Swatting away mosquito-borne viruses

A TEAM IN I: Dr. Alan L. Rothman, pictured above, left his position at the University of Massachusetts Medical School in April to join the Institute for Immunology and Informatics, or iCubed. The post appealed to him in part because of the freedom of the work. / PBN PHOTO/BRIAN MCDONALD
A TEAM IN I: Dr. Alan L. Rothman, pictured above, left his position at the University of Massachusetts Medical School in April to join the Institute for Immunology and Informatics, or iCubed. The post appealed to him in part because of the freedom of the work. / PBN PHOTO/BRIAN MCDONALD

In April, after 24 years at the University of Massachusetts Medical School in Worcester, Mass., Dr. Alan L. Rothman left his prestigious research position to join the Institute for Immunology and Informatics, or iCubed, the research component of the University of Rhode Island’s biotechnology program, headquartered in downtown Providence.
Rothman brought with him an active, five-year, $11 million research program on dengue fever, funded by the National Institutes for Health. “My work has been in understanding what makes people sick from the dengue fever virus, characterizing the disease and how it affects, both positively and negatively, the immune system,” he said.
His new career path in Providence personifies the auspicious current reality – and the promising future – of the life sciences research sector in the Knowledge District.
Rothman said he was recruited by Dr. Anne De Groot, co-founder of the Institute, and founder and CEO of EpiVax Inc.
“After 24 years, I felt I had gone as far as I could,” Rothman said. “It was time for me to look for different challenges.” The opportunities at iCubed, he continued, are enormous. “We’re at an early stage. It’s a particularly attractive place to work. We’re doing things differently; there’s a more open approach to where this institute may go. There’s lots of building to do, and we’re not limited to where the vision could go.”
The institute, founded in 2008 by DeGroot and Denice Spero, is relatively small, with five faculty members and plans to recruit a sixth, and two technicians, according to Rothman. But it has carved out a research niche focused on newer, safer vaccines and new methods of predicting adverse responses, such as allergies. With these tools, it has the opportunity to teach the next generation of students a new way to design effective vaccines.
Much of the institute’s current work is focused on mosquito-borne tropical diseases. In addition to Rothman’s work on dengue fever, the institute is also working on design of vaccines to protect against potential bio-terror weapons employing Venezuelan, Eastern, and Western Equine Encephalitis viruses. These viruses, due to their relative ease of production, considerable stability and high aerosol infectivity, are the targets of the institute’s next-generation vaccines. Using genomes from more than 100 strains of the viruses, iCubed has sought to identify immunogenic traits shared by all three strains in order to produce a safer vaccine offering broad protection. Using the mathematical modeling process known as immunoinformatics, the institute has developed a tool kit for vaccine development. “Our first prototype vaccine for [these encephalitis viruses] looks excellent,” said DeGroot. “We’re going forward with a better design, which we will be testing this fall.”
Dengue fever is considered a neglected tropical disease, one that persists in conditions of poverty. While it is never on the list of the leading causes of death worldwide, it ends up putting lots of people in the hospital, Rothman explained, citing the recent outbreak in Brazil with more than 1 million cases of dengue. In addition, there was an outbreak of dengue fever in Key West, with the potential to spread to the rest of Florida.
While there is a low risk of catching dengue fever locally because of the kind of mosquito that transmits it, Rothman warned that people who travel in the Caribbean and South America could be at risk. “Unexpected things happen in infectious diseases,” Rothman said. “When West Nile was first introduced in the Americas, it was a new, unexpected event, which spread rapidly. Today, with all those people who are vacationing in Aruba, the Caribbean and Asia, anyone can bring dengue back to Rhode Island.”
Continuing climate change may also prove to be a factor, Rothman continued. “Each mosquito has a preferred habitat, but climate change will change habitats and ecosystems. Mosquitoes don’t care about borders; mosquitoes adapt,” he said. As far back as the 1940s, dengue fever had been the focus of research, including work by Dr. Albert B. Sabin, who developed the live oral vaccine for polio, Rothman explained. Now, some 65 years later, researchers are finally testing vaccines for use against dengue.
Rothman’s work, which is focused on “what makes people sick from dengue,” may be helpful in understanding interactions that go on the microbiologic level and uncovering the causes of how dengue virus might induce some immune responses in people to West Nile virus.
“There are not a lot of reports of people getting sick in Puerto Rico with West Nile Virus,” Rothman said, despite the fact that both illnesses are spread by mosquitoes. Currently, a vaccine for dengue fever is being tested by the Institut Pasteur in Paris. But “because dengue and West Nile are related,” Rothman said, “there is now a vaccine in development for West Nile.”
Rothman voiced his optimism for iCubed’s continued growth and its ability to serve as a catalyst to attract new researchers to Rhode Island. “We’re a small group of investigators,” he said, voicing caution about not overselling the institute. “But we hope to build great things here.”
Another important factor in the institute’s growth has been its willingness to invest in creating a hub for research for junior investigators to hone their craft.
Visiting fellows at iCubed’s Neglected Tropical Diseases Summer Work presented their work at the Second Immunoinformatics and Computational Immunology Workshop in Chicago on Aug. 1-3. They included Andres Gutierrez of the Universidad Peruana Cayetano in Peru, Robin Welsh of Smith College and Chris Eickhoff of Saint Louis University. &#8226

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