Pelotonia Funds Support 40 New Student Research Fellowships at Ohio State

October 21, 2019
Laboratory Closeup

COLUMBUS, Ohio ­– Forty new faculty-mentored student research projects are underway at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) thanks to funds generated by Pelotonia, an annual grassroots cycling event that has raised more than $200 million in support of cancer research at the OSUCCC – James.

The OSUCCC – James has awarded more than $17 million for 525 student research scholarships through the Pelotonia Research Fellowship Program in the past 10 years. Undergraduate, graduate and postdoctoral fellows are paired with a faculty mentor from one of the OSUCCC – James’ five core research programs.

Recent student research projects include:

Postdoctoral Fellows

New Targets for Preventing Pancreatic Cancer Progression

Investigator: Debasis Nayak of Odisha, India, mentored by Rajgopal Govindarajan, DVM, PhD, OSUCCC – James Translational Therapeutics Program

The goal of this project is to understand the role of solute carrier (SLC) transporters during the process of epithelial-mesenchymal transition (EMT), which enables pancreatic cancer to metastasize and leads to poor response to chemotherapy. A better understanding of this molecular process will provide important information to aid in the development of novel therapies for pancreatic cancer. Researchers will identify specific SLC transporters that promote invasive properties in cancer cells, and then conduct experiments to better understand the molecular mechanisms that promote metastasis. Researchers will use this information to target these SLCs to limit pancreatic cancer metastasis and chemoresistance.

Improving Hospice Transitions at End-of-Life

Investigator: Laura Prater of Mentor, Ohio, mentored by Seuli Brill, MD, Ohio State Department of Internal Medicine, and Thomas Wickizer, PhD, Ohio State College of Public Health, Division of Health Services Management & Policy

Many people who die from cancer are inadequately prepared to receive end-of-life care and are poorly equipped for transitions to hospice. This can result in significant distress for caregivers, increased rates of hospitalization and unwanted aggressive medical interventions for the patient. The goal of this study is to identify key factors toward achieving a successful hospice transition for advanced cancer patients. Takeaways from the study will allow experts to build a translational, evidence-based approach to guide the process. Researchers will also use this knowledge to guide policy and organizational recommendations for end-of-life communication to improve transitions to hospice. The goal of this work is to ensure that the highest quality care is delivered to the most vulnerable patients and their caregivers through each step in the continuum of care.

New Targets in Large B-cell Lymphoma

Investigator: Youssef Youssef of Columbus, Ohio, mentored by Lapo Alinari, MD, PhD, OSUCCC – James Leukemia Research Program

This study will focus on gaining a better understanding of the function of a protein called TBL1 in diffuse large B cell lymphoma (DLBCL), a form of blood cancer with variable patient outcomes. DLBCL patients have different expression levels of some genes called oncogenes. One of the most important oncogenes in DLBCL is C-MYC because it can transform a normal cell into a cancer cell and also can help cancer cells survive. In addition, patients with abnormally high C-MYC expression have a particularly poor prognosis and do not respond well to chemotherapy. Researchers in this study found a new link between TBL1 and C-MYC in which inhibiting TBL1 leads to a decrease in C-MYC level and cancer cell death. This research team will work to evaluate and characterize the new TBL1/ C-MYC pathway so they can develop a drug to target it and prevent uncontrolled cancer cell growth. If successful, this would represent a new targeted therapeutic approach for patients affected by this incurable and aggressive form of cancer.

Understanding Acute Myeloid Leukemia Tumor Microenvironment

Investigator: Amina Abdul-Aziz of Austria, Vienna, mentored by John Byrd, MD, OSUCCC – James Leukemia Research Program

Disease progression in acute myeloid leukemia (AML) is heavily influenced by the characteristics of the tumor microenvironment. In this study, researchers will focus specifically on the role of cells that have stopped growing and dividing but remain viable and metabolically active (known as senescent bone marrow cells). The accumulation of senescent cells is a hallmark of aging; however, these cells are also believed to promote tumor development and progression. Bone marrow mesenchymal stromal cells (BMSCs)—another instrumental type of cells in the AML tumor microenvironment—are hijacked by leukemia cell during leukemia development. In this study, researchers will comprehensively examine the epigenetic age of BMSCs, AML tumor cells and surrounding T cells. Their goals are to provide a quantitative measure of senescence in elderly AML patients, enhance risk stratification and identify novel age-related targets in AML.

