TCRF
Funded Research

Glioblastoma is the most common form of brain cancer. Despite treatment, most patients do not live beyond 2 years from diagnosis. The standard way to surgically remove this tumor is to use guidance from magnetic resonance imaging or MRI. However, there is evidence that what MRI shows as tumor edge is not the true tumor margin. I have utilized a new type of MRI that identifies the pH (the acidity of a substance) to visualize these previously invisible cells. In addition, I have identified a specific receptor on the surface of these acidic cells called SLC4A4 involved in regulating the acidity of cells. I will investigate how removing these acidic cells at the margin of the tumor effects patients and if targeting this receptor can treat tumor cells by changing the tumor acidity. For the first time, we are researching the use of pH to target glioblastoma cells in hopes to improve treatment for this deadly disease.

All forms of cancer begin with genetic alterations in otherwise healthy stem cells. Yet, these alone are insufficient to predict when a person might develop the disease or how severe it might be. This raises the possibility that nongenetic events within the tumor ecosystem play a role in unleashing tumorigenesis. The goal of this proposal is to determine how the lymphatic system shapes the stem cell oncogenic landscape throughout cancer initiation and progression. We found that tumor-initiating stem 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 cancer cells and aid their spread to other parts of the body. A successful outcome of our studies holds promise for the development of therapeutics that block early cancer progression and pave the way to combat advanced metastatic disease.

Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2030. More than half of cases are only discovered once the disease has already spread into other organs, with the liver being the most common site of metastasis. Despite this, most preclinical work studying pancreatic cancer has been done in models of cancer localized to the pancreas. Using metastasis models, my laboratory has found different programs are driving how cells communicate with each other in pancreas and liver tumors. We expect these will lead to weaknesses that can be exploited to slow the growth of tumors in the liver or possibly prevent the establishment of metastasis from happening. Our focus on this aspect of the disease has a significantly higher probability of identifying successful approaches that will transform clinical care.

Cancer is a leading cause of death. A cancer treatment called TIL therapy can cure patients, even when other treatments have failed. TIL therapy consists of surgically removing a tumor, isolating immune cells from inside the tumor, and then injecting the immune cells back into the blood of the person from whom the tumor was removed. The immune cells can naturally move around the body and kill cancer cells, but one of the main problems with TIL therapy is that the immune cells do not live long enough to completely kill all sites of disease. Here we propose to strengthen the immune cells so that they can live long enough to kill all cancer cells in the body. Our approach involves turning the immune cells into stem cells that have the capacity to make copies of themselves and live a long time. This would provide a big advance in the field so that more people suffering from cancer can be cured with TIL therapy.

This research’s focus is on how to increase the durability of cancer treatment responses and prevent the emergence of drug resistance; specifically identifying new therapeutic targets and approaches which eradicate minimal residual disease that persists in patients after initial treatment responses. This work has the potential to reveal new therapies which will transform transient responses into cures for patients.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas for which the only effective therapy is surgery and NF1 patients have a greater risk of developing these tumors from plexiform neurofibromas. These tumors are collectively known as Peripheral Nerve Sheath Tumors (PNSTs). One area of active research in plasma medicine is the use of cold atmospheric plasma (CAP) in treating tumors. In this proposal, we want to investigate the role of CAP in treating NF1-related PNSTs.

Colorectal cancer (CRC) is the second-most lethal cancer in the United States causing 50,000 deaths annually. Cancer is caused by alterations in genetic material called mutations, however correcting such changes remains unfeasible. Additionally, non-genetic structural and chemical changes are essential for cancer to gain aggressive growth potential and evading therapy. Although such non-genetic changes are essentially reversible using therapeutic drugs, details of how and when they occur during CRC progression remains unknown. Using cutting-edge human CRC and mouse model systems, we will characterize the non-genetic changes during CRC growth and identify novel factors that can be targeted for innovative therapies.

Recently we have discovered ways to reinvigorate the immune system to fight cancer. However, in immune cancers such as lymphoma, the line between cancer and the immune system is blurred. This presents an opportunity to learn how immune cells attack cancer under complex conditions, which is called the tumor microenvironment. I propose to use a spatial protein analysis technology to identify clues, not just in cancer cells but also in the embedded immune cells, that predict cancer outcomes. Further, I will study how genetically engineered anti-tumor immune cells operate in the tumor microenvironment to improve their efficacy.

Measuring DNA produced by colorectal cancer (CRC) in blood (ctDNA) is a new method to detect return (recurrence) of CRC. We developed an in-house, blood-based ctDNA test that is less costly and easier to apply in practice. We will compare our ctDNA test’s performance to a commercial ctDNA test for detecting recurrence in patients who no longer have CRC and tumor growth or spread in patients with existing CRC. We will also analyze our test’s potential to predict recurrence in localized rectal cancer, which can be helpful to identify candidates who can be spared from unnecessary surgery (ostomy bags).