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.
Prostate cancer is a type of cancer that affects men, and it’s one of the most common types of cancer in the United States. Castration-resistant prostate cancer is a more advanced stage of the disease, which is harder to treat and can be life-threatening. Our research focuses on a protein called TRIM28, which is found at high levels in castration-resistant prostate cancer. We’ve discovered that TRIM28 promotes the growth of cancer cells by activating a specific oncogene. We believe that blocking TRIM28 could be a new way to treat castration-resistant prostate cancer, especially in patients who have lost an important tumor suppressor gene called RB1. Our goal is to develop new drugs that can block the activity of TRIM28, which could help to stop the growth of cancer cells and overcome cancer drug resistance. By better understanding the role of TRIM28 in castration-resistant prostate cancer, we hope to find new ways to treat this disease and improve the lives of patients.
Volunteer Grant funded by the V Foundation Wine Celebration in honor of Paul Dugoni and in memory of Lynn Dugoni
Cancer immune therapies that trigger the body’s own immune system to fight tumors have greatly improved cancer treatment over the last 10 years. Still, most patients do not benefit from this approach for reasons that remain unclear. The goal of our work is to determine what prevents the immune system from fighting cancer in order to design better immune therapies that can help more patients. Our studies focus on T cells, the immune cell type that plays the biggest role in killing tumor cells. T cells can kill cancer cells because cancer cells have mutations that T cells see as dangerous to the body. In theory, T cells that see different mutations should be able to work together to control tumors. However, our research has shown that T cells compete with each other to fight tumors and this greatly reduces the effectiveness of the T cell response. T cell competition may explain why some patients do not respond well to immune therapies. Our work is aimed at understanding why T cell competition occurs so that we can design immune therapies that promote T cooperation to better fight tumors. Our research will explore cancer vaccines as one potential treatment approach. We focus our studies on lung cancer, which causes the most cancer deaths each year, though we expect our results will be relevant to many cancer types. Findings from our work will allow development of more effective immune therapies for cancer patients that will decrease suffering from this terrible disease.
Funded with support from The Orr Family Foundation
Lung cancer is the most common source of cancer-related death in the U.S. and worldwide. Lung cancer is a heterogeneous disease, with multiple subtypes characterized by different genetic and molecular profiles, and different response to treatment. One subset of lung cancer is caused by the loss of a gene called LKB1, and approximately 50,000 people are diagnosed with this type of lung cancer in the U.S. each year. Currently, no available therapies elicit sustained clinical benefit for patients with LKB1-mutant lung cancer, and the current overall survival time for such patients from the time of diagnosis is less than one year. Thus, there is great unmet need to rapidly discover and translate clinical options to help these patients. Our recent work has discovered a mechanism of therapeutic resistance (an explanation why tumors do not respond to therapy) that is specific to LKB1-mutant lung tumors. We discovered that two available, clinically-tolerated drugs together can overcome this mechanism, and we are working toward clinical translation of this finding. However, we predict that this finding is only the tip of the iceberg, and that we are poised to discover additional promising therapy approaches as well. Therefore, it is now imperative to fully characterize the mechanisms of therapeutic resistance in this tumor type, as we will do in this project, to expand our understanding of how to treat patients with this disease. The hope is that this study will pave the way toward improved therapeutic options for patients with lung cancer.
Sarcoma tumors is a rare cancer that starts in our body’s connective tissues. These cancers spread quickly and less than 40% of people survive more than a year after it spreads. We need better treatments. One big issue is tumor hypoxia, or a lack of oxygen in the tumor. When tumors grow fast, they cannot get enough oxygen, which makes it hard for our bodies and treatments to fight off the cancer.
We have come up with a new method to get oxygen directly to the tumor using special materials called gas-entrapping materials (GeMs). These GeMs are made in a way similar to making whipped cream in a coffee shop. We plan to use GeMs to deliver oxygen to the tumor, which we believe could make treatments like immunotherapy work better and more safely.
Our research goal is to use a new series of GeMs to release oxygen into the tumor to help fight tumor hypoxia. Making GeMs is simple, cost-effective, and uses components considered safe. We think that using GeMs to increase oxygen could make immunotherapy more effective for spread-out sarcoma tumors.
We hope our research will show that these materials can be safely used with immunotherapy to help the body’s immune response fight the disease. This could mean a new way to get oxygen to tumors and could change how we treat sarcoma and other cancers that have spread to other parts of the body.
Cervical cancer can be prevented with regular exams that detect precancerous lesions. However, these lesions are common and their progression to cancer is uncertain, resulting in unnecessary invasive procedures such as biopsies and their associated consequences of pain, bleeding, and scarring. Black women are disproportionately affected by these lesions and respective consequences. Black women also have different vaginal microbiomes (VMB) than their white counterparts. The VMB, comprising microorganisms in the vagina, has been linked to these lesions and could be a target for improved screening.
