Designed to identify, retain and further the careers of talented young investigators. Provides funds directly to scientists developing their own independent laboratory research projects. These grants enable talented young scientists to establish their laboratories and gain a competitive edge necessary to earn additional funding from other sources. The V Scholars determine how to best use the funds in their research projects. The grants are $200,000, two-year commitments.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND WITH SUPPORT FROM BRISTOL MYERS SQUIBB
Heart disease and low blood counts are common complications for men with prostate cancer. There are some reasons why this might happen that are already known – either because of the cancer itself or because of some of the treatments for cancer. Recently, scientists have found that white blood cell clones (cells that all come from one cell; called CHIP) have changes in their DNA that might put people at higher risk for heart disease, complications with blood counts, and death. CHIP, like prostate cancer, is associated with age, and may be contributing to heart disease and blood count problems we see in men with prostate cancer. This study will look to see if men who have CHIP with prostate cancer have worse outcomes and if new treatments for prostate cancer contribute to CHIP.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND WITH SUPPORT FROM BRISTOL MYERS SQUIBB
Lung cancer is the leading cause of cancer deaths in the United States. Non-small cell lungcancer (NSCLC) accounts for the majority of lung cancer diagnoses and has a very low survivalrate. There is a sub-population of cells within NSCLC tumors called cancer stem cells (CSCs)that are highly aggressive. These CSCs are capable of fueling the growth and metastasis oftumors and have been shown to be resistant to current drug treatments for NSCLC. Therefore,CSCs must be eliminated to effectively treat and gain lasting remission in patients with NSCLC.CSCs can communicate with other cells in a tumor by transferring information packaged withinsmall particles called extracellular vesicles (EVs). We hypothesize that the molecules packagedwithin EVs from CSCs can make non-CSCs within NSCLC tumors more aggressive by increasing their ability to grow and metastasize. We propose to identify the molecules packaged within NSCLC CSC EVs. We also aim to block the function of the molecules within the CSC EVs to prevent the growth of NSCLC cancer cells. Completion of these studies will provide newinformation about how CSCs function to make NSCLC deadly. In addition, these studies will help in the design of new strategies to eliminate NSCLC CSCs which may provide effective, long-term treatment for NSCLC patients.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND WITH SUPPORT FROM BRISTOL MYERS SQUIBB
Immune cell-based therapies represent the latest pillar of cancer therapy. Chimeric antigen receptor (CAR)-T cells have demonstrated significant anti-tumor activity against B cell leukemia and lymphoma and similar efficacies against multiple myeloma. CAR-NK cells are a newer addition to the cellular immunotherapy field but have already shown impressive results in the treatment of lymphoma. In this project, we will evaluate the activity of CAR-T and CAR-NK cell therapies targeting BCMA and TnMUC1 as single agents and combination strategies for the treatment of multiple myeloma. In addition, we will develop methods to enhance the efficacy and persistence of NK-cell based therapies through strategies to overcome immunosuppression. Successful completion of this project would generate novel and enhanced therapeutic strategies to treat multiple myeloma with immune cell-based therapies.
Funded by the Constellation Gold Network Distributors in honor of the Dick Vitale Fund
Scientists have given immune cells a detector forB-cell acute lymphoblastic leukemia (ALL).Theycalled these cells CAR T cells. In some patients, these CAR T cells disappear before they can clear the tumor. In others, these cells become too exhausted to work. We have recently identified the molecular code that prevents T cells from dying off or becoming exhausted. With the funding support, we will use this molecular code to make CAR T cells stay in cancer patients longer and clear B-cell ALL more effectively.We hope to use this strategyto cure a much larger population of pediatric cancer patients with B-cell ALL.
Funded by the Constellation Gold Network Distributors
Patients with pancreatic cancer are usually diagnosed with advanced disease and suffer from a very poor prognosis with limited treatment options. This is due to the lack of early detection tests and the largely asymptomatic onset of the disease. In the past decade, drugs that pit the body’s immune response against cancerous cells—also known as immunotherapeutics—have been used to treat a variety of cancers but seem to only benefit a limited number of patients. In particular, immunotherapeutics seem generally ineffectiveagainst pancreatic cancer, although it is unknown if there is a subset of pancreatic cancer patients who may benefit from this therapeutic approach. To understand why, we will use a new platform developed in our laboratory to study how different populations of cancerous and immune cells within the tumor interact with each otheras well as with the other cells in the tumor’s surroundings (i.e. tumor microenvironment). Additionally, the platform will track how these interactions change when the tumor is exposed to disturbances such as immunotherapeutics. Our study will allow usto understand how individual cell populations contribute to the pancreatic tumor’s response—or lack thereof—to immunotherapeutics as well as its ability to evade the immune response.Ultimately, our findings can be used to develop tests that can predict whether a patient with pancreatic cancer will benefit from a certain immunotherapeutic approach.
Funded by Mark and Cindy Pentecost in memory of Will DeGregorio
Ewing sarcoma relies on decades-old chemotherapy options, where aggressive treatments are met with poor disease outcomes. Ewing sarcoma is a devastating disease that affects mostly young adults age 10-16, but children under the age 10 can also develop this deadly illness. Due to the disease’s classification as a rare disease (less than 10,000 cases/year), it has not received the attention of the research community like other more common cancers; therefore, it is in desperate need of intense research and development of new therapeutic options. One of the key observations of Ewing sarcoma made back in the 1930’s is the accumulation of large amount of glycogen. Glycogen is a sugar molecule that our body uses to store energy; only specific organs such as the liver and muscle are capable of producing glycogen. The ability of Ewing sarcoma tumors to store large amount of glycogen has been forgotten until now. This proposal aims to understand the reason behind large glycogen accumulation in Ewing sarcoma and exploit the glycogen deposits as a possible drug target for the treatment of Ewing sarcoma.Dr. Sun has established ongoing collaborations with pediatric physicians to study the basis of glycogen targeting agents for the treatment of Ewing’s sarcoma, and to define early diagnostic biomarkersand evaluation of response to therapy.The long-term goal is to establish treatment options using one or multiple modalities as tailored therapies against Ewing’s sarcoma’s metabolic vulnerability.
