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.
Acute Myeloid Leukemia (AML) is the most common and deadliest blood cancer in adults. In 2022, over 11,000 AML patients sadly lost their lives in the USA. The treatment options for AML have stayed the same for many years. But in 2018, a new oral medication called Venetoclax was introduced as a potential breakthrough for AML treatment.
Normally, when our cells become damaged, they have a way of self-destructing called apoptosis. It helps stop any defects from spreading in our bodies. Unfortunately, cancer cells, including those in AML, don’t follow this program and become “immortal,” spreading and causing trouble. Venetoclax is designed to make those cancer cells self-destruct, specifically targeting and killing them.
At first, AML patients showed promising responses to Venetoclax. However, it’s disheartening that about 3 out of 10 patients don’t respond to the medication and in many other patients, AML comes back after treatment. That’s where our research comes in. We want to understand why some patients don’t respond to Venetoclax and how leukemia cells manage to escape apoptosis triggered by the medication.
Through our studies focusing on the molecular aspects of resistance to Venetoclax, we aim to identify potential targets for new and improved therapies for AML. Our studies will also propose combination treatments that could enhance the effectiveness of Venetoclax. Ultimately, with the knowledge gained from this research, we aspire to lay the groundwork for future clinical trials and develop better and safer treatments that will help AML patients live longer and have better lives.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Diffuse midline glioma (DMG) is a fatal pediatric brain tumor, striking 200-400 children in the U.S. each year. Most children with DMG survive <1 year and have no proven therapies beyond radiation. A series of new drugs are being tested in clinical trials of DMG patients, but we lack sufficient tools to track how well they work. Cancer is a rapidly moving target as it can mutate to evade the onslaught of anti-cancer drugs; thus, tumors must be analyzed repeatedly during treatment to assess therapy response. Today’s standard of care for DMG is limited to frequent imaging (MRI), which provides insufficient data to assess therapeutic response. By advancing a new blood-based assay specific to DMG, we aim to dramatically improve our ability to track the effects of treatment on this devastating disease. We will exploit extracellular vesicles (EVs) — small “bubbles” shed by cells — as surrogate markers of therapy response in DMG patients. EVs contain molecular contents (e.g., protein, RNA, DNA) from their mother cells. Tumors shed large quantities of EVs into the bloodstream, offering a potential new way to monitor treatment in DMG patients. We will develop a new assay platform that integrates cutting-edge developments in materials, optics, and deep learning AI into a single system for efficient EV analysis and test whether our platform reliably predicts drug response in DMG patients. Our approach has the potential to transform DMG therapeutic trials and clinical practice, and its flexibility may lend itself to other types of pediatric and adult cancers.
Funded by the Dick Vitale Pediatric Cancer Research Fund in honor of Beau Christensen
Primary brain tumors are the most common solid tumors in children. They are also the most frequent cause of cancer-related death in children and teens. Genetic profiling is an important tool in the treatment of these tumors. DNA sequencing provides information for proper diagnosis. It can also be used to understand how tumors change over time and to monitor response to treatment. However, performing biopsies is very challenging for brain tumors. Many tumors are in important areas of the brain and can’t be fully removed or repeatedly sampled.
“Liquid biopsy” is a new tool that can be used to diagnose cancer and track response for some systemic tumors. It works by detecting small pieces of DNA that break off from tumors. These can be found in the cerebrospinal fluid (CSF) and in blood (circulating tumor DNA, ctDNA). Accessing these “liquids” is usually easier and has fewer complications than surgery.
We previously showed that CSF ctDNA can be used to diagnose brain tumors and that ctDNA is associated with active disease. But there are instances where CSF ctDNA is not informative due to technical limitations. We propose to improve how these samples are analyzed so CSF liquid biopsies can help more patients. Our prior work was retrospective. For this project, CSF ctDNA monitoring will be added to a clinical trial. We will investigate whether there is a relationship between CSF ctDNA and disease burden. Validating CSF liquid biopsy could greatly improve how pediatric primary brain tumors are diagnosed and treated.
Funded by Friends and Family of Loie Conrad and Stacey Sanders
CAR-T cells are a new therapy where a patient’s own white blood cells are isolated, modified in a dish to better recognize their tumor, and infused back in. These engineered T cells have transformed the treatment of blood cancers and are being actively considered for solid tumors such as triple-negative breast cancer (TNBC) and ovarian cancer. Unfortunately, CAR-T cell treatment success has been limited partly because these cells eventually lose their ability to control tumors in a process called T cell exhaustion. Understanding why CAR-T cells become exhausted in solid tumors is absolutely required to improve patient outcomes and get better immune-targeted treatment responses. These dysfunctional T cells show many defects, including overproduction of a receptor known as PD-1 that inhibits T cells. It is not currently known why high levels of PD-1 are found on exhausted CAR-T cells and what the consequences of high PD-1 expression are. We hypothesize that by focusing on exhaustion-specific regulation, we can rewire CAR-T cells to prevent PD-1 mediated dysfunction in tumors while minimizing side-effects. These will be attractive targets for translation to early-phase CAR-T clinical trials in breast cancer, ovarian cancer, and other solid tumors, where there is intense interest in reducing T cell exhaustion.
