Innovative Research at the Core of Irving Multi-PI Planning Grants
Three multi-disciplinary research teams have been awarded the 2022 Irving Multi-PI Planning Grant, administered by the Herbert Irving Comprehensive Cancer Center (HICCC) and the Irving Institute for Clinical and Translational Research, in conjunction with the Columbia University Clinical Trials Office.
The three teams are led by principal investigators Jeffrey Bruce, MD, professor of neurological surgery at Columbia University Vagelos College of Physicians and Surgeons (VP&S); Daniel Javitt, MD, PhD, professor of psychiatry at VP&S; and Hiroshi Nakagawa, MD, PhD, associate professor of medicine at VP&S. Drs. Bruce and Nakagawa are members of the HICCC.
The annual Multi-PI Planning Grant program supports the submission of multi-component biomedical research grants (e.g., SPORE, U54, P01, P50) and large multi-PI research grants (e.g., NCATS U01, MPI grants that require NIH preapproval). These one-year awards will allow the teams to build out their NIH applications to pursue innovative research across a wide range of conditions and diseases.
The projects will investigate improved methods for drug delivery to target brain tumors, the underlying mechanisms of schizophrenia, and the development of head and neck cancers. The planning grants are part of a larger partnership between the HICCC and Irving Institute that includes programs in therapeutic development, interdisciplinary research, education and training, community outreach and engagement, among others.
Congratulations to the teams on their winning projects.
“Convection-enhanced delivery for brain tumors”
Lead Investigator: Jeffrey Bruce, MD, professor of neurosurgery
Co-Principal Investigator: Peter Canoll, MD, PhD, professor of pathology and cell biology
Co-Investigators: Andrea Califano, Dr, professor and chair of systems biology, professor of biochemistry and of molecular biophysics, and professor of bioinformatics; Andrew Lassman, MD, professor of neurology; Raul Rabadan, PhD, professor of systems biology and of bioinformatics; Peter Sims, PhD, associate professor of systems biology and of biochemistry and molecular biophysics.
Glioblastoma, or brain cancer, is invariably fatal with an average survival of 15 months despite aggressive treatment. A crucial need exists for more effective treatments. Promising chemotherapy for glioblastoma have failed because of tumor heterogeneity, where some tumor cells are not sensitive to a given drug. Another challenge is that most chemotherapy drugs cannot pass into the brain tumor because of problems with drug delivery through the blood brain barrier. The team’s solution is to use convection-enhanced delivery (CED), a novel method of drug delivery that allows drugs to target the tumor and surrounding brain through a surgically placed thin tube connected to a micro-infusion pump. The investigators have already seen success with this method in three clinical trials and propose a CED-centered P01 program project grant to work on optimizing drug delivery and incorporate testing of new anti-tumor compounds.
“Translational mechanistic biomarkers for precision intervention and etiological investigation in first episode schizophrenia”
Lead Investigator: Daniel Javitt, MD, PhD, professor of psychiatry
Co-Investigators: Guillermo Horga, MD, PhD, associate professor of psychiatry; Jia Guo, PhD, assistant professor of neurobiology (in Psychiatry); Joshua Kantrowitz, MD, associate professor of clinical psychiatry; Lawrence Kegeles, MD, professor of clinical psychiatry (in Radiology); Frank Provenzano, PhD, assistant professor of neurological sciences (in Neurology)
Schizophrenia is a major mental health disorder and leading cause of ongoing disability. There is a critical need to better understand the underlying causes of the disease and improve treatment options. The team plans to explore the brain mechanisms that cause psychosis symptoms by developing new neurophysiological biomarkers that are sensitive to dysfunction in specific brain pathways, including the glutamate and dopamine pathways. These systems have been studied separately in people with schizophrenia but have rarely been studied in parallel within the same patient population, or relative to etiological animal models. The interdisciplinary team proposes a P50 Silvio O. Conte Center that will develop an integrated theory of the disease and potentially lead to more personalized approaches to drug development and treatment for people with schizophrenia.
“Understanding and targeting epigenetic and metabolic alternations in HNSCC pathobiology”
Lead Investigator: Hiroshi Nakagawa, MD, PhD, associate professor of medicine
Co-Principal Investigator: Chao Lu, PhD, assistant professor of genetics and development
Co-Investigators: J. Alan Diehl, PhD, professor and chair of biochemistry at Case Western Reserve University; Quintin Pan, PhD, professor of otolaryngology at Case Western; Theodoros Teknos, MD, deputy director at University Hospitals Seidman Cancer Center and professor of otolaryngology at Case Western.
Treatment failure for head and neck squamous cell carcinomas (HNSCC) leading to recurrent/metastatic disease, remains a clinical challenge. In addition, some current standard of care approaches can significantly impact quality of life. There is a pressing need to better understand the biology of the different forms of HNSCC, which are typically driven by alcohol use or human papillomavirus, in order to improve therapy. The team, comprising researchers and clinicians from Columbia and Case Western Reserve University, is preparing for a multi-disciplinary and multi-institutional P01 Research Project Grant application to the National Cancer Institute that will dive deeply into the underlying biology of HNSCC at the molecular level of genomic and metabolic regulation in order to identify new drug targets and build personalized approaches to treating HNSCC.