Investigating Oncogenic Retroviruses

Investigator: Laura Baltierra Jasso of Mexico City, Mexico, mentored by Kristine Yoder, PhD, OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program

Retroviruses permanently incorporate their DNA into the host genome, which is an advantageous feature for gene therapy. However, retroviruses can dysregulate oncogenes after DNA insertion. Retroviral gene therapy has successfully treated genetic diseases, but treatment-induced leukemia has been observed in patients in clinical trials. Therefore, integration location is decisive for cancer development and crucial to produce safer gene therapy. This study seeks to describe integration dynamics of oncogenic retrovirus and find clues on how integration site selection contributes to oncogenesis.

Graduate Fellows

Microsatellite Instability in Human Cancer

Investigator: Russell Bonneville of Grove City, Ohio, mentored by Sameek Roychowdhury, MD, PhD, OSUCCC – James Translational Therapeutics Program

Microsatellite instability (MSI) is a particular pattern of genetic changes in which short repeating regions (known as microsatellite loci) divide without regulation. This can occur sporadically or in association with inherited genetic disorders such as Lynch syndrome. MSI is frequent in several human cancer types, most commonly endometrial and colorectal. MSI testing is routinely performed in patients with these types of cancer. Recent research suggests knowledge about MSI could also aid in predicting response to immune-enhancing therapy and prognosis. In this study, researchers will use next generation sequencing data to characterize MSI prevalence in other cancer types beyond Lynch syndrome-associated cancers. Knowledge gained through this study could enhance understanding of MSI and improve detection of MSI in additional cancer types.

Cell Fate Decision in Acute Myeloid Leukemia

Investigator: Swagata Goswami of West Bengal, India, mentored by Natarajan Muthusamy, DVM, PHD, OSUCCC – James Leukemia Research Program

Acute myeloid leukemia (AML) is a lethal blood cancer in which immature immune cells grow out of control. New treatment approaches are critically needed for this disease, which has a five-year survival rate of only 25% and median survival of less than one year in patients over 65 years old. In this study, researchers will examine new pathways of leukemia cell survival. Specifically, they will further study a potential new target (protein phosphatase 2A) and its role in cell growth and differentiation in AML.

Cognitive-Behavior Intervention for Shortness of Breath for Lung Cancer Patients

Investigator: Stephen Lo of Boston, Mass., mentored by Barbara Andersen, PhD, OSUCCC – James Cancer Control Program

Shortness of breath (dyspnea) is a common and debilitating symptom for patients with lung cancer and is the reason for one third of emergency room visits among these patients. Previous research has focused on the biologic mechanisms of this condition, but resulting treatments are limited in their effectiveness. In this study, researchers propose a disease-specific cognitive-behavioral model for dyspnea to better understand how a patient’s anxiety and cognitive state interact and lead to decreased physical activity, resulting in less physical strength and worsened dyspnea. Patients will be interviewed about their experiences with cancer and dyspnea. Researchers will then test a behavioral intervention to reduce dyspnea and related symptoms in patients with lung cancer.

Potential Target for Rhabdomyosarcoma

Investigator: Matias Montes of Santiago, Chile, mentored by Dawn Chandler, PhD, OSUCCC – James Molecular Biology and Cancer Genetics Program

P53 is a gene involved in regulating the cell cycle and acts as a tumor suppressor, stopping abnormal cells from forming or growing. Research has shown that some forms of cancer are linked to a mutations in the P53 gene that instead allow cancer cells to grow. In this study, researchers will analyze cell signaling pathways to explore a specific microRNA (miR29b)that appears to act as a tumor suppressor, stopping the growth of cancer cells in some cancers. In rhabdomyosarcoma, however, this gene appears to be “shut off,” allowing cancer cells to grow. The goal of this study is to gain a better understanding of how MDM2 gene alternative splicing affects the P53 tumor-suppressor gene.

