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
Cancer immunotherapy, which uses a patient’s own immune system to fight cancer, has been very successful for some patients. But not everyone benefits. The immune system is made up of both immune cells that are both “good” and “bad” at fighting cancer. T cells are important “good” cells because they can kill cancer cells. Macrophages, however, can limit how well T cells can kill. Our lab studies how immune cells respond to cancer. In particular, we are interested in how different regions of the same tumor can have different immune cells in them. This means that some regions can have a good immune response, while at the same time, other regions have a bad response. We want to understand how the “bad” immune response regions form and how to fix them. We have identified a molecule called Cx3cl1 that some tumor cells make, which attracts “bad” macrophages. In this project, we will use a model system to study how Cx3cl1 interacts with macrophages. We will study areas of a tumor that have lots of Cx3cl1, and what happens to them when the tumor is treated with immunotherapy. We will also look at Cx3cl1, “bad” macrophages and “good” T cells in different regions of patient tumors. Our ultimate goal is to bring a “good” immune response to all regions of a tumor, so that immunotherapy will work better.
Cancer is dangerous because it grows out of control in the body. Cancer needs to consume nutrients to make the energy to grow. We discovered that colon cancer makes energy very slowly. Because of this, we want to try blocking energy production to kill the colon cancer.
We found that colon cancer has a very low level of Vitamin B1, which is required for the major energy producing pathway in colon cancer. We will test three different ways to take away Vitamin B1 to see if this could stop colon cancer. We will also try to find why colon cancer has so little Vitamin B1. In future, if our hypothesis is right, maybe colon cancer patients could eat a diet low in Vitamin B1 to strengthen the effects of anti-cancer drugs they receive.
Funded with support from Steve and Tamar Goodfellow
Colorectal cancer (CRC) is the third most common cancer worldwide and ranks as the second leading cause of cancer-related deaths. Screening plays a key role in early detection and makes CRC one of the most preventable cancers. Developing an accurate risk prediction score is crucial because it helps us identify and focus on those at high risk from a young age, enabling early screening and effective intervention. Research has shown that thousands of genetic mutations can increase the risk of developing CRC. Our goal is to convert these genetic discoveries into useful tools for clinical use. We plan to utilize advanced techniques such as CRISPR screening technology and single-cell sequencing, combined with deep learning models and statistical analysis. This approach will help us understand the whole impact of these genetic mutations better. This work aims to provide deeper insights into how these mutations contribute to the development of CRC, leading to more targeted and efficient screening strategies. Ultimately, our research is directed toward developing a sophisticated method for predicting colorectal cancer risk, focusing specifically on those who are most at risk. This could significantly change how we prevent and treat colorectal cancer.
This research aims to improve cancer treatment, specifically immunotherapy. My lab will identify factors that determine patients’ immunotherapy responses. We already know that microbes in our gut impact cancer treatment. For example, research shows that a fecal microbiota transplant can overcome immunotherapy resistance. At first, our goal was to identify which microbes impact immune responses. However, a difficulty for this research was that the regions we live in change which types of microbes are in our gut. This is a problem because it makes it hard to validate findings between regions. Our work revealed that it is not the species of microbe that impacts immunotherapy responses, as we first thought. Instead, it is the types of proteins produced by these microbes that matter. Different species of bacteria can make similar proteins, and it is these proteins that drive immune responses. We developed a new strategy to identify the proteins that bacteria are producing in the gut. Our approach reveals a relationship between proteins and treatment response. We verified this relationship in melanoma patients from different regions. For our next steps, we propose identifying non-invasive immunotherapy biomarkers. We will do this with the fecal microbiome. We expect that our research will improve clinical decisions and treatment outcomes.
Pancreatic cancer is one of the deadliest cancers because it is very difficult to treat. There are only a few treatment options available, and they do not work very well for most patients. We propose to find new therapies by studying how certain molecules, called RNA-binding proteins (RBPs), contribute to pancreatic cancer growth. RBPs are important because they control how genes are translated into proteins and ensure that the right genes are expressed at the right time and in the right amounts. When they are not working properly, RBPs can contribute to cancer development. For example, how much of an RBP is made can be affected by certain changes in the cancer cells, like how genes are turned on and off. Additionally, how an RBP works can be affected by cancer-specific modifications to its protein structure. Our research will focus on understanding what goes wrong with RBPs in cancer and how we can fix it. We will determine which RBPs and which cancer-specific modifications of RBPs are important for tumor growth and drug resistance. This will help us find answers that could lead to new therapies for pancreatic cancer patients.
