Mahoney Research

The goal of our research is to understand how the molecular and cellular signaling that underlies tissue homeostasis is co-opted during disease progression. Our work has shown that intercellular communication through cell-cell adhesion, as well as the release of cytokines, chemokines, growth factors, and extracellular vesicles is well-coordinated and plays a key role in tissue morphogenesis, wound healing, and cancer development. Our current work focuses on the role of miRNAs and lncRNAs in regulating the transition between inflammation and proliferation during wound repair and how perturbations of these RNA moieties promote tumor development. Our deep appreciation of the tightly regulated wound healing network gives us a unique, precision medicine-based perspective when we apply this to biomarker research in our lab. To this end, we investigate the state of these molecular players in plasma-derived extracellular vesicles from head and neck cancer patients to see which pathways are being harnessed to promote disease progression. Ultimately, we aim to identify markers of response to immune checkpoint inhibitor therapy while illuminating the molecular framework that constitutes these distinct patient subsets.

1. Exploring the molecular framework that defines the Dsg2 Regulatory Loop in wound healing
2. Molecular profiling (mRNA, miRNA, and proteins) of HNSCC patient plasma-derived small extracellular vesicles
3. Engineering targeted small extracellular vesicles loaded with specific miRNAs

We study how the cadherin, desmoglein 2 (Dsg2), when not in the desmosomal junctions, localizes to membrane lipid rafts and caveolae and can 1) activate signal transduction through EGFR and c-SRC; 2) promote the release of cytokines, chemokines, and growth factors; and 3) modulate the endosomal pathway leading to the release of small extracellular vesicles or exosomes.

Wound healing is a highly complex response to injury with four distinct, yet overlapping phases, hemostasis, inflammation, proliferation/migration, and remodeling. In order for wound healing to progress properly, initiation and resolution of the inflammatory response is required. Specifically, we study the crosstalk between miRNAs and lncRNAs that regulate the inflammatory/proliferative transition in wound repair

We perform molecular profiling (mRNA, miRNA, and proteins) of HNSCC patient plasma-derived extracellular vesicles to identify markers that indicate responsiveness to immune checkpoint inhibitor therapy.