What's the Big Idea?

Pelotonia Grants Help Researchers Answer That Question

Twenty teams of faculty scientists received fiscal 2014 Pelotonia-funded “Idea Grants” that will enable them to develop innovative cancer research studies for which they may later seek large external grants. These “Idea Grants” – each worth $100,000 over two years – are especially important at a time when government funding is hard to obtain for the early pursuit of promising studies. The grants were awarded by a scientific committee of internal and external reviewers. Chaired by the OSUCCC associate directors, the committee considered the scientific merit of applications submitted by the research teams. Here are the fiscal 2014 “Idea Grants”:

Delivering an AML Drug in Nano-Sized 'Fat Bubbles'

(Principal investigators [PIs]: Robert Lee, PhD, and Andrienne Dorrance, PhD)
The drug bortezomib has potential to help patients with acute myeloid leukemia (AML), but the drug is only weakly effective in its current form. Researchers will develop a delivery system by packing the drug into nano-sized bubbles of fat and attaching them to a homing device that seeks out leukemia cells. Study data will determine whether this approach is suitable for testing in humans.

Social Isolation's Role in Breast Cancer Development and Progression

(PIs: Courtney DeVries, PhD; Maryam Lustberg, MD; Cynthia Timmers, PhD)
Studies show that women with breast cancer who are socially isolated have worse outcomes. This team will examine whether loneliness and isolation alter cancer-related gene activity in breast tissue. This information could reveal new diagnostic, therapeutic and prognostic tools for breast cancer prevention and treatment.

Mental Health, Stress and the Response to Cancer Treatment

strong>(PIs: Amy Johnson, PhD, and Barbara Andersen, PhD)
This project will assess stress, depression and quality of life in patients with chronic lymphocytic leukemia who are treated with ibrutinib, a drug that has been studied extensively in clinical trials at the OSUCCC – James. Examining the relationship between cancer growth factors and psychological function may help doctors make treatment decisions by identifying patients at risk for poor outcomes.

Biomarker-Based 2-Drug Therapy for Acute Myeloid Leukemia

(PI: Alison Walker, MD)
Overall survival is low for pediatric and adult patients with acute myeloid leukemia (AML) on standard chemotherapy, but this phase I clinical trial will test a two-drug approach that could significantly increase remission in AML patients. The drugs involved are AR-42, which was developed at Ohio State, and decitabine. This strategy may help more AML patients achieve complete remission.

Studying Health Disparities in 100,000 Underserved in America

(PIs: Electra Paskett, PhD, MSPH; Peter Shields, MD; Mira Katz, PhD; Paul Reiter, PhD; Eric Seiber, PhD; Mike Pennell, PhD)
A Pelotonia Idea Grant will support a project that aims to establish a cohort of 100,000 underserved people from four U.S. populations – African-American, Appalachian, Asian and Hispanic – to better understand the causes of cancer disparities in the United States. The grant will help with recruiting study participants and with forming a coordinating center to collect and analyze data and biospecimens from the OSUCCC – James network of collaborating recruitment sites.

Targeting Oncogenes for New Liver Cancer Drugs

(PI: Kalpana Ghoshal, PhD)
Developing drugs that can penetrate the liver and target cancerous cells has been challenging. Researchers in this study will conduct preclinical tests to determine the effectiveness of new drugs that target two oncogenes and a tumor-suppressing microRNA called miR-122 that is critical for normal liver function. Study results could lead to a phase I clinical trial for liver cancer patients.

Understanding Molecular Crosstalk Driving Aggressive Breast Cancer

(PI: Ramesh Ganju, PhD)
Having a better understanding of molecular pathways that contribute to cancer could help scientists identify points in the pathways to intervene and curb cancer development. This project will further characterize the role of proteins in two targeted pathways to shed light on breast cancer growth, blood vessel formation and tumor spread.

Brain Inflammation, Depression and Anxiety in Breast Cancer Patients

(PIs: Courtney DeVries, PhD, and Maryam Lustberg, MD)
Inflammatory changes in the brain could be a primary cause of depression and anxiety commonly experienced by breast cancer survivors, particularly when undergoing chemotherapy. This team will study whether reducing brain inflammation using a well-tolerated drug called minocycline reduces depression and anxiety during chemotherapy.

Digital Image Analysis, Targeted Therapies for Glioblastoma

(PIs: Metin Gurcan, PhD; Jose Otero, MD, PhD; Brad Elder, MD; Vinay Puduvalli, MD; Jessica Winter, PhD)
Despite aggressive treatment, patients with glioblastoma, the most common and deadly of primary brain tumors, live an average of only 15 months. This team is developing advanced image analysis techniques to help guide decisions in patient treatment before and after brain surgery. This technology could guide personalized treatment based on the molecular characteristics of each tumor via unbiased quantitation of signal transduction cascades in tumor cells.

Tackling Treatment-Resistant Prostate Cancer

(PIs: Qianben Wang, PhD; Steven Clinton, MD, PhD)
When prostate cancer returns after surgery and initial androgen-deprivation therapy, it often no longer responds to drug treatment. For this study, OSUCCC – James researchers will identify genes that castration-resistant prostate tumors need to grow and that could be new targets for prostate cancer drugs. The findings may lead to new treatments for prostate tumors that currently have no effective therapy.