Funded with support from the Michael Toshio Cure for Cancer Foundation
When a patient is diagnosed with cancer, they start treatment hoping to get rid of the unhealthy cells. But some cancers, including a common and aggressive type called squamous cell carcinoma, have an unsettling ability to resist treatment. When cancer cells escape therapy, patients may find that the tumor comes back after initially going away and that it starts to spread. Drug resistance is the main reason that cancers have been so difficult to eliminate. We know that genetic changes in healthy cells can cause cancer to form, but these don’t tell us why some cancer patients don’t respond well to treatment. My lab is developing new ways to observe how the surrounding healthy tumor environment is helping cancer cells resist therapy. We found that drug-resistant tumor cells rely on their connections with lymphatic vessels, typically considered as the waste drains of the body. Using a model of skin cancer, we are proposing a new tool to track cancer cells in their natural habitat to find how lymphatic vessels shield and protect the cancer cells. By targeting the supportive lymphatic network, we hope to prevent cancer cells from surviving therapy. We believe that our findings will lead to new ways to treat cancers and eliminating cancer relapse as a treatment fallout.
Funded by the Dick Vitale Pediatric Cancer Research Fund
We study a set of bone cancers that affect children and young adults. The treatment for these cancers has remained the same for the last 40 years – combinations of toxic medicines known as chemotherapy, followed by surgery or radiation to remove what is left of the cancer. While this strategy cures some patients, far too many children continue to die from these cancers. We believe we have found two specific weaknesses in these tumors: problems in their ability to repair damage to their DNA and a survival signal in a special pool of cancer cells known as “residual disease”. Through this research, we hope to bring new therapies to patients and cure more children with these bone tumors.
Funded by the Dick Vitale Pediatric Cancer Research Fund with support from the Scott Hamilton CARES Foundation
One major challenge in treating any type of cancer is resistance, or when a cancer stops responding to a certain type of drug or therapy. Some cancer cells may become resistant my changing the way they read and write their DNA, or the genetic blueprint in the cell nucleus. Other cells may change the way proteins are expressed on the surface, which can change their shape or ‘stickiness’ and ability to move in the body. When doctors can understand exactly how cancer cells become resistant to a certain drug, they can sometimes combine two or more drugs together to overcome this.
For some new classes of drugs, we have not even begun to explore how cancer cells might become resistant. One of these classes is nanoparticle drugs, which usually involves bringing together molecules like fats or polymers to help delivery drugs into certain cells. The goal of this research project is to identify the ways that pediatric cancer cells can become resistant to nanoparticle drugs, and find new drug combinations that are more effective and less toxic to children with cancer. Many lab-based studies of nanoparticles are performed in common cancers of adulthood such as breast cancer, and this has led to new treatments in the clinic, but there have been very few studies of nanoparticle drugs in childhood cancer. Currently, there is only one nanoparticle drug approved for use in children. By studying resistance to nanoparticle drugs in a deadly childhood brain tumor, we can take the first step towards a new clinical treatment for these children.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Neuroblastoma is a childhood cancer that develops from nerves outside of the brain. Half of these cancers spread and cause high rates of death despite treatment. Many researchers study how proteins impact cancer growth and spread. Proteins work differently when sugars are attached to them. Sugars are added to proteins through a process called glycosylation, and the way that sugars are added is different in adult cancers. Few people have studied how glycosylation changes the behavior of childhood cancers. We have applied new technology to studying neuroblastomas and found that a certain sugar, fucose, is decreased in advanced tumors. We will extend our work and look at how sugars change when cancer cells are treated with chemotherapy. We found that decreased levels of fucose increases the ability of certain immune cells to find neuroblastoma cells. We have proposed studies to determine how proteins joined to fucose change how neuroblastomas are recognized by white blood cells. The proposed work will be the first use of this technology to define how cancers cells change their sugar patterns to avoid death when treated with chemotherapy.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Neuroblastoma (NB) is a type of childhood cancer that is difficult to treat after it has spread throughout the body. Using animals that develop aggressive NB, we found different types of tumor cells that may lead to cancer spread. We are proposing to look very closely at these different tumor cells and determine how they may lead to NB spread and drug resistance in patients. We will also test new targeted drugs for their effects on NB spread and through our studies, new ways to treat aggressive childhood cancer may be found.