Understanding Specific Long Non-Coding RNA Associated with Cancer

Investigator: Duc Phan of Ho Chi Minh City, Vietnam, mentored by Venkat Gopalan, PhD, OSUCCC – James Molecular Biology and Cancer Genetics Program

Long non-coding RNAs have associated with various types of cancer. Thus, they become potential targets for cancer treatment. In this study, researchers will look at how long non-coding RNA is generated and potential strategy to inhibit this process, which may be useful for cancer treatment.

Understanding Chemoresistance in Osteosarcoma

Investigator: Sanjana Rajan of Chennai, India, mentored by Ryan Roberts, MD, PhD, OSUCCC – James Translational Therapeutics Program

For a long time, the cells within a tumor were thought to be similar to one another, like a bowl of chocolate chips. However, scientific studies have identified that a patient’s tumor cells are highly diverse, more like different colored candies in a bowl. A direct implication of this diversity is therapeutic failure as some cancer cells can survive the selective pressure from chemotherapy, causing patients to have relapsed tumors. Researchers and clinicians need to be able to identify these cells to target them up front along with chemotherapy in order to eliminate resistance. The real question, however, is, “What is the target: a group of cells that were resistant to begin with (prior to treatment), or an acquired physiological response that gives some cells a survival advantage? This fundamental question remains unanswered, largely due to limitations in the technology needed to trace and profile gene phenotypes in cancer cells. In this study, researchers will test a method of bridging this technology gap, specifically studying IL6 signaling in cells thought to potentially drive chemoresistance in osteosarcoma.

Chemotherapy’s Impact on Daily Rhythms in Cognition and Immunity

Investigator: Kyle Sullivan of Bristow, Virginia, co-mentored by Leah Pyter, PhD, OSUCCC – James Cancer Control Program, and Karl Obrietan, Ohio State Department of Neuroscience

Breast cancer patients who receive chemotherapy frequently report fatigue, sleep disruption and cognitive deficits, i.e. “chemobrain.” All of these side effects are impacted by biological circadian (24-hour) rhythms. Irregular circadian rhythms, such as flattened levels of circulating cortisol, are associated with worse behavioral outcomes in cancer patients. While many causes of chemobrain have been suggested, the mechanisms behind the behavioral complications of cancer are still unclear. The goal of this study is to understand the extent to which chemobrain symptoms are due to changes in rhythmicity in both the brain and immune tissues relevant to cognitive function. Researchers will model how chemotherapy causes changes in circadian rhythms and memory recall. The study is expected to increase oncologists’ understanding of how cognitive deficits can persist following breast cancer treatment.

Using Peptides as Anti-Metastatic Drugs in Cancer

Investigator: Zechariah Thompson of Mt. Vernon, Ohio, mentored by James Cowan, PhD, Ohio State Department of Chemistry and Biochemistry

Overall disruption in the attachment of certain carbohydrates to proteins and lipids has been linked to a variety of diseases, including aggressive cancers. One specific antigen, CD15s, mediates cellular adhesion. When overexpressed on cancer cells, it has been reported to result in aggressively metastatic disease, resulting in poor outcomes and prognosis. In this study, researchers will look at the specific cellular processes of binding and removing CD15s to better understand the mechanisms that lead to aggressive metastatic disease. Knowledge gained from this study could help scientists explore peptide-based anti-metastasis therapies and diagnostics.

