Grant Archive - Page 51 of 138

Michael Kastan, M.D., Ph.D.

The Duke Cancer Institute and the College of Veterinary Medicine at N.C. State University formed a Comparative Oncology Consortium (COC), taking advantage of their expertise and national leadership in their respective disciplines and their geographic proximity. The goals are to collaborate in pre-clinical and clinical cancer research activities in order to advance our understanding of both cancer causation (a high incidence of specific cancers in specific dog breeds provides opportunities to identify new cancer susceptibility genes and environmental factors in cancer causation) and of behaviors and genetics of specific tumor types, as well as to coordinate clinical trials in humans and canines so that novel therapies can be tested in both settings, with information gained in one setting informing the other. In addition to response outcomes of these cancer therapies, the ability to use biomarkers and pharmacology in the canine models can be a novel addition to the characterization of these new cancer therapies and these insights could result in significant enhancements of clinical trial designs (including dosing, scheduling, and combination therapies) when these treatments are tested in human clinical trials. Cost savings and improved clinical trials design would help encourage pharmaceutical companies to use the canine models as part of the assessment process and would benefit the canine patients by giving them access to these novel therapies.

Baoli Hu, Ph.D.

Funded in partnership with WWE in honor of Connor’s Cure

Medulloblastoma is the most common malignant brain tumor in children. There are four distinct forms of this tumor based on its gene profiles, and a form known as Group 3 medulloblastoma is the most aggressive and deadly, which accounts for 25%-30% of all medulloblastoma. Each medulloblastoma group has distinct abnormal gene expression that determines how it creates, grows, and spreads tumors. Changes in gene behavior, like overexpression or underexpression, are controlled by what is called epigenetics. Fortunately, we know how to manipulate epigenetics with drugs. Dr. Hu and his colleagues found two epigenetic components that play important roles in controlling gene expression in tumor. Interestingly, these two epigenetic components seem to work together: when one component is suppressed, the other increases, and vice versa. A gene called MYC is very active in many cancers including Group 3 medulloblastoma. In this project, Dr. Hu’s team will characterize these two epigenetic components to understand more precisely how they work, particular in controlling MYC expression, even further, they will test in the lab whether “drugging” these epigenetic factors can halt the growth and spread of medulloblastoma tumors. If this hypothesis is proven, it may be possible to use these drugs in combination to treat this devastating childhood cancer.

Pavani Chalasani, M.D.

Funded by Hooters of America, LLC

The goal of “Campaign to Improve Access to Clinical Trials” at The University of Arizona Cancer Center (UACC) is to increase the clinical trial access to a diverse population in Arizona. Dr. Pavani Chalasani, Breast Cancer Disease Oriented Team Leader, will oversee the campaign to improves access by involving the breast multidisciplinary team, patient navigators and physician liaisons to develop educational materials and outreach programs. Patients and community physicians will be targeted through proposed outreach programs by developing targeted educational materials. Materials and training will be provided to introduce and educate about clinical trials to patients early by various members of their cancer team. The goal of this campaign is to become a model for other disease teams and cancer centers to implement to improve clinical trial enrollment.

Jianjun Zhao, M.D., Ph.D.

Multiple myeloma is a cancer of the blood and is the second most frequently diagnosed blood cancer in the US. Every year, about 30,000 patients are newly diagnosed, and about 12,000 die from this cancer. The main symptoms include anemia, bone pain, kidney failure, and infections. The most recent treatments have improved patient survival from about 3.5 to 5 years. Unlike some other blood cancers, myeloma still cannot be cured. Thus, the development of new drugs and treatments is essential. The purpose of our study is to understand how an understudied class of genes, called long noncoding RNA genes (lncRNAs), participates in the development of multiple myeloma and may be used to develop entirely new treatments. Specifically, we propose innovative approaches to investigate a specific lncRNA gene, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and how it functions in the repair of damaged DNA to promote the initiation and progression of multiple myeloma. We recently discovered that the MALAT1 gene is involved in an alternative DNA repair network that has seldom been studied in multiple myeloma. We believe that MALAT1 modulates the transition to advanced myeloma and myleoma that occurs outside the bone marrow. Our fundamental goal is to establish how MALAT1 regulates the repair of DNA damage and therefore its functional significance in multiple myeloma initiation and progression. This entirely novel knowledge will open new avenues for patient therapy and ultimately improve patient outcomes.

Jamie Spangler, Ph.D.

Funded by the Constellation Gold Network Distributors

Only a limited number of proteins are found in nature, and many of them have multiple different functions that clash with one another, which makes them poor drugs. There is a growing interest in engineering existing proteins or designing brand new proteins that are better than the ones in nature. Most current methods for protein design use a random approach. However, as our understanding of protein structure improves, we have an exciting chance to use structure to guide design. My lab applies new tools from biology and engineering to figure out the mechanisms that control protein behavior. We then use this information to discover and develop better drugs.

One of the biggest cancer breakthroughs is immunotherapy, which activates the patient’s own immune system to fight disease. My lab aims to bias the activity of immune proteins in order to achieve a targeted response against cancer. For more than twenty years, immune proteins such as cytokines and antibodies have served as powerful weapons in cancer treatment, but they are limited by issues such as drug resistance and harmful side effects. As a result, there is an unmet need to create new proteins that overcome these challenges. Building on our lab’s insights and platforms we have designed, we will make a new protein drugs that act through unique pathways to induce potent anti-cancer immune responses.

