By Christina Cook

Almost a million Americans fall ill with pneumonia each year. Nearly half of these cases require hospitalization, and 5-7 percent are fatal. Current vaccines provide protection against some strains of the disease, but, according to University of Pennsylvania sophomore Ivan Ye, the severity of the problem speaks to “an increasing need for a universal vaccine.” 

The University Scholar from Iowa City, Iowa, has been conducting research this summer to develop just such a vaccine under the guidance of Hao Shen, associate professor of microbiology at Penn’s Perelman School of Medicine. Ye says the opportunity to contribute to such important research as an undergraduate “was a major factor in deciding to matriculate at Penn.”

The University Scholars Program at the Center for Undergraduate Research and Fellowships connected him to a research mentor, Brian Keith, adjunct professor of cancer biology in the School of Medicine. Ye credits Keith with helping him find research opportunities that would match his interests.

Ye had been involved in biomedical research throughout high school, and, while he was still interested in biomedical engineering, he wanted to use the opportunity to try something new.

“I recalled reading about interesting research at the Perelman School of Medicine on T-cell therapy and how it was being used to treat various diseases,” he says. “With the help of Professor Keith, I searched online for labs that focused on immunology and T-cells research.”

This search led him to apply for a summer position in Shen’s laboratory and to submit a research proposal detailing the work to the University Scholars Program. Once Ye’s proposal was approved, he wasted no time in preparing for the project.

“I was so honored that Professor Shen not only accepted me and allowed me to learn and work in his laboratory, but he also assigned me a project and asked one of his postdoctoral fellows to train me eight to 10 hours per week.”

Ye says that starting last November postdoctoral fellow Yan Wang showed him how to run the necessary experiments step by step and taught him the basic lab techniques and methods he would need for his summer research position. Ye also spent much of the year reading articles that Shen and Wang suggested, and he attended their weekly lab meetings. 

By the time June arrived, Ye was fully prepared to take on his role as an active member of Shen’s research team.

“My research project builds off the current projects in Dr. Shen’s lab by examining human clinical isolates to supplement the strains used in the lab.”

Ye’s work this summer involves isolating and growing bacteria obtained from pneumonia patients, then testing the resulting strains of pneumonia to see if they are infectious. If they are, he then determines if they can provide immunological protection against different strains and from there analyzes the immune response to see if it is caused by antibodies or T-cells.

He says that, “currently, vaccines can only provide protection against a set of Sp [pneumonia] strains. However, if the type of T-cells responsible for providing immunity independent of serotype can be pinpointed, a vaccine can be developed to promote the T-cell response, providing immunity against all strains of Sp.”

Ye notes that Shen’s lab was the first to discover the ability of certain pneumonia strains “to provide protection against invasive challenge from other serotypes of Sp infection,” adding, “although other labs discovered similar results with other strains, they only focused on the colonization of bacteria. Dr. Shen’s Lab focuses on the pneumonia aspect, which is why I would say Penn is a major contributor in this field of research.”

The strides that Shen and his team are making toward a universal pneumonia vaccine “would be incredibly useful for people who are especially vulnerable to Sp infection,” Ye says. 

This especially vulnerable population includes older adults, young children and immunocompromised individuals, for whom pneumonia is particularly dangerous.

“In fact,” he says, “pneumonia is primarily caused by the bacterium Streptococcus pneumonia, which is currently the leading cause of invasive bacterial disease in children and the elderly.”

Such an extent of pneumonia-related complications and fatalities, says Ye, makes developing a universal vaccine against pneumonia critically important. And, beyond even that, he says the research also has the potential to “provide a framework for conducting research on other bacteria —  important applications for the field of immunology.” 

The extensive research experience Ye had in high school set the stage for his work at Penn.

He says that “the three-year biomedical research project at Virginia Tech really piqued my interest in conducting medical research and provided me with first-hand experience in the scientific research process.” 

His research project involved “medical imaging for cone-beam CT scanning, with the goal of developing more efficient CT techniques. Working with a faculty member three years later,” he says, “I designed a new scanning scheme that employed multiple X-ray sources to improve data acquisition speed and quality.” 

After the design was finished, Ye proposed ways to “actually build such a system,” adding, “a mechanical implementation of the scanning design in this project could be used in biomedical and industrial settings, such as cardiac imaging of small animals.” 

Ye later published his research in the Journal of Optical Engineering and was invited to present it at an international SPIE Optics + Photonics conference in 2012. As extensive as his research experience was at this point, he knew he still had a lot more to learn and knew that Penn was the ideal place learn it. 

Here, he faced new challenges both in and outside the lab. 

In terms of lab work, he says “the biggest challenge so far has been growing the clinical isolates in vitro and in adult mice. Unlike other Sp strains, the clinical isolates need a lot of nutrients and grow much slower. In addition, not all of the clinical isolates are virulent in mice.” 

Outside the lab, his biggest challenge has been learning to balance the demands of his research with his classes and other activities. 

“Lab experiments can vary in length,” he says, “because it is difficult to anticipate if the bacteria will grow well or not. If bacteria grow slowly, it means I must stay at the lab until I obtain the results for a particular experiment. When school starts again, I’ll have to plan each experiment carefully to make sure there won’t be any time conflicts between academics and research.”

Ye’s long-term goals are to earn an M.D. and a Ph.D. In time, he hopes to become a “physician-scientist in the medical field and make inspiring discoveries that will improve human health.” 

His fascination with “asking questions and finding answers” is what fuels his work towards these goals. “And,” he says, “there are still many questions that need to be answered.”