Pediatrics and Molecular Microbiology and Immunology
Children's Hospital Los Angeles
non-coding RNAs and cancer, tumor microenvironment, exosomes, drug resistance, cancer and inflammation, cancer epigenetics
My research focuses on the role of microRNAs and other non-coding RNAs (ncRNAs) in human carcinogenesis and drug resistance development. Specifically, my research is interested in investigating the role of non-coding RNAs in the cell-cell communication within the tumor microenvironment and better understanding how this non-coding RNA mediated cross-talk affects cancer growth, dissemination and response to treatment. I have previously shown that cancer cells secrete microRNAs within microvesicles called exosomes. In particular, two microRNAs (namely miR-21 and miR-29a) released by cancer cells can be uptaken by macrophages in the tumor microenvironment. Cancer-secreted miR-21 and miR-29a are then able to reach and bind to Toll like receptor 8 (TLR8) in the surrounding immune cells and trigger TLR8, leading to activation of the NF-B pathway and to an increased secretion of cytokines (such as IL-6 and TNF-) which in turn promote cancer growth and metastatic potential (see Figure 1). I am particularly interested in identifying new ways to impair this aberrant cross-talk between cancer cells and immune cells within the tumor microenvironment. This goal can be achieved through different mechanisms (see Figure 2) such as: 1. Inhibiting the ability of cancer cells to secrete ncRNA-containing exosomes; 2. By targeting tumor associated antigens present in the surface of cancer cell released exosomes; 3. By interfering with the ability of immune cells to uptake cancer-released exosomes; 4. By interfering with the ability of the microRNAs to bind to TLR8. In addition to these goals my research is currently investigating new possible mechanisms of action of microRNAs and other ncRNAs which might lead to a better comprehension of their role in gene expression regulation and more generally in cancer cell biology.