University of Vermont

Research at The University of Vermont

Working to Fine-Tune the Immune System

EYAL AMIEL, PH.D., ASSISTANT PROFESSOR OF MEDICAL LABORATORY AND RADIATION SCIENCES

Microbiologist Eyal Amiel, Ph.D., didn't think he wanted to study immunology, let alone make a career of it. But as co-author of a paper recently published in the journal Nature Immunology, Amiel is at the forefront of research that could eventually lead to changes in vaccine design, along with new approaches to treating immune-related diseases.

Amiel's research focuses on dendritic cells, which are critical to the immune system; their function is to process antibody-generating materials, or antigens, and present them to T cells, which then shape the immune response. His study considers the cellular upregulation of glucose, which maintains a cell's energy but also creates fatty acids that are secreted by the cell as part of its immune activity. Together with his colleagues, Amiel determined that the early consumption of glucose is vital to the activation of cells, in terms of the production and secretion of proteins that are essential to the cells' immune function. Amiel is already bringing these findings from mouse to human, having spearheaded a memorandum of understanding with the Champlain Valley Physicians' Hospital in Plattsburgh, N.Y., which will provide his lab with human blood cell filters, a waste product. The lab will reverse flush the white blood cells out and fill them with cultures, allowing them to make new observations about the innate

"The immune system is constantly riding that fine line between how much protection we can have without too much collateral damage ... It's really that fine line that makes immunology so interesting."

— Eyal Amiel, Ph.D.

Amiel's graduate work at Dartmouth, where he earned a doctorate in microbiology and immunology, focused on the two categories of receptors and the relationship between them — signaling cells, essentially the "on" switch to the cell's immune protection program, and recognition molecules that facilitate the engulfment of bacteria — and how they cooperate to bring bacteria to the surface. He found that if you take away some of the interactions between the two, you can push that fine balance of the immune system into problem areas like sepsis.

At New York's Saranac Lake-based Trudeau Institute, Amiel undertook a postdoctoral project, in which he studied the metabolic regulation of dendritic cell activity. When dendritic cells are activated, they undergo fundamental changes in their use of nutrients, increasing dependence on sugar consumption. Specifically, he wanted to gain an understanding of why cells change their metabolism when they're activated, whether that is necessary for their activation and what happens if it is modulated. By understanding the metabolic switch in both directions, Amiel hypothesizes we could increase immune activity where we might want to — in vaccines, for instance — or we could dampen it where that would be advantageous, as in autoimmune disease or hyper-inflammatory conditions.

In February 2014, Amiel received a patent for a method of producing activated antigen presenting cells and potential methods of using them in anti-cancer vaccines. He's looked at the application of dendritic cells on a melanoma model in mice, and his lab is beginning research into glutamine, which shares many properties with glucose, but may be more important in governing what cells do. One finding Amiel's lab has made is that the activation of dendritic cells means a shortening of their lifespan, which they've determined is metabolically linked. By manipulating key metabolic pathways, Amiel says, they can toy with their activation and cell survival, something that could result in dendritic cells that have both longer lives and bigger immune responses than their normal counterparts, and would therefore be beneficial in mounting an immune response to a tumor.

"The immune system is constantly riding that fine line between how much protection we can have without too much collateral damage," Amiel says, noting that the system is based on being toxic to the non-self. "It's really that fine line that makes immunology so interesting."

Last modified May 19 2014 03:58 PM