence to build precision medicine as a basic and applied science at Columbia. Seeding basic research in precision medicine with these awards is an efficient way of converting this money to external research grants and we look forward to this return on investment in due course.
The three winning proposals reflect the high standard and the broad base of precision medicine basic science research being conducted and conceived at Columbia. They cover epilepsy research; neuro oncology research; and developing a synthetic cell communication tool for tissue engineering.
The winning proposals are:
1. Development of novel therapies for STXBP1 encephalopathy.
Michael Boland Ph.D. Dept of Neurology, Institute for Genomic Medicine; Wayne Frankel Ph.D. Dept of Genetics & Development
Mutations in STXBP1 result in a disorder characterized by infantile epilepsy, severe cognitive impairment, and slow progression in GI and motor development. Medications may control seizures, but have no effect on other aspects of development. In children with only one functioning copy of the gene, there is no correlation between severity of seizures and cognitive impairment suggesting that separate mechanisms are involved. We will study human neuronal and mouse models of STXBP1 haploinsufficiency at the organism, neuronal network, and cellular level in order to identify the most robust features for testing therapies. Screening will be performed on human neuronal networks, and brain region-specific mouse neuronal networks in an effort to identify neuroactive, FDA-approved compounds that correct defects. We will also develop and test two different gene therapy approaches for correcting associated developmental phenotypes.
2. Molecular characterization of gliomas under immunotherapy.
Raul Rabadan PhD, Dept of Bioinformatics; Systems Biology; Fabio Iwamoto MD, Dept of Neurology (Neuro-oncology division); Junfei Zhao, PhD.
Glioblastoma is the most common and most aggressive primary brain tumor in adults, with extremely poor prognosis. While these patients have infrequent tumor responses to immunotherapies compared to melanoma and non-small cell lung cancers, 10% of patients showed limited positive responses. We are extending our current efforts in the molecular characterization of these patients by extensive profiling the genome of the tumor and the surrounding immune cells of a cohort of IDH1 mutant gliomas treated with immunotherapies after standard treatment. These tumors have been reported to have very high rates of mutations (hypermutation), a genomic characteristic that have been associated to response to immunotherapies. Our work will identify novel molecular markers of response to immunotherapies by studying specific cohort of these patients treated at Columbia University.
3. Exploiting the basic mechanism of Notch activation to develop new diagnostic, therapeutic and tissue engineering tools for precision medicine.
Gary Struhl PhD; Paul Langridge PhD. Dept of Genetics and Development (in Neuroscience); Zuckerman Mind Brain Behavior Institute
Synthetic biology involves engineering cells so that they perform useful tasks. An ambitious aim of the field is to customize the behavior of cells so that they form tissues for the repair of wounds, correction of birth defects, regeneration of damaged limbs or creation of organ substitutes. Central to this goal is enabling cells to communicate using tailor-made components. Our research describes the development of a tool for devising and testing this synthetic cell-communication technology. We will establish a system with entirely synthetic cell-communication that functions alongside natural biological processes and determine how these tools can be used to organize cell behavior and alter the morphology of a tissue. In the future such bespoke systems may well be further customized through their application in precision medicine and lead to therapeutic and biotechnological advances that will help fight disease and repair defects.