Idea Grants Support Innovative Thinking in Cancer Research
Pelotonia dollars boosted team science at the OSUCCC – James in 2013 by supporting nine idea grants and one protocol-specific research (PSR) grant. The grants were awarded to teams of faculty researchers who are pursuing early work in basic, clinical/translational or population science that could lead to larger grants from external sources. These grants are especially important because government funding is difficult to obtain for the early pursuit of innovative ideas. The grants were awarded by a scientific review committee of external and internal reviewers that was chaired by the OSUCCC associate directors. The committee considered the scientific merit of competitive applications submitted by the research teams.
CD200R Signaling in Melanoma Progression and Immunotherapy
Xue-feng Bai, MD, PhD; Lai-Chu Wu, PhD
This team’s studies have shown that melanoma cell expression of CD200, a cell-surface glyoprotein, can inhibit melanoma tumor formation and spread. This inhibition appears to be mediated by CD200 receptor (CR200R)-positive myeloid cells. Information generated by this study will help the investigators understand the role of CD200R signaling in causing melanoma and in immunotherapy for this disease, which is the deadliest form of skin cancer.
CS-1-Targeted NK vs. T-Cell Chimeric Antigen Receptor Therapy With or Without Elotuzumab
Jianhua Yu, PhD; Craig Hofmeister, MD
Researchers hypothesize that targeting CS-1, an antigen that is highly expressed on multiple myeloma (MM) cells, by a specific type of the body’s immune cells, either alone or in combination with other immune cells or a drug called elotuzumab, is a promising therapeutic strategy for patients with MM, a currently incurable cancer of white blood cells called plasma cells. This team will test its hypothesis in both in vitro studies and in vivo model systems to lay the foundation for a phase I clinical trial for patients with relapsed MM using each patient’s own immune cells.
Tethered Cationic Lipoplex Nanoparticle (TCLN) Assay for Early Lung and Liver Cancer Detection and Surveillance via Extracellular RNAs in Exosomes and Circulating Tumor Cells
L. James Lee, PhD; Patrick NanaSinkam, MD; Kalpana Ghoshal, PhD; Michael Paulaitis, PhD; Carl Schmidt, MD
This team has developed a low-cost “Tethered Cationic Lipoplex Nanoparticle (TCLN)” biochip that may provide a patient-friendly early detection and surveillance assay for lung and liver cancer by detecting circulating tumor cells or extracellular RNAs in patient blood samples. The team will evaluate the feasibility of this technique in animal-model and patient samples, then use the data to submit two grant proposals to the NCI in two years and a third proposal in the future.
STAT3 as a Mediator of Immune Suppression in the Pancreatic Cancer Stroma
Gregory Lesinski, PhD, MPH; Michael Ostrowski, PhD
A hallmark of pancreatic cancer is a network of pancreatic stellate cells (PSCs) that arise from chronic inflammation and surround each tumor to help it grow while suppressing the immune system. This team seeks to understand how PSCs influence immune suppression in pancreatic cancer so they can prioritize cellular targets and manipulate them to enhance immunotherapy. They believe a gene called STAT3 in PSCs plays a key role in immune suppression, a hypothesis they will test by developing a mouse model of pancreatic cancer so they can study how STAT3 promotes PSC survival and use these data for a future NCI grant application.
Novel Small Molecule Inhibitor of PHD3 Effects on Human Breast Cancer Metastasis and Migration on Nanoscale Variable Modulus Devices
Tim Eubank, PhD; John Lannutti, PhD
In search of better treatments for triple-negative breast cancer (TNBC) – an aggressive and often fatal form of the disease that accounts for about 15 percent of all breast cancers – this team has discovered a pathway activated by a small molecule inhibitor of an enzyme called prolyl hydroxylase 3 (PHD3), which is thought to play a part in TNBC tumor metastasis (spread). The team will study the ability of their PHD3 inhibitor to reduce the metastatic potential of TNBC cells in an animal model. This study will use nanoscaled tools originating within the Nanoscale Science and Engineering Center at Ohio State.
Insulin Receptor Splicing in Response to Hypoxia and Drug Resistance: A Pilot Study
Dawn Chandler, PhD; Peter Houghton, PhD
Solid tumors are characterized by hypoxia (oxygen deficiency), and the ability of the tumor cells to adapt to hypoxia is essential for tumor progression. This study seeks to understand the mechanisms and consequences of insulin receptor (IN-R) gene splicing, or natural chemical alteration of DNA, in response to hypoxia – testing the hypothesis that splicing factors are modulated in response to hypoxia and are thus involved in the alternative splicing of the IN-R gene that contributes to tumor formation. The team has developed a splicing method that mimics cells that have undergone hypoxia. They will use this to study regulatory mechanisms for this process in hopes of finding targets for therapeutic intervention.
PRMT5 Dysregulation as a Driver Event in Richter’s Transformation
Rosa Lapalombella, PhD; Robert Baiocchi, MD, PhD
Richter’s transformation (RS) is a complication of chronic lymphocytic leukemia (CLL) in which the leukemia changes into a rapidly proliferating and aggressive form of lymphoma with a poor prognosis despite the use of standard lymphoma therapy. The cause(s) of this transformation is not well understood. This team hypothesizes that dysregulation of a protein called PRMT5, which is variably expressed in CLL and overexpressed (overly active) in RS, is a driver event in CLL transformation to lymphoma. Using gene- and RNAsequencing methods, they hope to shed light on how PRMT5 dysregulation causes the transformation. This information may lead to new therapeutic approaches to RS.
Gene Discovery Using a Drosophila Tumor Model
Amanda Simcox, PhD; Victor Jin, PhD
Because the RAS gene signaling pathway is implicated in multiple cancers, an intense effort is under way to study RAS regulators and effectors. This team has developed a conditional RAS-driven tumor cell model in fruit flies that they will use to discover genes in the RAS pathway and also to investigate tumor cell dormancy, which is important because, in this state, the cells evade cancer therapies that target proliferating cells. These dormant cells need to be killed too, because they can later cause cancer recurrence.
The Role of the Epstein-Barr Virus in NK-Cell Lymphoma
Aharon Freud, MD, PhD; Robert Baiocchi, MD, PhD; Pierluigi Porcu, MD
Extranodal natural killer (NK) cell lymphoma, nasal type (ENKL) is an aggressive disease that stems from the Epstein-Barr virus (EBV) infecting and transforming NK immune cells. Very little is known about how this rare form of invasive cancer develops, and even less is known about the mechanisms of drug resistance that limit the effectiveness of chemotherapy for patients with ENKL. Based on hypotheses stemming from their earlier work, this team will develop laboratory models to study mechanisms of EBV-induced NK cell transformation and to characterize the body’s immune response to ENKL for therapeutic purposes.
Tangerine Tomato Phytochemical Bioavailability and Metabolism in Men With Prostate Cancer
Steven Schwartz, PhD
This study will determine whether the tangerine-type tomato should be the principal tomato used in the university’s ongoing tomato-soy juice project targeted toward prostate cancer. The tangerine tomato is a unique cultivar bred at Ohio State that accumulates a natural substance called lycopene in a form that is more bioavailable than that in red tomatoes. Pelotonia funding will support a clinical trial in which men with prostate cancer who are about to undergo prostate removal will be assigned to a low-lycopene diet or consume two servings of either tangerine tomato juice or red tomato juice for four weeks before surgery. Data on the absorption and biodistribution of lycopene will affect study design for an NIH grant renewal application in 2014.