Determining How BPA Exposure in utero Increases Breast Cancer Susceptibility

Investigator: Clarissa Wormsbaecher of Lake Orion, Mich., mentored by Craig Burd, OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program

Endocrine disrupting compounds (EDCs) are chemicals found in the environment that disrupt hormone signaling. Exposure to certain EDCs can mimic estrogen and increase a woman’ chances of developing estrogen-sensitive cancers. Bisphenol A is a common EDC used in the production of plastics, food can linings, dental sealants and other commercial products. It is so prevalent, it can be found in human serum, urine and amniotic fluid, which indicates in utero exposure. Preclinical studies have shown that in utero BPA exposure increases mammary tumors in rodents. More research is needed to understand if this same susceptibility exists for humans. In this study, researchers will seek to identify BPA-induced changes that increase susceptibility to cancer.

Reversing Chronic Lymphocytic Leukemia-Induced Immune Dysfunction

Investigator: Max Yano of Columbus, Ohio, co-mentored by John Byrd, MD, and Natarajan Muthusamy, DVM, PhD, both of the OSUCCC – James Leukemia Research Program

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia and can lead to other challenges, including immune suppression, infections and secondary cancers. Infection is the most common cause of death in CLL patients. Treatments have improved radically over the last five years; however, the disease is still considered incurable but manageable. In this new study, researchers will investigate an immune checkpoint molecule called CTLA4 and its role in CLL immune dysfunction. The goal of the study is to broaden understanding of non-T cell CTLA4 expression in cancer. This knowledge could help enable development of therapies that target CTLA4 expression and immune-stimulating therapies for CLL and other cancers that express CTLA4.

NMD Regulation and Its Role in Cancer

Investigator: Zhongxia Yi of Hubei, China, mentored by Guramrit Singh, PhD, Ohio State Department of Molecular Genetics

In cancer cells, genes that would normally stop the growth of cancer cells are often deactivated by nonsense mutations, which cause their mRNAs to be rapidly degraded by nonsense-mediated mRNA decay (NMD). Existing knowledge about NMD suggests it is a promising therapeutic target for cancer as well as many genetic diseases. However, inhibiting general NMD is highly toxic. The goal of this study is to increase overall scientific understanding of NMD regulation in cells to gain knowledge that could advance this as a new target for cancer therapeutics.

Undergraduate Fellows

Evaluating LCN2 Expression of Myeloid-Derived Suppressor Cells in the Pancreatic Cancer Tumor Microenvironment

Investigator: Kriti Agrawal of Centerville, Ohio, mentored by Thomas Mace, PhD, OSUCCC – James Translational Therapeutics Program

Pancreatic cancer is an aggressive cancer often diagnosed in a metastatic state, preventing many patients from undergoing surgery as a treatment option. In this study, researchers will investigate the relationship between a subset of immune cells—myeloid-derived suppressor cells (MDSCs)—and protein lpocalin-2 (LCN2), both of which are elevated in pancreatic cancer. The team will also investigate whether LCN2 expressed by MDSCs promote tumor-derived fibroblast growth. By gathering a better understanding of these underlying cellular mechanisms, researchers hope to identify ways to improve early diagnosis and treatment.

Evaluating a New Targeted Therapy Approach in Acute Myeloid Leukemia Treatment

Investigator: Hussam Alkhalaileh of Dublin, Ohio, mentored by Gregory Behbehani, MD, PhD, OSUCCC – James Leukemia Research Program

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow that causes uncontrolled growth of immature white blood cells that crowd out “normal” disease-fighting white blood cells. Without healthy levels of normal white blood cells, a person’s natural ability to fight off disease is reduced. AML is especially difficult to treat due to the large number of genetic mutations known to drive the disease. Targeted drug therapies are available for several of these genetic mutations, but hematologists need ways to predict which therapy will work best based on each patient’s subset of cancer characteristics. In this study, researchers will use a custom cell culture system, developed at Ohio State, to grow AML cells in the presence of five FLT3 gene-targeted drugs while maintaining rare cell populations of AML that which are known to mediate patient relapse. Then researchers will use mass cytometry to analyze the cell markers and signaling pathways of these AML cells to determine how they respond to treatment. This analysis will be conducted on AML samples harboring an FLT3 mutation and other commonly co-occurring mutations to explore the different responses of various mutation backgrounds. Investigators expect knowledge gained from this study will enhance personalized treatment for AML and potentially guide hematologists in therapy selection.

