Forbes Institute for Cancer Discovery announces $500K in grants
The Forbes Institute for Cancer Discovery at the University of Michigan has announced its first round of grant recipients, with $500,000 earmarked to undertake high-risk, high-reward initiatives with the potential to drive new advances in cancer research.
The intent is to fuel rapid development of innovative technology and new therapies, bringing better, more targeted treatments to the 1.6 million Americans diagnosed with cancer each year.
“The greatest discoveries come from crossing the boundaries between the established disciplines,” says Forbes Institute director Max S. Wicha. “The Forbes Institute supports teams of investigators from across the university: the engineering school, the school of pharmacy, the school of public health, the business school, the law school and the medical school.”
Four grants were awarded to research teams, each of which represent multiple University of Michigan schools:
James Moon, Ph.D., John Gideon Searle Assistant Professor of Pharmaceutical Sciences, College of Pharmacy, and Assistant Professor of Biomedical Engineering, College of Engineering was awarded $200,000 for “Towards precision cancer immunotherapy.”
Moon and Anna Schwendeman, Ph.D., are developing a new cancer vaccine technology that can work in synergy with immune checkpoint inhibitors. They have produced ultra-small (~10 nm in diameter) nanodiscs to deliver anti-tumor vaccines. In preliminary studies in mice, the vaccine nanodiscs combined with immune checkpoint inhibitors eliminated tumors within 10 days of treatment in the majority of the mice. In this project, the researchers are now aiming to further develop the technology for personalized cancer vaccination.
"The idea is that these vaccine nanodiscs will trigger the immune system to fight the existing cancer cells in a personalized manner. The Forbes Institute will provide critical support for generating pre-clinical data that will examine this new idea and may promote bench to bedside clinical translation in personalized cancer immunotherapy,” Moon says.
Nouri Neamati, Ph.D., the John G. Searle Professor of Medicinal Chemistry at the College of Pharmacy was awarded $200,000 for “Discovery of next-generation therapeutics through machine learning techniques.”
Identifying potential cancer targets is the early and perhaps most critical step in drug discovery. Neamati’s team built a database of over 20 million small compounds that is searchable in two- and three-dimensions. Using machine learning techniques coupled with intensive bioinformatics analysis they can match pairs of compounds with similar mechanism of actions.
“The Forbes Institute grant will enable us to expand the use of this turnkey technology and to pursue the preclinical development of a very promising compound for the treatment of pancreatic cancer identified in our laboratory.”
Judy Leopold, Ph.D., Research Associate Professor at the Medical School and Co-Director, Experimental Therapeutics Program, University of Michigan Rogel Cancer Center, and Carol Fierke, Ph.D., Jerome and Isabella Karle Distinguished University Professor of Chemistry and Professor of Biological Chemistry in the Medical School, were awarded $50,000 for “Drugging the Undruggable: Design of Novel KRAS Inhibitors by Dual Targeting of the Effector and Allosteric Binding Sites.”
“The KRAS oncogene is the most frequently mutated oncogene in human cancer,” explains Leopold. “However, it has long been viewed as undruggable owing to the complexities associated with directly targeting this protein.”
This project will seek to design and optimize development of small molecule inhibitors of KRAS protein-protein interactions to treat KRAS mutant cancers. Funding from the Forbes Institute will provide assistance to enable the generation of proof of concept data to support this design approach.
Lonnie D. Shea, Ph.D., William and Valerie Hall Chair and Professor, Department of Biomedical Engineering and Jacqueline S. Jeruss, M.D., Ph.D., Associate Professor of Surgery, Director, Breast Care Center were awarded $50,000 for “A synthetic pre-metastatic niche for early metastasis detection.”
Shea’s team has developed an implant that captures early metastatic cells, and the combination of these implants for early detection combined with an early intervention can improve outcomes. Additionally, the team has determined that the attraction of tumor cells to the implant results from the immune cells that are attracted to the implant.
“The detection of immune cells in the implant can potentially be used to identify the initiation of cancer prior to the spread of cells. While many investigators have proposed to sample the blood to look for cancer cells, our approach is unique in that the implant mimics a metastatic site. We are looking to determine whether the site is being prepared for the arrival of cancer cells, which occurs prior to the spread of disease. The properties we measure in the implant are not detectable in the blood.
“The Forbes fund provides the seed to take the basic technology of the implant and develop a novel early diagnostic, which may ultimately enable a molecular staging of metastatic disease.”
During this inaugural year of the Forbes Institute, a second round of grants will be awarded this summer.
The Forbes Institute for Cancer Discovery was founded in June 2016 thanks to a generous $17.5 million gift from Sidney and Madeline Forbes of Bloomfield Hills, Mich. The center’s director is Max S. Wicha, M.D., Madeline and Sidney Forbes Professor of Oncology and director emeritus of the U-M Rogel Cancer Center.