Pelotonia-Funded Grants Support Key Collaborations
Fifteen teams of faculty scientists received funding boosts through Pelotonia revenue for their innovative research projects during fiscal 2014-15. All 15 were funded by the OSUCCC – James Intramural Research Program (IRP), which is supported by Pelotonia dollars.
A dozen of the funding awards were Idea Grants, one was a Community Partnership Award, one was a Clinical Trial Award (protocol-specific research support) and one was a Bridge Funding Award. All of these grants, which are typically two-year awards of $50,000 per year, are especially important at a time when government funding is hard to obtain for the early pursuit of promising studies.
“There is no routine cancer research, and these creative projects which involve ideas from scientists thinking ‘outside the box’ would not be possible without the thousands of Pelotonia riders and donors who are bringing us closer each day to creating a cancer-free world,” says OSUCCC Director and James CEO Michael A. Caligiuri, MD.
In the past five years, 73 OSUCCC – James research teams have received Pelotonia-supported IRP funding awards totaling about $7.6 million. Awardees are selected through a peer-review process conducted by internal and external scientists not competing for grants in the current funding year. Here are the fiscal 2014-15 IRP awards:
Idea Grants(These grants provide early funding support for highrisk, high-payoff research for which external grants are difficult to obtain.)
Identifying and Developing New Immunoagents for Cancer Diagnosis and Therapy
(PIs: Michael Tweedle, PhD, and Charles Hitchcock, MD, PhD)
This study will develop molecular tools for cancer diagnosis and therapy by targeting nucleoli, a marker abundantly present on the surface of cancer cells but not on normal cells. This research team recently identified an agent that blocks nucleolin, and now the team will investigate the therapeutic potential of this agent on several types of human tumors. The compound also will be attached to tracers that will help clinicians and surgeons identify the tumors, plan the surgical procedure and assess the complete removal of cancer cells from patients, which will improve their overall survival.
Proteasomal Pathway Regulates PTEN Protein Degradation and Promotes Carinogenesis
(PIs: Sarmila Majumder, PhD, and Michael Ostrowski, PhD)
Certain genes, known as tumor-suppressor genes, protect people from cancer and promote response to cancer therapy. PTEN is a tumor-suppressor gene, but it is lost due to the genetic changes that occur in many cancers. Recent studies by this research team suggest that in some breast cancer patients PTEN is lost because the PTEN protein is unstable. The researchers have identified several factors that promote PTEN-protein breakdown; now they will determine how these factors regulate PTEN protein stability and regulate breast cancer initiation and progression. Restoring PTEN protein by blocking these negative regulators could be a novel therapy for many cancers.
TRPV2/Cannabidiol as a Novel Therapeutic Target for Triple-Negative and Metastatic Breast Cancer
(PI: Ramesh Ganju, PhD)
The overall goal of this project is to develop therapies against highly aggressive and metastatic triple-negative breast cancers (TNBC), which are associated with poor prognosis due to early metastasis to other organs and a lack of targeted therapies. This team has preliminary data that shows TNBC growth and metastasis were inhibited in culture and mouse models by a plant-derived compound called cannabidiol, which has been shown to activate an ion channel, transient vanilloid-like receptor 2 (TRPV2). The researchers hypothesize that cannabidiol, upon binding to TRPV2, activates immune cells and increases immune response against tumors. This study will help them further determine the role of TRPV2/cannabidiol in inhibiting growth and metastasis of TNBC.
Develop IL-27-Based Combinational Immunotherapy of Cancer
(PI: Xue-Feng Bai, MD, PhD)
Cancer immunotherapy has emerged as a major weapon in the war against cancer. The increase in response rates following treatment with anti-CTLA-4 antibodies and anti-PD1 antibodies shows the power of combining immune therapy agents. However, because severe autoimmune side effects limit the use of this combination, additional combinations are sought. This team will develop therapeutics that have the potential to boost the effectiveness of cancer immunotherapies, including antibody-based agents and cancer vaccines. The researchers hypothesize that combining IL-27 with anti-PD1 antibodies or cancer vaccines can enhance the effectiveness of those immune therapies while avoiding serious autoimmune side effects.
Ceragenin-Based Therapy for Multiple Myeloma
(PI: Don Benson, MD, PhD)
Myeloma is an incurable form of blood cancer affecting more than 75,000 patients in the United States. Novel treatments that extend patient survival, in part through the body’s immune system, have provided new opportunities to harness the immune system to fight cancer. Recent discoveries suggest that tiny proteins called antimicrobial peptides in the immune system might also have anticancer properties. This grant will enable researchers to learn whether artificial peptides that are based on the naturally occurring immune proteins might offer an entirely new myeloma treatment.
Defining the Role of Autophagy in Anoikis Resistance and in Peritoneal Carcinomatosis/Sarcomatosis
(PIs: James Chen, MD, and John Hays, MD, PhD)
Many cancers can spread throughout the abdomen in a pattern known as carcinomatosis or sarcomatosis. This type of spread indicates the cancer is highly aggressive, but the mechanisms involved in these processes are poorly understood. These researchers have developed a laboratory model that mimics carcinomatosis or sarcomatosis and have shown that, across multiple cancers, a process called autophagy, which can cause cells to self-destruct, is dysregulated. Their initial experiments showed that, by altering the mechanism of autophagy, they can lower the number of cancer cells that survive. This grant will help them study more drugs and cancers to see if they can repeat these effects.
Tumor Suppression and Genome Stability
(PIs: Kay Huebner, PhD, and Daniel Schoenberg, PhD)
Tumor-suppressor genes protect cells from developing into cancer. When these genes are mutated or silenced, they can no longer protect the cell, and this contributes to cancer development. Fhit is a tumor-suppressor gene that is lost in most human cancers, but scientists do not completely understand how or why its loss contributes to cancer. In this study, researchers will identify Fhit-regulated genes that control cell survival, proliferation and invasiveness with the goal of identifying new targets for drugs that might help treat more than 50 percent of all cancer cases.
