The study of inflammation, the specific activation of immune cells in response to pathogenic or toxic stimuli, is fundamentally important to understanding how the body neutralizes infections and combats chronic inflammatory stress. Research in the Amiel Laboratory focuses on studying the basic molecular mechanisms regulating cellular immune activation with the long-term goal of discovering new therapeutic approaches to manipulate immune responses to better meet the needs of immune-related clinical challenges. In the field of immunology, there is a growing appreciation of the importance of how metabolic changes in immune cells shape the types of immune responses that these cells perform. Of particular interest is the notion that manipulation of cellular metabolism can dramatically influence the type and magnitude of pathogen-specific immune responses.

The primary objective of our research proposal is to identify novel mechanisms of molecular control of cellular metabolism and to determine how these influence the activation and immune-generating potential of dendritic cells (DCs). DCs are immune cells that are important regulators of inflammation and also possess a vital function in initiating adaptive immune responses via their ability to acquire and present antigens to T lymphocytes. Prior to activation, DCs exist in a relatively quiescent metabolic state. Upon activation, DCs undergo a process of maturation that is accompanied by a profound metabolic switch in which they exhibit reduced mitochondrial function and up-regulate aerobic glycolysis. Our work focuses on elucidating some of the mechanisms responsible for inducing this metabolic switch and how these changes in DC metabolism influence the immune activation of these cells. The Amiel Laboratory uses a diverse investigative approach that includes cell biology, molecular, and biochemical approaches to investigate how metabolic signals control immune activation and function of dendritic cells.