TCRF
Funded Research

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.

Clonal hematopoiesis describes a common pre-cancerous condition where blood stem cells gain mutations in cancer-associated genes that allow them to grow and expand abnormally. This condition occurs more frequently with increasing age and after chemotherapy for solid tumors where it is a strong risk factor for developing secondary blood cancers. Inflammation after chemotherapy exposure is known to favor proliferation of mutant blood stem cells. We are investigating the anti-inflammatory effects of metformin on mutant blood stem cell behavior and how the presence of clonal hematopoiesis impacts clinical outcomes in women who received curative-intent chemotherapy after surgery for advanced breast cancer.