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.
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.
There are many types of kidney cancer and most current treatments were designed for the commonest type, called “clear-cell kidney cancer.” However, these therapies work less well in other types of kidney cancer. Unfortunately, because the different kinds of kidney cancer can look similar under the microscope, many kidney cancers are misdiagnosed.
One such cancer is “translocation renal cell carcinoma” (tRCC), which makes up about 5% of all kidney cancers in adults and over half of kidney cancers in children. Early and accurate diagnosis of tRCC is important for two reasons. First, this kidney cancer has a poor prognosis and it is vital that patients are accurately informed of their diagnosis. Moreover, an early diagnosis may give a patient the opportunity to cure the cancer through surgery before it spreads. Second, an accurate diagnosis can inform which is the best treatment for a patient to receive.
Although tRCC is frequently misdiagnosed under the microscope, it is unique in terms of the genes it expresses. In this project, we will develop methods to diagnose tRCC based on its distinctive pattern of gene expression. We will apply these methods to both biopsies of tumor tissue and so-called “liquid biopsies,” in which DNA from tumor cells is extracted from a routine blood draw. This work will advance the accuracy and ease with which kidney cancer is diagnosed and may lead to new ways to diagnose tRCC earlier – when it can be caught and cured before it spreads.
The immune system provides critical protection against cancer. In fact, new patient therapies designed to boost immune defenses (immunotherapies) have greatly improved cancer treatment. T-cells are a key component of the immune system that can protect against tumor growth. Notably, T-cells can be harnessed for use in cancer therapies in the form of ‘adoptive cell therapy’ (ACT). ACT is an exciting approach in which T-cells are administered to a patient to help fight cancer. Encouragingly, ACTs have successfully cured certain cancer types.
However, ACT does not work well for most cancers. In our work supported by the V Foundation, we will test new strategies to improve ACTs against pancreatic cancer, one of the most lethal cancer types. Completion of this project will yield two important outcomes: 1) Increase our understanding of how the immune system fails to control cancer, and 2) Provide important insight into enhancing the effectiveness of ACT in patients with pancreatic cancer. Immune-based therapies offer hope and promise to cancer patients were traditional treatment approaches (such as chemotherapy or surgery) have failed. This project funded by the V Scholar Program explores new opportunities to enhance cancer immunotherapies.
Vintner Grant funded by the V Foundation Wine Celebration in honor of Leslie Rudd and Family
Cancer is one of the leading causes of death across the globe. Early cancer detection can facilitate effective treatment and fewer side effects to improve patient survival and quality of life. Therefore, there is tremendous interest in using recent technological advances in DNA sequencing, medical imaging, and machine learning methods to enable early detection efforts in cancer. Early detection efforts are likely most effective among individuals genetically predisposed to cancer. Moreover, DNA mutations during the aging process can also increase the risk of developing cancer. Therefore, we aim to use population-level sequencing data to build computational methods to assess individualized risk for developing cancer. We envision that the proposed approach will provide novel insights into the role of inherited and acquired DNA mutations toward tumor growth in high-risk individuals. These insights can be employed to facilitate early detection efforts in cancer.
More than 70% of adults in the USA are obese or overweight. Obesity is a known risk factor for 13 types of cancer. This includes postmenopausal breast cancer. Breast cancer is the second most common cancer among women in the USA. It affects 1 in 8 women and leads to more than 40,000 deaths a year. Obesity is associated with a 30-50% increase in breast cancer incidence.
The expanded fat pad in obese patients surrounds breast cancer cells and supports cancer growth. However, we do not yet understand how the presence of breast cancer cells changes the surrounding fat pad, and how this, in turn, supports cancer growth. We propose that there is a reciprocal cross-talk between breast cancer cells and the cells of the surrounding fat pad, and that breast cancer cells secrete factors to generate tumor-supporting cells.
Our goal is to identify these secreted factors using functional studies and mass spectrometry approaches. We will investigate the underlying mechanism of how these factors change the fat pad. Finally, we will determine the functional importance of these changes to breast cancer cell growth. We envision that our discoveries will have a major impact on obese and overweight women at elevated risk of breast cancer. In the immediate future, our discoveries highlighting the dangerous cross-talk between breast cancer cells and the surrounding obese fat pad could lead to dietary interventions and weight-loss counseling. Long-term, we are excited by the possibility that our discoveries will lead to novel screening and therapeutic strategies.
Funded by the Stuart Scott Memorial Cancer Research Fund and the V Foundation Wine Celebration for Julie Maples, in honor of Antrese Rose Allegro
Breast cancer is one of the most diagnosed cancers in women and it is the top cause of cancer death in Black and Hispanic women. While great advances have been made in the detection and treatment of breast cancers, certain forms of breast cancer remain difficult to treat. Some patients develop resistance to current therapies leading to relapse, metastases, and ultimately death.
We are proposing to use our own immune cells to treat difficult cases of breast cancer. Our approach is to modify T cells with synthetic receptors to specifically recognize and kill breast cancer cells without harming normal tissues and organs.
We are using the T cells ability to patrol our body and modifying them to recognize specific molecular signals, such as the amount of a protein (HER2) present on the surface of cancer cells, to execute potent killing responses. If successful, our approach will lay the foundation for clinical studies, potentially will have major impact on our ability to treat effectively and safely some of the most difficult forms of breast cancer and will provide new approaches to other challenging solid cancers.
Adrenocortical carcinoma is a cancer of the adrenal glands that often kills the patient. Drugs to treat this cancer have failed because current research models, which use cell lines or mice, are too different from the cancer itself. Cell lines made from the cancer only have one type of cancer cell, while the original cancer has many types of cancer cells. Mice have many types of cancer cells, but the mouse cancer is too different from the human version to be helpful. To develop new treatments for this cancer, we need to make a model that includes many types of human cancer cells.
Organoids, or “mini-organs,” are a new research model that has many cell types and can be made from human tissues. They have been used to study other cancers that were previously difficult to study. We developed adrenocortical carcinoma organoids, which grew and made hormones just like the original cancer. Here, we use these organoids to study different types of cells in the cancer to determine which cells are more likely to cause worse disease. With this information, we can target weaknesses in the most dangerous cancer cells to stop the cancer from progressing, reduce treatment-related side effects, and improve survival and quality of life for patients with this terrible cancer. We also expect that our new methods can be used by scientists studying other cancers to figure out which cells are the most dangerous, so that patients with other cancers can benefit from this research.
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