Heart Rate Variability as a Predictor of Future Cognitive Decline in Breast Cancer Patients

Investigator: Jacqueline Caputo of Aurora, Ohio, mentored by Janice Kiecolt-Glaser, PhD, of the OSUCCC – James Cancer Control Program

Heart rate variability (HRV) is a measure of the variation between heartbeats. Higher HRV indicates health and the ability to adapt appropriately to environmental challenges. Research suggests lower HRV could indicate or predict cardiovascular or cognitive impairments. HRV and cognitive ability are related through a pathway that starts in the part of the brain responsible for executive functioning, attention span and working memory. In this study, researchers will evaluate high HRV as a potential protective factor that shields breast cancer survivors from cognitive decline during cancer treatment. If HRV can be used to predict the extent of cognitive decline, oncologists could work to improve HRV before providing secondary cancer treatment (for example, chemotherapy, radiation or hormone therapy) with intentional interventions such as exercise.

The Impact of Social Isolation on Tumor Progression and NK Cell Development

Investigator: Logan Chrislip of Milford, Ohio, mentored by Lei Cao, PhD, OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program

It is difficult to universally target treatment for all types of cancer because it is a diverse set of diseases. The bulk of current cancer research focuses on molecular therapies and drug-based treatments, which target individual characteristics of a person’s tumor. One commonality among all cancer patients, however, is their tendency to become socially isolated after diagnosis. In a preclinical model, OSUCCC – James researchers have shown that “patients” live longer in an environment that provides mental stimulation, physical activity and social interactions compared to an isolated, lonely living situation. Biologically, these “patients” also generate more natural killer (NK) cells, which are part of the body’s immune system and responsible, in part, for the body’s internal fight against cancer; the isolated subjects produced fewer NK cells. In this new study, researchers will further examine whether social isolation hinders the development of the overall NK cells and allows tumors to grow larger, decreasing survival.

Determining the Role of Melanin Variations in Melanoma Formation

Investigator: Emma Crawford of Canton, Ohio, mentored by Christin Burd, PhD, OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program

Melanoma is a cancer that affects the pigment-producing cells in the skin. In this study, researchers will use a preclinical model to evaluate the role of skin pigmentation in BRAF and NRAS gene-mutated melanomas. Previous OSUCCC – James research has shown that a single exposure to ultraviolet light accelerates melanoma formation and contributes to additional mutations in this preclinical model. This study is expected to reveal the role of skin pigments in sun-mediated DNA-damage and spontaneous melanoma formation. This knowledge could help researchers develop preventive methods for populations at risk for melanoma and contribute to overall understanding of how this disease develops.

Predicting Brain Metastases in Breast Cancer Patients

Investigator: Alexander Didier of Lake Zurich, Ill., mentored by Gina Sizemore, PhD, OSUCCC – James Molecular Biology and Cancer Genetics Program, and Bhuvaneswari Ramaswamy, MD, OSUCCC – James Translational Therapeutics Program

Breast cancer is the most common form of cancer in women worldwide, with 10-15% of all deaths due to brain metastasis. The tumor microenvironment is thought to play a key role in tumor metastasis, in which both cancerous and non-cancerous cells exist within and surrounding the tumor. Understanding the interplay of these cells is critical to developing better strategies for treating the disease. In this study, researchers will use human breast cancer cell lines to test whether higher levels of a specific protein (PDGF-B) causes breast cancer cells to grow faster generally as well as specifically in the mammary gland and brain. If this proves true, PDGF-B may serve as a potential predictor of which women will ultimately develop brain metastases. This knowledge could help guide treatment options more effectively, particularly because there are drugs that block PDGF receptors currently available for the treatment of other cancers.