Improving Chemotherapy Effectiveness in Breast Cancer
(PI: Alo Ray, PhD)
Many kinds of chemotherapy kill cancer cells by damaging the DNA of rapidly dividing tumor cells. However, some cancer cells survive the treatment due to their ability to repair DNA damage and their use of checkpoint signaling pathways. This study will examine ways to disrupt or block DNA repair and cell-signaling pathways that enable cancer cells to survive chemotherapy and radiotherapy treatments. It could define whether blocking a certain signaling pathway in the presence of chemotherapeutic agents improves chemotherapy effectiveness in breast cancer.
Stem Cell Resistance in Chronic Lymphotic Leukemia (CLL)
strong>(PIs: Natarajan Muthusamy, MPH, PhD, and L. James Lee, PhD)
Stem cells are cells that give rise to other cells in tissue. A small proportion of cancer cells also has qualities of stem cells and is thought to play a role in cancer development and resistance to chemotherapy. Leukemia-generating stem cells are widely accepted in myeloid leukemia, but little is known about their role in the most common form of adult leukemia, CLL. These researchers will evaluate a new technology for identifying potential stem-like CLL cells, determining whether they are true leukemia stem-like cells, and then learning more about their biology. Findings could lead to new and more effective CLL treatments.
Defining Prostate Cancer Aggresiveness Through DNA Sequencing
strong>(PIs: Qianben Wang, PhD, and Steven Clinton, MD, PhD)
Research has demonstrated that male hormones called androgens are necessary for the development and progression of prostate cancer. Antiandrogen hormone therapy has been a critical intervention in prostate cancer treatment. Although dramatic responses are often seen, the therapy ultimately fails as the cancer evolves to a treatment-resistant state. How androgens stimulate cancer growth and how resistance to antiandrogens occurs are poorly understood. This study will improve understanding of the molecular and genetic events involved in these processes while helping to define markers that enhance choices of antiandrogens for treating patients. This knowledge could result in the identification of androgen-regulated targets and the development of better treatments.
Stem Cells' Role in Brain Tumor Development and Spread
(PI: Susan Cole, PhD)
Gliomas are the most common tumor of the central nervous system and are difficult to treat, resulting in overall poor treatment outcomes. Researchers at the OSUCCC – James believe that populations of cancer stem-like cells cause these tumors to be resistant to therapy. This project will take a closer look at the tumor microenvironment and cell communication pathways that support these clusters of stem-like cells in an effort to better understand how regulating these pathways could lead to treatments for gliomas.
Resistance of Liver Cancer to Sorafenib: Mechanisms and Development of Strategies to Combat Resistance
(PI: Samson Jacob, PhD)
Liver cancer is the fifth most prevalent cancer in the world and the second leading cause of cancer-related death (particularly in men), with the annual death rate exceeding 500,000. The incidence of liver cancer and mortality is increasing rapidly in the United States. A major problem in treating this cancer is its late diagnosis. Currently, sorafenib is the only approved drug for treating these patients. However, patients quickly develop resistance to sorafenib, which impedes the effectiveness of therapy and results in death shortly after initiating treatment. Therefore, it is important to develop new therapeutic strategies to further extend the survival of these patients. This study will address that issue.
Clinical Trial Award (Protocol-Specific Research Support)
(Clinical trials not only help develop ways to prevent, diagnose and treat cancer, but they also give participating patients access to some of the most advanced treatments available anywhere. Awards in this category support such studies.)
Herpes-Based Virus to Attack Solid Tumors
(PI: Timothy Cripe, MD, PhD)
This team will test a new therapy for treating childhood and young-adult cancer. Oncolytic virus therapy uses live viruses to selectively infect and kill cancer cells with minimal damage to normal tissue. Once inside cancer cells, the anticancer virus is designed to kill those cells as it replicates and spreads to adjacent tumor cells. The goal is more complete and precise treatment of the tumor. This project is a first-in-human study of a locally developed oncolytic virus based on the herpes simplex virus-1. It is the first step toward determining whether the virus can shrink solid tumors outside the central nervous system.
Community Partnership Award
(This category supports investigators who partner with a community entity to conduct a cancer-focused study.)
Mobile Health Intervention for HPV Vaccination
(PIs: Mira Katz, PhD, MPH, and Paul Reiter, PhD, MPH)
Human papillomavirus (HPV) vaccination in young adults of ages 18 to 26 is an effective strategy for reducing the burden of HPV-associated diseases like cervical cancer; however, vaccination rates are suboptimal among this population. In a new pilot study, researchers at the OSUCCC – James, in collaboration with the Wilce Student Health Center, will test a mobile health intervention (i.e., a targeted HPV vaccine narrative on a mobile-friendly website) to communicate with young adults about HPV-associated diseases and the HPV vaccine in an effort to increase uptake of the vaccine in this high-risk population. The study also will obtain preliminary data on whether the narrative format increases HPV vaccine initiation in this age group.
Bridge Funding Award
(These funds assist researchers with competitive renewal applications at the level of an NCI R01 grant or equivalent that were not funded on their first submission. IRP Bridge Funding is also available for competitive renewal of grants whose initial funding has expired.)
A Mass-Spectrometry Approach to Mapping Histone Modification Crosstalk
(PIs: Michael Freitas, PhD, and Mark Parthun, PhD)
Histones are proteins that help package DNA in cells. Specific histone modifications can influence the modification of other histones, generating complex networks of histone-modification crosstalk. This research team will combine a molecular genetics and a mass-spectrometry approach to produce the most comprehensive view of histone cross-interactions to date.