University of Virginia chemist Rebecca Pompano is looking for ways to turn children’s immune systems against pediatric cancers. Neuroscientist John Lukens is investigating links between gastrointestinal inflammation, dysfunctional immune responses and the development of autism.

Both have recently been named recipients of 2015 Hartwell Individual Biomedical Research Awards to benefit children of the United States. Each will receive $100,000 per year in direct research support from The Hartwell Foundation for three years.

The award is intended to inspire innovation and achievement among exceptional scientists and engineers who are pursuing cutting-edge biomedical research. In addition to the individual awards, the foundation awarded the University two Hartwell Fellowships at $50,000 per year for two years to enable specialized postdoctoral training in research areas that exemplify the foundation’s goal to improving children’s health.

“UVA is extremely pleased that two of our most innovative researchers have been selected to become Hartwell Foundation investigators this year,” said Phil Parrish, UVA’s interim vice president for research. “Their work is at the frontiers of bioscience and medicine, and holds the potential for transforming medical care for children.”

Each year, the Hartwell Foundation announces its Top 10 Centers for Biomedical Research in the United States, inviting each center to nominate individuals for a Hartwell Individual Biomedical Research Award. The foundation announced last week that, for the 10^th consecutive year, it has selected UVA as a top 10 biomedical research center, making University researchers eligible to compete for 2016 Individual Biomedical Research Awards.

The selected institutions may submit up to four nominations to compete in a process that seeks to fund early-stage, innovative and cutting-edge biomedical research that has not yet qualified for significant funding from outside sources, has the potential to benefit children, and demonstrates a clear path to clinical application.

Only investigators nominated by a participating institution selected by The Hartwell Foundation are eligible to compete for individual awards. For each funded nominee, participating institutions receive a Hartwell Fellowship to fund one postdoctoral candidate who exemplifies the values of the foundation.

With the two individual awards this year, plus the two postdoctoral fellowships, the Hartwell Foundation has honored UVA by providing $800,000 in funding. The two individual awards place UVA in the leadership position for all participating schools nationally since Hartwell began the competition in 2006. Over the course of its participation, the University has earned 12 Individual Biomedical Research Awards and 11 fellowships, for a total of $4.7 million in Hartwell funding.

Here’s a look at this year’s recipients:

• Rebecca Pompano, assistant professor of chemistry

Pediatric cancer is the second-leading cause of death for 1- to 14-year-olds. Patients suffer through aggressive therapies that severely compromise quality of life and can cause long-term damage. A potential alternative is active immunization, which uses a vaccine to recruit the child’s own immune system in fighting the tumor.

Chemist Rebecca Pompano is proposing a new way of thinking about vaccine development. (Photo by Dan Addison)

A century of experience has shown that children’s immune systems are powerfully effective at eliminating infections, once properly vaccinated. However, to eliminate cancer, a particular type of immunity called a killer T-cell response is required, and historical vaccines cannot always raise it safely. Pompano is working to identify a new generation of vaccines and immunotherapies that might sidestep serious and painful inflammatory side effects.

She is proposing a new way of thinking about vaccine development and a unique tool to predict the efficacy and safety of potential new vaccines. “Traditional approaches to vaccine design neglect the intricate organization of cells that drives immunity,” she said. “I hypothesize that the organization of cells and signals inside the lymph nodes soon after vaccination can predict the level of protection that the vaccine will provide.”

Pompano intends to build a custom “lab-on-a-chip” microfluidic platform that keeps tissue samples from the lymph node alive and stimulates them similarly to what happens in the body. By using this system, calibrated by testing it with well-characterized vaccines, Pompano will test new types of vaccines targeting neuroblastoma as a case study. This type of tumor accounts for 15 percent of all deaths from pediatric cancer.

“If successful, this project will generate a prototype therapeutic vaccine for neuroblastoma that can be moved into clinical trials with children,” Pompano said.

More broadly, she hopes to produce a testing system that can identify candidate therapeutic vaccines for many childhood cancers, including lymphoma and brain tumors.

John Lukens, assistant professor of neuroscience

Autism spectrum disorder, or ASD, has emerged as one of the most prevalent and pressing pediatric disorders in the United States. It is estimated that nearly one in every 68 American children will develop ASD, and unless preventive measures are identified, the incidence of the disorder is expected to continue increasing at unprecedented rates.

Neuroscientist John Lukens is working to develop effective treatment options that target the root causes of the majority of autism spectrum disorder cases. (Photo by Dan Addison)

Presently, treatment options that target the root causes of ASD do not exist, and currently available therapies seek only to manage the behavioral and cognitive impairments associated with ASD.

Lukens is working to develop effective treatment options that target gastrointestinal inflammation and dysfunctional immune responses, the likely root causes of the majority of ASD cases. Mounting clinical and epidemiological evidence indicate that he is on the right track; ASD is associated with dysregulated immune responses, gastrointestinal inflammation and alterations in microbiota, the varied microorganisms found in the human body.

“I propose that dysregulated immune responses are the unifying biological factor that could explain how diverse environmental factors – including maternal obesity, infection during pregnancy, population-wide changes in dietary consumption and pollutants – can all contribute to ASD,” he said.

Lukens recently discovered that inflammatory cytokines (cell secretions that affect the processes of other cells) that are generated by hyperactive immune cells can centrally contribute to the development of ASD. He also has found that aberrant regulation of the microbiota can lead to elevated systemic levels of inflammatory cytokines, thus providing a conceivable link between the microbiome and ASD. This work challenges the school of thought that ASD is only a disease of the brain.

Lukens’s work, with support from the Hartwell Foundation, has the potential to lead to fundamental changes in the understanding of the biological systems that contribute to ASD and its effects on children. His goal is to develop immune-targeted therapeutics that could offer a universal therapy or even a cure for the majority of ASD cases.