Genetic Mechanisms of Chromosomal Deletions in Cancer

Investigator: Miguel Disbennett of Croton, Ohio, mentored by Ruben Petreaca, PhD, and Jian-Qiu Wu, PhD, both of the OSUCCC – James Molecular Biology and Cancer Genetics Program

Duplication of cellular DNA occurs with each cell division to ensure that the progeny receives a copy of the genome. The process is not always error-proof, and the two strands of the DNA can break. While cellular processes exist to repair these breaks, sometimes these processes fail. When failures occur, genetic changes accumulate that can lead to cellular transformation, a hallmark of cancer. This study focuses on understanding how chromosomal deletions occur. Deletion of entire chromosomal regions can wipe out several genes at once and produce major genomic instability, which has long been observed in cancer cells. Therefore, understanding the mechanisms of these deletions is important for the development of a better cancer model.

Improving Effectiveness of Immunotherapy for Breast Cancer

Investigator: Logan Good of Avon Lake, Ohio, mentored by William Carson, MD, OSUCCC – James Translational Therapeutics Program

Breast cancer is the most common form of cancer in women today and many therapies, including immunotherapy, are available to treat the different subtypes. Only about 12% of breast cancer patients who receive immunotherapy benefit from it. It is thought that certain immunosuppressive cells that exist in breast cancer—known as MDSC—block the effectiveness of immunotherapy drugs. In this study, researchers will evaluate new ways to overcome this challenge so that immunotherapy could potentially be more effective.

Role of Protein Interaction in Cell Division

Investigator: Evie Goodyear of Cincinnati, Ohio, mentored by Jian-Qiu Wu, PhD, OSUCCC – James Molecular Biology and Cancer Genetics Program

Cell division is critical to the proper partitioning of cellular content into two individual cells at the end of the cell cycle. Failures in the cell division process are associated with multiple cancers. To better understand this process, researchers use a specific yeast model with similar cell division components as human cells. This study will analyze the role of specific proteins suspected to play a key role in cellular mechanisms that lead to errors in cell division and cell death. As a result of this work, researchers hope to clarify the mechanism of interaction between Bgs1 and Sbg1 proteins and to clarify how this impacts function in the cell.

NRAS Mutations As a Driver of Melanoma

Investigator: Nickelas Huffman of Canton, Ohio, mentored by Vincenzo Coppola, MD, OSUCCC – James Molecular Biology and Cancer Genetics Program

Previous research suggests that a protein known as RanBP9 is often over-expressed in melanoma patients who have a certain mutation in a gene called NRAS. Researchers believe that RanBP9 serves as a tumor suppressor in melanoma where the NRAS gene is mutated,resulting in slow-growing tumors at the start of tumor growth but in a stable tumor once it becomes larger. This laboratory study seeks to identify the role that RanBP9 plays in NRAS-mutated tumors.

Potential New Biomarker for Early Detection of Pancreatic Cancer

Investigator: Sabrina Kaul of Cincinnati, Ohio, mentored by Zobeida Cruz-Monserrate, PhD, OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program

Pancreatic cancer is one of the leading causes of cancer-related deaths in the United States. Most pancreatic cancers go undetected until they are late-stage and surgery is no longer an option. Early detection and diagnosis tools for this disease, however, do not exist. In this study, researchers evaluate a potential early biomarker for pancreatic cancer called cathepsin E, an enzyme encoded by the CTSE gene). Researchers will look at activity and expression of CTSE in pancreatic cysts to determine if it can be used to identify which cysts are high or low risk for cancer. Researchers will also measure and compare characteristics of cancer cells with high and low expression of CTSE. If a difference in CTSE expression or the addition of a CTSE inhibitor leads to changes in the cancer cell characteristics, it could help detect pancreatic cancer earlier and improve patient outcomes.