Adam Shlien, Ph.D.

Funded by the Dick Vitale Gala in memory of Chad Carr

Cancer is the leading cause of disease-related death of children past infancy in North America. All cancers contain mutations in their DNA, but the causes of these mutations are usually not known. This gap in our knowledge negatively impacts patient care: It is difficult to predict how a tumor will change – how it will respond and whether it will come back – if one does not understand why or how it developed in the first place. Recently, our lab and others have shown that some childhood cancers contain a fingerprint which can be used to pinpoint what caused its mutations and when they developed. The identification of these fingerprints, or mutational signatures, is a rapidly evolving area of research that has benefited from new technologies, such as whole genome sequencing. This project will identify mutational signatures in aggressive childhood cancers. We will seek to understand whether cancer- causing mutations have common fingerprints, and if these can be used to select patients that would benefit from ongoing clinical trials.

Lewis Shi, M.D., Ph.D.

Volunteer Grant funded by the 2018 V Foundation Wine Celebration in honor of John and Biserka Noval

Cancer is a leading global health concern. Until recently, cancer patients are normally treated with surgery, pharmaceutical reagents that can kill tumor cells (chemotherapy), and radiation (radiotherapy). In recent years, scientists and doctors have been trying to improve patients’ own immune function to combat cancer, known as immunotherapy. Cancer cells can fool the immune system by expressing some markers that can inhibit immune function. These markers are called “immune checkpoints”, including CTLA-4 and PD-1. Subsequently, blocking “immune checkpoints” with reagents (anti-CTLA-4 and anti-PD-1) could enhance immune function and result in impressive curative effects in some patients with cancer. Yet, a lot of patients do not respond to anti-CTLA-4 and anti-PD-1. In order to broaden the patient populations that can benefit from these novel reagents, we plan to change the metabolic features of the microenvironment that tumor cells live in. We hope doing this will improve the function of immune cells, which then causes non-responsive tumors to respond to anti-CTLA-4 and anti-PD-1 treatment. Our studies might also identify some markers that can help doctors in selecting the right patients for these therapies. Our long-term goal is to translate our findings from bench to bedside by designing clinical trials to test combination therapies, particularly in cancer patients that have been non-responsive to anti-CTLA-4 and anti-PD-1 therapies.

Paz Polak, Ph.D.

Vintner Grant funded by the 2018 V Foundation Wine Celebration in honor of Gina Gallo

One of the deadliest cancers is called Triple Negative Breast Cancer (TNBC). Women with TNBC are more likely to die of breast cancer than women with other types of breast cancer. This type of cancer is more common in African American women.

Treatments for TNBC exist, but we do not know if they are equally effective for all women with TNBC. One reason the outcome might be poorer for African American women is because the standard treatments might be less effective for them. Treatments for TNBC work better when a woman has a certain mutation in gene called BRCA1 and related genes known as RAD51 genes. Unfortunately, this treatment may not work if the gene has been turned off by a mechanism called methylation. This process of methylation is much more common in African American women. In this proposal, we want to find out how frequent methylation of BRCA1 and RAD51 genes occurs in Caribbean populations and then compare the response to TNBC treatment for African American, Caribbean American and European American populations. We hope to find how frequently BRCA1 gene is turned off in breast cancer patients of Caribbean origins and then use this knowledge to assist in the choice of targeted therapy for these patient populations.

Mary Philip, M.D., Ph.D.

Primary liver cancer is a leading cause of cancer death worldwide. Liver cancers are resistant to many cancer drugs. Our immune system has enormous power to find and destroy infectious microorganisms in our bodies, and scientists reasoned that immune cells such as T cells could also find and destroy cancer cells. Using a mouse model of liver cancer, we found that T cells could recognize cancer cells in the liver, however the T cells failed to kill the cancer cells. We discovered that interactions between liver cancer cells and T cells quickly restructured T cells’ DNA. DNA is the program that controls how cells respond and function. The DNA restructuring in T cells took away the T cells’ ability to kill cancer cells. Our goal is to understand how the interaction between liver cancer cells and T cells makes T cells dysfunctional. We are working to develop a three-dimensional liver cancer model in cell culture dishes. We can add T cells to precisely study the earliest changes in T cells after they encounter a liver cancer cell. This will give us clues about why the T cells are shut down their anti-tumor function. We will then test DNA targeting strategies to see if they prevent T cells from becoming dysfunctional. Ultimately, these genetic targeting strategies can be used to activate T cell responses against cancer cells in patients with liver cancer.

Selma Masri, Ph.D.

Funded in memory of Bob Moonan

Of the cancers that affect both men and women, colon cancer is the second leading cause of cancer deaths and the third most commonly diagnosed cancer in the United States. Interestingly, evidence from the clinic links disruption of normal 24-hour rhythms with many diseases including a higher risk of cancer. Our internal clock controls sleep/wake cycles, feeding and metabolism and disruption of the clock has been reported in several cancer types, including colon cancer. Yet, the precise process of clock disruption in colon cancer remains undefined. We are interested in cells that have the ability to initiate tumors because these cells have been found to be treatment resistant. We propose to determine how loss of the clock can promote colon cancer by changing the cues that direct these cells that initiate cancer. To accomplish this, we have generated a mouse model to understand the effects of clock disruption on cell growth in the intestine. We propose that disruption of both the clock and loss of cues that control normal cells in the intestine can result in colon cancer. The goal of these studies is to provide new directions towards clock-dependent treatments that can target colon cancer.