Metabolic Regulation of Dendritic Cell Activation and Immune Function



Profile

I attended Amherst College as an undergraduate where I dual-majored in Biology and Philosophy. I received my Ph.D. in Microbiology and Immunology from the Geisel School of Medicine at Dartmouth College in the lab of Dr. Brent Berwin. I performed my postdoctoral training in the lab of Dr. Edward Pearce (currently at Washington University in St. Louis) while at the Trudeau Institute in Saranac Lake, NY. I joined the faculty of the Department of Medical Laboratory and Radiation Science at the University of Vermont as an Assistant Professor in 2013.

Research Description

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 is to identify novel mechanisms of molecular control of cellular metabolism, and 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.

Recent Publications

Everts B, Amiel E, Huang SC, Smith AM, Chang CH, Lam WY, Redmann V, Freitas TC, Blagih J, van der Windt GJ, Artyomov MN, Jones RG, Pearce EL, Pearce EJ (2014) TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKÉ› supports the anabolic demands of dendritic cell activation. Nat Immunol 15(4): 323-32.

King IL, Amiel E, Tighe M, Mohrs K, Veerapen N, Besra G, Mohrs M, Leadbetter EA (2013) The mechanism of splenic invariant NKT cell activation dictates localization in vivo. J Immunol 191(2): 572-82.

Huang SC, Freitas TC, Amiel E, Everts B, Pearce EL, Lok JB, Pearce EJ (2012) Fatty acid oxidation is essential for egg production by the parasitic flatworm Schistosoma mansoni. PLoS Pathog 8(10): e1002996.

Amiel E, Everts B, Freitas TC, King IL, Curtis JD, Pearce EL, Pearce EJ (2012) Inhibition of mechanistic target of rapamycin promotes dendritic cell activation and enhances therapeutic autologous vaccination in mice. J Immunol 189(5): 2151-8.

Everts B, Amiel E, van der Windt GJ, Freitas TC, Chott R, Yarasheski KE, Pearce EL, Pearce EJ (2012) Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood 120(7): 1422-31.

Fairfax KC, Amiel E, King IL, Freitas TC, Mohrs M, Pearce EJ (2012) IL-10R blockade during chronic schistosomiasis mansoni results in the loss of B cells from the liver and the development of severe pulmonary disease. PLoS Pathog 8(1): e1002490.

van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, Pearce EJ, Pearce EL (2012) Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36(1): 68-78.

View all Amiel publications here.


Eyal Amiel, Ph.D.

Eyal
Amiel, Ph.D.

Assistant Professor
Department of Medical Laboratory Science

 

802-656-0522
Office: 302A Rowell
Lab: 320 Rowell

Lab Homepage

Lab Members

   Phyu Thwe, CMB Student

Recent CMB Blog Posts