Volunteer Grant funded by the V Foundation Wine Celebration in honor of Robert and Gail Sims
The advent of immunotherapy has dramatically changed the landscape of cancer treatments. The power of immunotherapy its potential toinduce long-lasting benefits for terminally ill patients, however only a minority of patients are currently responding to the treatment. We have previously shown that the composition of the immune cells found within the tumor is critically important for the therapeutic outcome, with two immune cell types being required for a strong and effective tumor elimination. These cell types are so-called killer T-cells, which recognize and eliminate tumor cells and dendritic cells, which are needed to “license” T cells to kill.
Killer T-cells are most effective when they are directed against targets only present on tumor cells and when all tumor cells have an evenly distributed expression of this target. However, in most tumors the targets are unevenly represented and only partially present representing ahurdle for successful tumor cell elimination. But more importantly this diffuse pattern directly weakens the strength of the killer T-cellresponse and changes the composition of immune cells in the tumor. To date we do not understand why a weaker T-cell response is observed and how we could overcome this shortcoming therapeutically. In the funded study, we aim to understand the dynamics of akiller T-cell responses against tumors with uneven target expression. In doing so we aim to understand which factors impact the expansion and function of killer T-cells and ultimately harness this knowledge to expand the fraction of patients benefiting from immunotherapy.
Funded through the Stuart Scott Memorial Cancer Research Fund by the Ayodele family in memory of Ade Ayodele
Colorectal cancer (CRC) is preventable when detected early. Because of effective screening, fewer Americans aged 50 and older are now being diagnosed with CRC or dying from it. Over the past 20 years, however, the number of Americans under age 50 who are diagnosed with CRC has doubled. Health experts estimate that the numbers of younger Americans with CRC will continue to increase rapidly over the next 10 years. The reasons for this increase are poorly understood. In addition, younger people are less likely to be diagnosed with CRC when the disease is still at an early stage. Also, of concern is that among men and women of all ages and all races, African-American men are the most likely to die of CRC.
The goal of this study is to better understand the reasons why people under age 50 in Utah are being diagnosed with CRC. As a first step, the researchers plan to identify the specific places in Utah where diagnoses of CRC among younger people are increasing the most. Next, they plan to conduct 1-hour recorded Zoom interviews over phone and/or video with 20 people who live in these places and were diagnosed with CRC when they were under age 50. Thirdly, the researchers plan to create and test a program that will raise Utahns’ awareness of the increasing risk of CRC among residents of the state who are aged under 50. This study is unique as CRC survivors are key to helping drive the study forward.
Funded through the Stuart Scott Memorial Cancer Research Fund by the Marks Family in honor of Lisa Curtis
The human body is estimated to remove over a billion cells every day, a process achieved by a relatively rare population of cells called phagocytes. When a phagocyte ingests a dying cell, it essentially doubles its content (analogous to a neighbor moving into your house). Yet, phagocytes such as macrophages often ingest multiple targets in quick succession. How these phagocytes maintain their homeostasis and manage the excess influx of dead cell cargo, are interesting scientific problems that are largely unexplored. This is an important topic in understanding cancer development broadly, and the development of cancer therapies specifically, because the clearance of cancer cells directly establishes an environment for the tumor to grow. Exciting avenues of therapy involve trying to either break down this tumor-promoting environment or by increasing the immune response against the tumor. These approaches show much promise; however, they often only work in specific patient populations. We believe that to develop a more effective therapy, we must understand the underlying processes that link clearance of cancer cells to generating an anti-cancer immune response. To this end, my lab focuses on studying phagocytes that are prevalent in Triple-Negative Breast Cancer (TNBC), how tumor cell clearance contributes to TNBC progression, and discovering new ways to target these cells to treat TNBC.
Funded by the Constellation Gold Network Distributors
Non-Hodgkin Lymphomas are common cancers which can be cured in some patients by combinations of multiple chemotherapy drugs. Currently, these treatments consist of giving many drugs at the same time, waiting some weeks to recover from side effects, and repeating the cycle several times. We have discovered that in the most common combination therapy for Non-Hodgkin Lymphomas, while the use of many chemotherapies kills more cancer cells, the drugs do not enhance one another’s activity. Instead, certain drug pairs interfere with one another’s effects. This suggests that treatment might be more effective at killing cancer cells, and cure more patients, if this interference were avoided. This could be accomplished by giving certain chemotherapies at different times from each other. We will study a few lymphomas and measure how chemotherapies interact to determine which should or should not be given at the same time. A computer model will simulate how tumors respond to combinations of drugs given at various times. This simulation will use measured drug interactions to predict which treatment designs will be most effective at killing cancer cells. We will test these treatments on human lymphoma cells, and compare them to the current ‘all-drugs-at-once’ strategy. If this research finds a more effective approach to treatment, it can next be tested in animals, and eventually in human clinical trials. Ultimately we hope to identify a simple change in the use of already approved medicines that has the potential to cure more cases oflymphoma.
