Boston University’s Mark Grinstaff has been awarded a new National Institute of Health/National Cancer Institute (NIH/NCI) R01 grant. The funding will be used in collaboration with University of North Carolina Greensboro (UNCG), Augusta University, Brigham and Women’s Hospital (BWH) and Mycosynthetix. The five year grant is to study the development of a combination therapy that would tackle the problem of drug resistance in cancer, which is the primary cause of treatment failure in aggressive peritoneal cancers such as mesothelioma.
Specifically, drug-resistance occurs in up to 85% of these patients with five-year survival rates for mesothelioma patients remaining dismal at less than 15%. This grant will enable a multidisciplinary team of researchers and physicians to work on a highly innovative therapy which uses an epigenetic modifying agent called Verticillin A in combination with traditional chemotherapeutic agents to treat mesothelioma. Verticillin A, a natural product produced by fungi, provides a unique mechanism of action that enables it to overcome drug resistance by inducing reexpression of epigenetically silenced tumor suppressor genes. This allows it to both re-sensitize drug resistant cancer cells and to potentiate the effect of traditional chemotherapeutics. To achieve tumor-specific delivery of Verticillin A, the team uses a novel expansile nanoparticle that leverages a unique Materials-Based Targeting strategy.
Dr. Grinstaff is the Distinguished Professor of Translational Research, Biomedical Engineering, Chemistry, Materials Science and Engineering, and Medicine as well as the Director of the NIH T32 Program in Biomaterials and the Director of the Nanotechnology Innovation Center at Boston University. The idea for the project started to form after a meeting three years ago at UNCG where Dr. Nicholas Oberlies introduced Dr. Grinstaff to Dr. Cedric Pearce of Mycosynthetix and Dr. Kebin Liu, Professor in the Department of Biochemistry and Molecular Biology at Augusta University, to discuss the therapeutic potential of Verticillin A in the treatment of cancers. Dr. Pearce is the founder and CEO of Mycosynthetix, which has the largest repository of filamentous fungi in the world, with 50,000+ isolates. Dr. Oberlies and Pearce are long-time collaborators on projects to investigate the Mycosynthetix library of filamentous fungi for anticancer drug leads and developed methods to isolate and purify Verticillin A.
The leadership team on this project includes Dr. Grinstaff’s long-time collaborator, Dr. Yolonda Colson, who is the Associate Administrative Chief of the Division of Thoracic Surgery at Brigham and Women’s Hospital/Dana-Farber Cancer Center (BWH/DFCI), Professor of Surgery at Harvard Medical School, and Executive Director of the Center for Surgical Innovation. She will lead the team of researchers at BWH/DFCI. Drs. Grinstaff and Colson have collaborated for over a decade on dozens of papers and presentations and NIH-sponsored research projects.
The leadership group held a kick-off meeting at Boston University on June 28, 2018. The investigators discussed the time-line and immediate goals of the project and potential clinical application of Verticillin A for the treatment of mesothelioma.