TCRF
Funded Research

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).

Breast cancer is the second leading cause of cancer-related death in women. Immunotherapies harness the body’s immune system to fight cancer, holding great promise to prevent recurrence and prolong survival. Immunotherapies have been less effective in patient’s with breast cancer in part, due to the recruitment of suppressive cells that prevent an anti-tumor effect. We will investigate strategies to decrease suppressive signals within the tumor, allowing anti-tumor signals to successfully eliminate tumor growth. We will also determine differences in suppressive signals between early versus metastatic breast cancers to improve response to immunotherapy for patients with all stages of disease.

Cisplatin-based chemotherapy has been widely used for treating a variety of solid tumors including breast, lung and ovarian cancers. Although initial therapeutic success is achieved, a number of tumors are found to be intrinsically resistant or gradually develop resistance to cisplatin treatment, which greatly limits its therapeutic potential. Notably, cisplatin belongs to the platinum compound family, which are known as the only heavy metal containing drugs used for chemotherapy. Our proposed research will focus on a growth-related signaling pathway, named the Hippo pathway in regulating heavy metal-induced stress response, which results in a unique mechanism accounting for the cisplatin-based chemo-resistance.

To identify circular RNAs abundantly expressed in Undifferentianted Pleiomorphic Sarcoma and illuminate how circRNAs catalyze cancer-promoting and drug-resisting conditions in the microenvironment surrounding tumor cells. In particular, we will study how circRNAs merge with RNAbinding proteins to powerfully modulate tumor cell secretions, which in turn forge a tumor-protective niche that renders many existing therapies ineffective against UPS. Finally, we will use newly developed molecular techniques to manipulate circRNAs in tumor cells, paving the way to design transcriptional therapies against UPS, and to use circRNAs to refashion the tumor microenvironment, rendering this intractable disease newly vulnerable to previously failed therapies.

Cellular immunotherapies, in which a patient’s immune system is genetically engineered to target cancer cells, are revolutionizing cancer treatment. However, these engineered cells do not always persist long-term in patients, which can lead to disease relapse. I propose that the DNA structure of these engineered immune cells changes over time, ultimately impairing the expression of receptors which target the cancer cells, and that these changes can lead to treatment failure. I will examine genetically engineered immune cells from patients receiving them for cancer treatment for this phenomenon, and correlate the DNA structural changes with engineered receptor expression and therapeutic response.