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YSM Faculty Developing “Game Changer” for Global Health

April 19, 2023
by Julie Parry

Dengue. Zika. Lyme. Yellow fever. Chikungunya virus. Malaria. These worldwide diseases, and others, are spread by the bite from an infected arthropod, a tick or mosquito. Five faculty from Yale School of Medicine (YSM) are collaborating on a project focusing on creating vaccines against infectious diseases by targeting the vector, which could be a “game changer” for global health.

The project is funded by the Howard Hughes Medical Institute (HHMI) Emerging Pathogens Initiative.

Lead investigator, Richard A. Flavell, PhD, FRS, Sterling Professor of Immunobiology, credits his colleague Erol Fikrig, MD, Waldemar Von Zedtwitz Professor of Medicine (Infectious Diseases), YSM, and Professor of Epidemiology (Microbial Diseases), Yale School of Public Health (YSPH) and of Microbial Pathogenesis, YSM; with the project concept.

The duo partnered in the 1990s to develop a vaccine against Lyme disease, so when the HHMI opportunity was announced, Flavell’s first call was to Fikrig. “When we worked on Lyme disease, we generally worked with pathogens. Erol had the idea to look at the vector. Since then, we stayed in touch and worked together on a few grants, so he was the first person I called,” said Flavell.

Fikrig’s work is concentrated on creating a vaccine to stop the vector—a tick or mosquito—from spreading a disease, rather than targeting the microbe itself, which is the premise behind this new initiative, a perfect “synergy of Flavell’s interests and mine,” Fikrig said.

If we could generate a vaccine against that agent that is transmitting all these viruses, then we could eliminate more diseases rather than targeting the microbe. It'll be a game changer if we pull this off.

Maudry Laurent-Rolle, MD/PhD

So Flavell and Fikrig set out to assemble their dream team of collaborators. At YSM, they contacted Maudry Laurent-Rolle, MD/ PhD, assistant professor of medicine (infectious diseases), for her expertise in immunology and flaviviruses, such as dengue fever; Aaron Ring, MD, PhD, associate professor of immunobiology, who developed genome screening technologies; and Heidi J. Zapata, MD, PhD, assistant professor of medicine (infectious diseases), for her background in human immunology.

They also contacted two of Fikrig’s longtime collaborators, George Dimopoulos, PhD, and Photini Sinnis, MD, at Johns Hopkins Bloomberg School of Public Health. Dimopoulos’s proficiency is in mosquitoes and CRISPR technology, while Sinnis is a world expert in malaria. They also tapped Drew Weissman, MD, PhD, from the University of Pennsylvania, for his knowledge of mRNA vaccines.

“It's really an amazing group. We are going to produce important findings, because the quality of the team and the enthusiasm of everybody. We are off to an incredible start,” said Flavell.

Besides the possible discoveries driving the excitement, both Laurent-Rolle and Zapata spoke about the mentorship opportunity this project presents.

“I am interested in human immunology, so Erol gave me this opportunity to contribute to the grant in that way. So I am going to be focusing on the host response, and it's amazing to work with Erol, Richard Flavell who is a giant in the immunology field, and Drew Weissman whose technology developed the mRNA vaccine for COVID. I'm thankful to be part of it. It's an incredible chance to work with all these amazing scientists,” said Zapata.

Laurent-Rolle spoke about the excitement in her lab to participate in this project. “I will soon have six to seven people in my lab, postdocs, a postbac, graduate students, and two people focused specifically on the HHMI project. So a really strong team of folks. I have been lucky to have these people, to get them so quickly, and to participate in this project,” she said.

HHMI committed “$100 million to support basic research targeted at preparedness for emerging pathogens that could threaten human health in the future,” they said.

“Do you remember the summer of 2019? We were all terrified about eastern equine encephalitis (EEE) virus, which is a mosquito borne disease with a 35% case fatality. This project has global impact if we are able to do this. We wouldn’t have to create a vaccine for every specific disease, if we could generate a vaccine against that agent that is transmitting all these viruses, then we could eliminate more diseases rather than targeting the microbe. It'll be a game changer if we pull this off,” said Laurent-Rolle.

Other Yale faculty participating in other projects through the HHMI Emerging Pathogens Initiative are Akiko Iwasaki, PhD, Sterling Professor of Immunobiology and Professor of Dermatology and of Molecular, Cellular, and Developmental Biology and of Epidemiology (Microbial Diseases); Anna Marie Pyle, PhD, Sterling Professor of Molecular, Cellular, and Developmental Biology and Professor of Chemistry; and Paul Turner, PhD, Rachel Carson Professor of Ecology and Evolutionary Biology. To learn more about their research, read, “Yale labs to lead new investigations into emerging pathogens.”

Submitted by Julie Parry on April 19, 2023