Preparing for Resistance

(PI: Sameek Roychowdhury, MD, PhD)
OSUCCC – James researchers have designed a phase II clinical trial to test a drug called ponatinib that inhibits certain genes that drive cancer. Anticipating that cancer cells may develop resistance to ponatinib in this trial, this team will collect biopsy samples from each participant’s tumor before and after treatment, then sequence 20,000 genes in each sample and look for gene changes that could lead to drug resistance.

A Plant Component That Might Help Immune Cells Control Cancer

(PI: Jianhua Yu, PhD)
Can a substance from edible plants boost the cancer-cell killing activity of a type of immune cell? This study will investigate the ability of a substance called phyllanthusmin C (PL-C) to stimulate the activity of natural killer (NK) cells. The researchers hope to show that PL-C in the diet will help NK cells control acute myeloid leukemia and other cancers.

Probing a New Target in Triple-Negative Breast Cancer

(PIs: Robert Brueggemeier, PhD; Harold Fisk, PhD; Chenglong Li, PhD; Pui-Kai Li, PhD; Yasuro Sugimoto, PhD)
Triple-negative breast cancer (TNBC) is an aggressive disease defined by the absence of estrogen, progesterone and HER2 receptors. Without these molecules to target, the usual breast cancer drugs are ineffective for treating TNBC. This team will design and develop drugs that inhibit a molecule called Mps1/TTK as a promising treatment for TNBC and other aggressive breast cancers.

A New Approach to Cervical-Cancer Prevention

(PIs: Paul Reiter, PhD, MPH; Mira Katz, PhD, MPH)
Several types of human papillomavirus (HPV) cause cervical cancer, but the disease is largely preventable through regular screening. This team will develop a pilot program for HPV self-testing among women in Appalachia who have undergone little if any cervical cancer screening. Results will identify the best strategy for improving cervical cancer screening among this population.

Personaliznig Multiple Myeloma Treatment

(PI: Mitch Phelps, PhD; Ming Poi, PharmD, PhD; Craig Hofmeister, MD)
A treatment using stem cell transplantation plus high doses of a drug called melphalan often prolongs the lives of patients with multiple myeloma (MM) and stops disease progression, but patients have variable side effects and response. This team is developing a procedure to personalize dosing of melphalan to improve its effectiveness in killing MM cells while minimizing the drug’s harsh side effects.

A Wearable Guidance System for Better Cancer Surgery

(PIs: Ronald Xu, PhD; Michael Tweedle, PhD; Alper Yilmaz, PhD)
Tools that could help surgeons determine where a tumor ends and healthy tissue begins, and that could help detect hidden cancer cells, could greatly reduce cancer recurrence rates and improve long-term outcomes of patients after cancer surgery. This project will help develop and test a guidance system worn during surgery to identify surgical margins and guide the removal of tumors.

Increasing Insight Into Chemotherapy Side Effects

(PI: Kristen Carpenter, PhD)
Pelotonia funds will support a clinical trial to learn if there is a correlation between chemotherapy treatment and side effects that include fatigue, nausea, vomiting, sensory neuropathy, pain, depression and insomnia. It will investigate whether individual differences in psychological/behavioral variables, such as patient optimism and coping, might influence these side effects. Findings could provide insight into which patients might be most vulnerable to debilitating chemotherapy side effects and strategies that might alleviate them best.

Reversing Drug Resistance in Ovarian Cancer

(PIs: Jeffrey Parvin, MD, PhD, and David Cohn, MD)
These investigators have found that a protein called histone deacetylase 10 (HDAC10) is part of a DNA repair system that may allow some ovarian cancer cells to survive chemotherapy used to treat the disease. They will examine whether drugs called HDAC inhibitors will knock out the HDAC10-powered DNA repair system and knock out a pathway that makes ovarian cancers become drug resistant.

Arresting a Gene That might Drive Esophageal Cancer

(PIs: Zui Pan, PhD; Tong Chen, MD, PhD)
This team hypothesizes that the hyperactive Orai1 gene causes abnormal changes in calcium levels in cells and contributes to esophageal cancer progression. They also believe that inhibiting the over-activity of this gene could help control the disease. They will conduct experiments to reveal more about the role of Orai1 in esophageal cancer, the sixth-leading cause of cancer death worldwide.

Targeting Two Genes Might Improve Melanoma Treatment

(PIs: William Carson III, MD; Albert de la Chapelle, MD, PhD; Ann-Kathrin Eisfeld, MD)
About 40 percent of all patients with melanoma, the deadliest form of skin cancer, have a mutation in a gene called BRAF. This team will investigate BRAF-mutated melanoma and the role of a gene called microRNA-3151. Their project will explore the mechanism of microRNA-3151 and evaluate whether BRAF-inhibiting drugs might more effectively treat melanoma when combined with drugs that inhibit miR-3151.

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