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.
Lung cancer is the deadliest cancer in the United States and lung adenocarcinoma is the most common type of lung cancer. While genetic mutations contribute to the development of cancer, cancer cells also activate gene programs over time that allow the cancer cells to become more aggressive and harder to treat. Advanced lung cancer cells evade current treatments such as chemotherapy or therapies that target the immune system. In our work, we have found that late-stage lung cancer cells expressed a unique transcription factor that activates gene programs which permit cancer cells to spread throughout the body. Of note is that these cancer cells also release molecules which we believe signal myeloid cells to enter the tumor. In doing so, the myeloid cells cause the immune system’s T-cells to be less effective and reduce how well current treatment strategies work. We seek to understand how late-stage cancer cells facilitate disease progression and how they limit response to current therapies. We have generated new mouse models which will allow us to investigate the gene programs that are active in these advanced cancer cells and to determine how these cells become resistant to therapy. Overall, our goal is to identify new options for targeting late-stage cancer cells which could be combined with, or used in place of, current treatment strategies so that we can increase how long patients with lung cancer live and improve their quality of life.
In just over the past 10 years, new drugs that improve our own immune system’s ability to clear tumor cells have become an incredibly powerful class of cancer treatments. These therapies known as immune checkpoint inhibitors or ICIs work broadly against many different tumors, providing hope for many patients to better fight off their cancer. However, each patient is unique, and ICIs can work better for some patients than others. There are many reasons for these differences, including a person’s genetics, their type of cancer, and their environment. Recently, studies including our own have shown that microbes in our bodies also affect how well ICIs stop the growth of tumors. In our lab, we aim to understand how these microbes function during cancer treatment. We focus on how microbes make molecules that stimulate our immune system, which work with ICIs to fully activate tumor-fighting cells. In our work sponsored by The V Foundation, we will find new enzymes to make these active molecules. Using these enzymes, we will build better probiotics and test whether they can help to clear ICI-resistant tumors. Together, these studies will advance our long-term goals to understand how gut microbes affect cancer treatment and to generate new bio-based therapies that improve outcomes for cancer patients.
NRAS mutations are found in about 30% of melanoma, a dangerous type of skin cancer. Although recent advancements in melanoma treatments have helped many patients, those with NRAS-mutant melanoma still face challenges. Available treatments for these patients are often not effective, and their cancer can quickly become resistant to treatment. Recently, scientists have developed new drugs called pan-RAS inhibitors that can directly target the NRAS mutations responsible for tumor growth. These drugs have the potential to greatly improve treatment for people with NRAS-mutant melanoma, but we need to learn more about potential resistance to these new drugs. This knowledge will help us develop better treatments for this type of cancer. Studying drug resistance is difficult because tumor can be very different from one another. To overcome these challenges, our study uses advanced technology to observe how individual melanoma cells grow and change. Our approach allows us to monitor the rare cells that adapt to the new pan-RAS inhibitors, helping us understand why some cells become resistant. We will also compare the genes in these adapting cells to those in cells that do not adapt to determine what makes them different. By learning how NRAS-mutant melanoma cells adapt to new treatments, we can design better therapies for patients with this type of cancer. This will help us meet the needs of people with limited treatment options and improve their chances of recovery. Our research aims to move the body of knowledge forward, positively impacting cancer patients and cancer research.
This research is focused on better understanding and improving treatments for a specific kind of blood cancer, known as B-cell acute lymphoblastic leukemia, or B-ALL. Although the treatment for childhood B-ALL has been greatly improved, long-term survival for adult patients is still under 50%. Our research showed that about 13% of adult B-ALL patients have mutations in PAX5 gene, which is critical for B-cell development. Two B-ALL subtypes are defined by PAX5 mutations: PAX5alt and PAX5 P80R. Surprisingly, survival rates vary greatly between these two subtypes (30% vs. 65%), which suggests that different genetic characteristics are involved. The goal of our research is to better understand the biological changes and genetic markers linked to B-ALL from different PAX5 mutations. Based on our preliminary study, we believe that certain PAX5 mutations block normal B-cell development, thus creating cells that are more likely to develop into leukemia. Our objectives are to 1) Explore how PAX5 mutations influence the normal DNA patterns and gene activities in B cells, and 2) Investigate how these mutations drive leukemia development step by step. We anticipate that our work will shed light on how PAX5 mutations disrupt B-cell development, thereby initiating leukemia. Our results will provide a comprehensive insight into understanding PAX5 mutations in B-ALL. This will enhance our knowledge about the role of PAX5 mutations and the mechanisms in disease initiation and clinical outcomes. Understanding these mechanisms could pave the way for more effective, targeted therapies for this high-risk leukemia subtype in adult patients.
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.
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.
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