Our preliminary data suggests that the VMB’s protective effect may be influenced by race. To understand whether racially distinct pathways contribute to precancerous lesions and what factors influence them, we will recruit 90 Black and 90 white women with abnormal cervical cancer screenings. We will analyze VMB profiles, HPV viral load, and stress levels at two timepoints. Our goals are to determine if racial differences exist in HPV and VMB dynamics and assess the role of stress in disparities of lesion regression. We will also explore how HPV and VMB changes mediate the stress-regression relationship differently based on race.
This research will improve our understanding of the impact of VMB, HPV, and stress on lesion regression and racial disparities. By uncovering these factors, we can develop targeted interventions to improve the health outcomes of all women.
Cancer arises from alterations, termed mutations, of a cell’s genetic material (DNA). Understanding how different types of mutations promote cancer cell growth requires precise modeling of these mutations in tumor cells in order to discern how they specifically impact cell function. We propose to do this for two proteins that are frequently mutated in ovarian cancer. These proteins, CTCF and BORIS, bind to the DNA and can change the DNA’s structure to turn genes on or off. However, how their mutations affect the DNA binding for these two proteins and impact ovarian cancer cells is unclear. We propose to generate cellular models of BORIS and CTCF mutations and measure their impact on DNA structure and gene expression. From these data, we will discern the molecular alterations and functional consequences of their mutation. The goal is to define the mechanism by which these frequent mutations impact ovarian cancer cells, with the ultimate hope that such mechanistic insights can lead to novel therapeutic approaches to ovarian cancer.
Myeloid neoplasms (MN), including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), are fatal diseases because they are highly resistant to therapy. Ultimately, efforts at preventing MN might be the most successful way to eradicate this disease. Clonal hematopoiesis (CH) is thought to be the origin of MN. CH is a process whereby a hematopoietic stem or progenitor cell (HSPC) acquires a mutation (alteration in the nucleic acid sequence) that leads to a growth advantage compared to normal HSPCs. CH can be detected many years prior to a person developing MN but as of yet, there are no established therapies to prevent progression of CH to MN. We hypothesize that CDK4/6 inhibition might be a potential treatment to prevent MN through halting the progression of CH. Here we seek to: 1) further characterize the potential of CDK4/6 inhibitors to prevent CH expansion through analysis of pre-existing clinical trial data; and 2) using mouse modeling evaluate the potential of CDK4/6 inhibitors to inhibit CH independent of chemotherapy. If successful, this work will justify the development of clinical trials using CDK4/6 inhibitors to prevent CH from progressing to MN in high-risk populations. In the long term, we hope to use targeted approaches to eradicate high risk CH mutations to prevent the development of MN.
Acute myeloid leukemia (AML) is one of the most common and aggressive types of blood cancers. Even though we have made exciting progress and have stronger treatments available, around 30% of AML patients who receive treatment will experience a relapse and have a very low chance of survival. Therefore, we need to figure out how these diseases develop and become resistant to treatment. It has been proposed in AML, there are certain cells that have stem cell-like qualities, which allow them to evade therapy and cause the cancer to come back even after treatment. In this project, we will use advanced techniques to investigate how these cells acquire such characteristics by having specific chemical changes on messenger RNAs. Our ultimate goal is to develop new treatments that can improve the lives of people suffering from these deadly diseases.
Pancreatic cancer kills just about every patient that has it. Patients are first seen with advanced disease and rarely respond to current treatments. More advanced therapies are needed to save lives. Recent studies suggest that pancreatic cancer cells are especially reliant on cellular recycling processes for growth. Mouse models of pancreatic cancer show that blocking these recycling processes can decrease the growth of tumors. These results have led to the launch of several clinical trials. However, initial results from these clinical trials show that pancreatic cancer cells stop responding. The tumors become resistant to blocking recycling pathways. We have made pancreatic cancer cells resistant to these therapies in the lab. We will use these cells to uncover better therapies to prevent resistance and increase patient survival.
Previously, research showed that these recycling processes promote tumor growth. But, in some contexts these same recycling processes can block pancreatic tumor growth. Researchers still don’t know how or when this switch happens. This dual role could contribute to the therapeutic resistance seen in patients. To study this phenomenon, I will use mini-pancreatic organs, called organoids, that can be grown in the lab. For the first time, we will be able to study the mechanisms that regulate the dual roles of cellular recycling in pancreatic cancer. Together these studies will allow us to target the tumor promoting functions of the recycling pathways while preserving the tumor blocking functions. This will prevent resistance and increase patient survival.
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.
