Fifty percent of people with Lynch Syndrome–related mutations will develop colon cancer. Over the last few years, we have started to understand that the immune system plays an important role in fighting colon cancer in Lynch Syndrome. The immune system is an army that protects us from cancer. In our project, we want to measure the strength of this immune army in patients that carry the Lynch mutation. We hope that these measurements will tell us who is at risk of developing cancer and minimizing the uncertainty of patients. Our goal is to study the immune system of patients that carry Lynch mutations in order to develop laboratory tests that one day can be used to predict which patients have a higher risk of developing colon cancer. At the same time, we hope that by studying a patients immune system we can understand the types of cells that are needed to fight cancer, and ways to develop new immune treatments to prevent cancer.
Funded in partnership with WWE in honor of Connor’s Cure
Pediatric Diffuse Midline Gliomas (DMGs) and High-grade gliomas (HGGs) are aggressive brain tumors. Unfortunately, current treatments don’t work well for these tumors. Our research shows that energy pathways play a role in making these tumors resistant to treatment. Specifically, proteins involved in energy use become more active in resistant tumors. Our recent findings suggest that disrupting these pathways could be a new way to fight these tumors.
In our upcoming study, we will test a compound that acts like glucose but interferes with energy use. We will also test other ways to target the weaknesses of these tumors. Our tests will measure protein and gene activity, energy use, and how combination treatments work.
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.
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.
Funded by the Constellation Brands Gold Network Distributors in honor of the Dick Vitale Pediatric Cancer Research Fund
Ewing sarcoma is a cancer that is most often diagnosed in teenage children and young adults. There is a need for new therapies for this disease. The goal of our work is to develop new therapies for Ewing sarcoma focused on a drug target called EWS-FLI1. Multiple studies have shown that EWS-FLI1 is a promising drug target for this disease. In a clinical trial called SARC037, we are currently testing a combination therapy that we have shown targets EWS-FLI1. The goal of the current study is to try to understand why some patients in this trial respond to the therapy and others do not. To accomplish this, we will study ways that EWS-FLI1 resists targeting. We will identify molecular differences in tissue collected from patients who had an excellent response to the therapy compared to those who did not respond. In addition, we will test these differences in the laboratory to see how they impact sensitivity to the therapy used in SARC037. The results will guide future clinical studies that seek to target EWS-FLI1. In addition, they will provide insight into how EWS-FLI1 contributes to drug resistance to more traditional chemotherapy.
Colorectal cancer (CRC) is a common and deadly cancer that often arises from abnormal pre-cancerous growth of polyps in the colon. Colonic polyps can be detected and removed during colonoscopy, therefore reducing the risk of cancer development. While most CRC cases occur randomly, about 25% of CRC cases have a familial component, including hereditary syndromes like Lynch Syndrome and Familial Adenomatous Polyposis (FAP).
Individuals with FAP have a very high susceptibility to developing CRC, requiring frequent diagnostic testing. However, for FAP patients, the number of colon polyps is often too high to be removed through colonoscopy. In these situations, patients may require surgery to remove their colon, which is costly, has risks, and changes bowel movement habits. Therefore, finding new ways to slow down the development of polyps and CRC would greatly benefit FAP patients.
Using mouse models of FAP and an intervention study in FAP patients, our study aims to develop a new approach to prevent CRC in FAP, called chemoprevention, by exploring the potential of a new substance to reduce the development and/or progression of colon adenomas. We have observed that beta-hydroxybutyrate (BHB), which is a natural substance that our bodies produce while in a starving state or when on a ketogenic diet, can slow down colon tumor growth. As there is currently no standard chemoprevention treatment for FAP, our study aims to address this critical need for effective approaches to reduce CRC risk and improve the lives of those with genetic conditions that lead to colon cancer.
Funded in partnership with WWE in honor of Connor’s Cure
Diffuse midline glioma (DMG) is a devastating and aggressive type of brain tumor that primarily affects children and young adults. Despite advancements in medical research, DMG remains a medical challenge with limited treatment options and a poor outcomes. Considering these difficulties, there is an urgent unmet need to develop new and innovative therapies for DMG. One promising avenue for discovery is the exploration of targeted agents that disrupt key signaling pathways involved in tumor progression without affecting the healthy normal cells in the brain. Our previous work has identified a potential new therapeutic target that could be leveraged in this way to specifically combat this tumor. New drugs that selectively inhibit this aberrant signaling pathway show great potential for slowing down the growth of DMG cells, thus creating a new opportunity for intervention. In these proposed studies, we will explore precisely how this intracellular signaling pathway controls cancer progression. Further, we will test in the lab whether treatment with new drugs designed to inhibit this pathway can halt DMG tumor growth. We hope that our studies inform the use of new targeted drugs to treat this devastating childhood cancer and thereby drive advancement of patient care and redefine the treatment of DMG.
Ovarian cancer (OC) is the most lethal gynecologic cancer in the US. Unfortunately, the majority suffer relapse. Patients with recurrent platinum-resistant OC respond poorly to chemotherapy.
Immunotherapy with immune checkpoint inhibition (ICI) has emerged as a promising therapy in several cancers. Unfortunately, only small fraction (10-15%) of patients with OC do benefit from immunotherapy. Therefore, effective strategies are warranted to improve the overall benefit of immunotherapy in OC. Targeting immunosuppressive factors within the tumor immune microenvironment (TME) represents an attractive approach. Our focus in this proposal is on tumor-associated macrophages in OC.
Macrophages with a specific ‘suppressor’ phenotype (M2 subtype) within TME play a significant role in promoting an immunosuppressive environment and in mediating therapy resistance. These cells are the most prominent cells in OC. However, another phonotype (M1 subtype) provides a favorable pro-inflammatory TME and enhances the immune response. Targeting macrophages and switching their phenotype from M2 to M1 is potentially promising approach that has not been investigated thoroughly before. In this study, we propose to target them with two strategies: Targeted inhibition of the transforming growth factor-beta (TGF-beta) receptor and CD47 inhibition.
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.
Lung cancer kills the most cancer patients in the world. Most of these patients are diagnosed late in their disease, and there is no cure. Having a chest CAT scan (CT scan) every year helps detect lung cancer early and reduces the chance of dying. When lung cancer is detected early, the patient has a higher chance to survive. Patients who are diagnosed with small lumps in their lungs, called lung nodules, have a higher chance of getting lung cancer. Having lung nodules can also require unnecessary, uncomfortable, and sometimes painful medical procedures that are not helpful for the patient. The purpose of our research is to help detect lung cancer earlier for patients with lung nodules, which could give them a better chance to beat cancer and survive. To do this, we propose to combine new medical test tests, from a blood draw and computer measurements from CAT scans. We will use simple blood draws to measure DNA materials in the blood that can help detect if lung cancer is present. We will also use computers to analyze hundreds of measurements from lung nodules in CAT scans that can tell us if the nodule is cancer. We will then combine the blood draw and computer measures from CAT scans using advanced math to detect lung cancer early more accurately without hurting the patient. Our goal is to improve early lung cancer detection so that it can be cured and help save patient lives.
Mailing List