Investigating a New Tumor Suppressor

Investigator: Jack Kucinski, mentored by Helen Chamberlin, PhD, Ohio State’s Department of Molecular Genetics, College of Arts and Sciences

Every cell in a single organism has the same DNA, yet there are many cell types. The variation in cells arises because different genes are either active or inactive, and proper regulation is vital. Cancer cells often reverse this process and “turn on” certain genes that promote excessive cell growth and division. In this study, researchers will look at a histone variant, HTZ-1/H2A.z, that has been shown to both activate and repress genes. The study is expected to help scientists understand how this variant behaves as a tumor suppressor.

Understanding Molecular Mechanisms of Chronic Lymphocytic Leukemia

Investigator: Ari On, mentored by Lynne Abruzzo, MD, PhD, OSUCCC – James Leukemia Research Program

Chronic lymphocytic leukemia (CLL) is a cancer of the B lymphocytes in the blood that occurs primarily in older individuals. Some newer treatments have proven very effective but are still vulnerable to acquired treatment resistance. Alternative treatment strategies are needed for when these therapies stop working. In this study, researchers will look at a new approach that targets a pathway called Wnt, which contributes to cancer cell growth by influencing cellular mechanisms that would normally result in these cells being destroyed. In CLL, this pathway is often turned on when it should be off. In this project, investigators propose that a gene called NR1P1 may be an important on/off switch for this pathway. This research is expected to contribute to the knowledge needed to discover therapeutic targets with the potential to circumvent resistance to current frontline treatments.

Stress-induced tRNA intron Accumulation Mechanism of Gene Regulation

Investigator: Lauren Peltier of Vandalia, Ohio, mentored by Anita Hopper, PhD, Ohio State Department of Molecular Genetics

Transfer ribonucleic acids (tRNAs) are molecules in cells that bring amino acids to the ribosome for protein synthesis. All eukaryotic cells contain tRNA introns that must be spliced to generate functional tRNAs. In this study, researchers will investigate whether various environmental stress conditions can lead to the accumulation of tRNA introns in the cell. This would indicate that the sequence remains intact and could serve a specific function.

HER2 as a Target for Certain Invasive Breast Cancers

Investigator: Nikhil Pramod of New Albany, Ohio, mentored by Bhuvaneswari Ramaswamy, MD, OSUCCC – James Translational Therapeutics Program

Invasive lobular carcinoma (ILC) is a form of breast cancer that spreads in spider-like webs, making it more challenging to diagnose on screening mammography. As a result, these cancers often appear in later stages. ILC patients express normal levels of human epidermal growth factor, known as Her2, so existing therapies targeting this growth factor are not effective for patients with ILC. However, studies show that more than 25% of ILC patients carry an altered HER2 gene that leads to higher activation. This suggests that HER2 could still be a potential target for these tumors. HER2 can also become activated following treatment with antiestrogen therapy and lead to resistance or disease progression. Newer small molecule compounds targeting HER2, such as ONT-380 (tucatinib), are being testing in clinical trials for patients with metastatic breast cancer. In this preclinical study, researchers will evaluate whether a two-drug combination that includes tucatinib and tamoxifen, an FDA-approved drug targeting estrogen receptor alpha, can effectively slow tumor growth in this treatment population.

Understanding the Role of Notch in Cancer Cell Communication

Investigator: Grant Stellini of Dublin, Ohio, mentored by Susan Cole, PhD, OSUCCC – James Molecular Biology and Cancer Genetics Program

The Notch cellular pathway is an important part of early cell development that helps determine cell function and facilitate normal cell multiplication. Cancer is a disease that involves unregulated cell growth, and mistakes in the Notch pathway are very common in cancer patients. If developing cells fail to acquire the correct information to determine their eventual purpose, there will likely be an error in the high-level function that normally requires a sum of parts to correctly function. In this study, researchers will examine how modification of the proteins in the Notch pathway influence cellular outcomes. This will enhance researcher understanding of the pathway’s role in cancer development and spread.

