Medical school scientist named a Howard Hughes investigator

It was announced on May 9 that Akiko Iwasaki, Ph.D., professor of immunobiology and of molecular, cellular, and developmental biology, has been selected as a Howard Hughes Medical Institute (HHMI) investigator.

In addition to receiving one of the most prestigious designations in biomedical science, HHMI investigators are given the support necessary to move their research forward in creative new directions. HHMI provides each investigator with his or her full salary, benefits, and a research budget over an initial five-year appointment.

The institute also covers other expenses, including research space and the purchase of critical equipment. Investigator appointments may be renewed for additional five-year terms, each contingent on a successful scientific review.

Iwasaki is one of 27 top researchers, selected for their individual scientific excellence from a group of 1,155 applicants, to be named HHMI investigators this year.

“HHMI has a very simple mission,” said HHMI President Robert Tjian, Ph.D., when this year’s group of new investigators was announced. “We find the best original-thinking scientists and give them the resources to follow their instincts in discovering basic biological processes that may one day lead to better medical outcomes … And while we cannot predict where their research will take them, we’re eager to help them move science forward.”

Responding to the news of her new appointment, Iwasaki said, “Funding from HHMI will enable my lab to pursue questions that are risky but potentially very rewarding. We will be able to understand the types of immune responses generated by sensing different levels of danger associated with infections, and to determine how the bacteria and viruses that inhabit our body influence the immune system. Ultimately, we hope to design vaccines that effectively prevent diseases caused by viruses that enter through mucosal sites.”

Iwasaki’s body of research has addressed the mechanisms of innate recognition of viruses and the initiation of antiviral immunity.

Her lab focuses on sites where a virus encounters mucosal surfaces. Until now, most efforts to develop vaccines have focused on the immune system’s antibodies, or T cells, circulating through the body.

But efforts to harness these circulating T cells have not been effective in organs such as the vagina, intestines, lung airways, and central nervous system, which restrict the entry of these “memory” T cells.

Iwasaki’s research has thrown light on the crucial role of dendritic cells, a special class of white blood cells that form part of an early warning system against infection, in protecting the body from certain viruses.

Dendritic cells are abundant in skin and mucosal surfaces, where they act as sentinels against foreign invaders.

In a study recently published in Nature, Iwasaki’s team developed a new model for vaccination against genital herpes, a disease for which there is no effective immunization, and no cure. The researchers focused on peripheral tissue in the female genital tract, where viral exposure occurs.

Working with mice, they explored a two-part vaccine strategy they call “prime and pull”: The priming involves conventional vaccination to elicit a system-wide T cell response. The pulling involves recruitment of activated T cells directly into the vaginal tissue, via topical application of chemokines—substances that help mobilize the immune cells.

Iwasaki and colleagues found that the recruited T cells were able to establish a long-term niche and offer protective immunity against genital herpes by reducing the spread of herpes simplex virus into sensory neurons.

Other recent research by Iwasaki, published in Proceedings of the National Academy of Sciences, showed that, following influenza infection, the relationships among bacteria in the gut critically regulate the generation of the immune response’s virus-specific CD4 and CD8 T cells and antibody responses.

Her results revealed the importance of commensal (“good”) microbes in regulating immunity in the respiratory mucosa through the proper activation of multiprotein complexes known as inflammasomes.