Funded by Constellation Gold Network Distributors in honor of the Stuart Scott Memorial Cancer Research Fund
Humans are genetically diverse and exhibit variable susceptibility to developing diseases with a strong genetic component, leading to significant health disparities. The mechanisms by which certain genetic alterations differentially impact disease development and progression depending on the genetic background and the type of genetic lesion remain poorly understood. To tackle these problems, my group has developed sophisticated methods to rapidly engineer and probe endogenous gene function in primary cells and tissues of living animals in a manner that is agnostic to an individual’s genetic background. My lab is using these methods to elucidate the specific ways that different genetic alterations influence cancer development, progression, and therapy responses, with the goal of using this knowledge to better diagnose and devise novel strategies to target cancers in a more precise, personalized manner.
Funded by the Stuart Scott Memorial Cancer Research Fund
Adult midline gliomas are aggressive, unresectable tumors for which no curative treatments exist. These tumors are caused by faulty ‘epigenetics’ i.e. problems in the way cells switch certain genes ‘on’ or ‘off’. Our research is studying a protein complex called PRC1, which we have found these tumors use to keep certain genes switched off to promote growth. We aim to understand how PRC1 functions so that we can devise novel ways to target this pathway and develop new treatments for this disease.
New cancer drugs are needed to improve quality of care, deliver cures, extend life and prevent relapse. We need to hunt in new places or in places that are not yet fully explored to come up with ideas for better drugs. We have focused on a previously overlooked area that is prime for exploitation, namely how DNA is packaged into cancer cells. DNA is the instruction manual of the cell and must be copied forward when cancer cells divide, a process called DNA replication. However, because DNA is so long it must be packaged correctly into the cell nucleus after it is copied. The cell makes a large number of DNA-packing proteins called histones to accomplish this task. We aim to find ways to attack a cancer cell’s ability to make histone proteins as a new cancer treatment strategy. We expect this be safer (less toxic) than targeting DNA replication itself, and hope to find ways to target it specifically to cancer cells. To do this, we are focused on the details of the DNA packing problem, by digging into the cellular components that control this process and asking molecular questions using the latest technologies. We want to understand how this process works better and how it goes awry in cancer cells so that we can exploit our findings for new drugs.
In the past decade, the incidence of pediatric IBD has doubled, and that of early-onset CRC has quadrupled in the United States. The aggressive clinical course of IBD and reduced overall survival of associated young-onset CRC represent an unmet clinical need. Notably, although the reasons for the upward trend of childhood IBD and early-onset CRC are poorly understood, food and nutrition that raises blood sugar have been identified as the major risk factor. Our research takes the nutrigenomic approach to investigate food-gene regulatory networks that can be exploited for harnessing tumor-initiating cells and pro-tumor inflammation. We anticipate that new mechanistic links and therapeutic targets identified in this study will inspire novel preventive and curative strategies to combat inflammatory diseases and cancer.
My research focuses on a class of proteins called chemokine receptors. Many types of cancers will express these receptors, and this can contribute to cancer metastasis. While many drugs have been developed to block chemokine receptors, very few of these drugs have been effective in clinical trials. This is largely because these drugs must hold these proteins in an “off” position 100% of the time to be effective, which is a tall order. We propose to develop a new class of drugs that turn on pathways in cells that will degrade these chemokine receptors—making them “disappear” from cells entirely. We anticipate that this will be a more effective way to prevent these proteins from promoting metastasis than previous drugs that just try to keep chemokine receptors from being turned “on.” This proposal is early stage validation of a new strategy to drug chemokine receptors. However, in the long term, we hope that this work will ultimately improve cancer treatments in two ways. First, it could inspire both new classes of drugs that will block cancer metastasis. Second, it could provide new strategies to discover drugs with these unique properties.
Therapies that recruit and reactivate a patient’s own immune system against cancer have shown a great deal of promise. However, not all patients benefit from these therapies. Thus, developing strategies to boost immune-based treatments is critical. One approach is to develop drugs that improve the function of immune cells. This can be done by targeting transcription factors, which are proteins that help regulate the expression of other proteins. However, transcription factors are very difficult to drug because they often do not have suitable binding sites for chemical compounds. Nevertheless, we recently developed compounds that target a transcription factor known to be important in certain immune cells. Our major goal is to see if targeting this transcription factor can boost the immune response against tumors in mice. We will also try to understand how these compounds reprogram immune cells. This is important because several companies are developing similar drugs, but how these drugs work is not fully understood. The experiments in this proposal will shed light on how this class of drugs work. This will be useful for evaluating how they are used in patients to improve patient outcomes like increased survival.
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