Role of Physical Activity on Immune Response in Pancreatic Cancer

Investigator: Olivia Ueltschi of Cincinnati, Ohio, mentored by Zobeida Cruz-Monserrate, PhD, OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program

New research suggests that physical activity may be a promising additional therapy approach that can help boost the immune system to reduce risk for secondary cancers or tumor recurrence. Tumor progression is regulated by interactions between the host, tumor microenvironment and cancer cells. Research has shown that physical activity can regulate the tumor microenvironment and enhance antitumor response by mobilizing major leukocytes into the peripheral circulation. In this study, researchers will look at the role of physical activity in pancreatic cancer to see if it can increase the effectiveness of an immune therapy treatment.

Effects of Voluntary Exercise on Chemotherapy-Induced Anxiety-Like Behaviors

Investigator: Selina Vickery of Savannah, Georgia, mentored by Leah Pyter, PhD, OSUCCC – James Cancer Control Program

As treatment becomes more effective, cancer survivors are a prevalent and growing population. However, cancer survivors and patients often experience negative side effects, such as anxiety, that can last years beyond completion of treatment. Voluntary exercise has been shown to reduce some anxiety in breast cancer survivors. Researchers hypothesize that chemotherapy causes a hyperactive immune system in the brain because chemotherapy activates the immune system. An activated immune-system is also associated with other types of anxiety and can be alleviated by exercise. In this project, researchers will conduct preclinical studies to better understand the specific brain biology underlying the effects of exercise on anxiety behaviors experienced after chemotherapy. This will involve measurement of anxiety-like behaviors, examination of brain tissue and statistical analysis to study brain and immune differences among the different study populations.

Characterizing the Role of the OLFM4 Gene in Cholangiocarcinoma

Investigator: Maxwell Wilberding, of Middleton, Ohio, mentored by Sameek Roychowdhury, MD, PhD, OSUCCC – James Translational Therapeutics Program

Cholangiocarcinoma is rarely operable and has few viable medical treatment options. Ultimately, most patients develop resistance to therapy shortly after treatment. Recent studies have shown that the human olfactomedin 4 (OLFM4) gene is activated at different levels in cancer tumor cells compared to normal cells. This gene forms proteins that help the body’s cells clump together and form tumors. In this study, researchers will use human tumor tissue samples to assess differences in the OLFM4 gene before and after a patient is treated. They will also study cell progression in a cell culture model. The ultimate goal is to gain knowledge that will help guide development of new therapies.

Visualizing Mismatch Repair in Real-Time, Live Cells

Investigator: Tiffany Yu of Mason, Ohio, mentored by Richard Fishel, PhD, OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program

The machinery that copies DNA is good—but not perfect—and makes about 6,000 mistakes every time it copies the human genome. These mistakes create “mismatches” in the DNA that are fixed by mismatch repair. About 2% of humans carry a mutation in one of the core mismatch repair genes that predispose people to early onset colorectal, endometrial, ovarian, gastric or upper urinary tract cancer. This mutation is known as Lynch syndrome. In this study, researchers will develop imaging technology that allows for real-time visualization of the function of individual or interacting molecules. This could help scientists better understand the function of proteins and single molecules in live cells. This proposal is highly innovative since this is a first in developing the step-wise cellular single molecule imaging methodology for mismatch repair, which has been linked to cancer and therapeutic drug resistance.

Understanding Biology of Alternating Electric-Field Therapy on Breast Cancer Cells

Investigator: Meihui (Mia) Zhang of Sakado, Japan, mentored by Jonathan Song, PhD, OSUCCC – James Molecular Biology and Cancer Genetics Program

Breast cancer remains a leading cause of cancer-related deaths in the United States among women, primarily due to metastasis (spreading to other parts of the body). Triple-negative breast cancer is a highly metastatic and aggressive form of the disease with limited effective long-term treatment strategies. More effective, noninvasive treatment options are critically needed for this disease. In this study, researchers will investigate the effects of externally applied alternating electric fields in the treatment of triple-negative breast cancer. This study could enhance scientific understanding of a new noninvasive treatment modality that could expand its role in patient care.

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About the OSUCCC – James
The OSUCCC – James strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 51 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program’s 356-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet® designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors and with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. For more information, visit cancer.osu.edu.

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