Dr. Andrew Leidal

• Extracellular vesicle secretion in cellular quality control and intercellular communication
• Extracellular vesicles for diagnostics and therapy

My laboratory focuses on understanding how extracellular vesicle secretion affects cell survival and behavior in diseases including cancer. Although extracellular vesicles play important roles cellular quality control and cell-cell communication, the mechanisms that contribute to their biogenesis and the repertoire of signaling molecules they encapsulate remains poorly understood. Importantly, we recently discovered that a cellular recycling pathway termed autophagy, can repurpose intracellular molecules for secretion in extracellular vesicles. This newly discovered secretion pathway operates in diverse cell types and is exploited by cancer cells to mitigate intrinsic stresses as well as reprogram the tumor microenvironment and distant tissues during cancer progression. Furthermore, we recently revealed that autophagy inhibitors including hydroxychloroquine and its derivatives, which are in clinical trials as combination therapy for pancreatic and lung cancers, strongly potentiate autophagy-dependent secretion of extracellular vesicles. Together, these observations suggest that autophagy-dependent extracellular vesicles and their cargo may have utility for the detection of cancer and monitoring therapeutic efficacy. Research in my lab centers around two broad goals: 1) to delineate the molecular mechanisms and (patho)physiological impact of autophagy-dependent extracellular vesicle secretion; and 2) leverage this understanding to for the diagnosis and treatment of cancer and other common age-related diseases.