Faculty awarded intramural grants to further research

The USA College of Medicine recently announced the recipients of the 2022 Faculty Intramural Grants Program Research Awards, which provide funds for basic science or translational research through an annual competitive program.

Jonathon Audia, Ph.D., with Amanda Tuckey

The awards allow faculty to develop new research ideas through seed funding, develop new critical preliminary data for revised extramural proposal submissions, or enable sustained research progress between extramural grant funding periods, also known as bridge funding.

This year’s recipients are Jonathon Audia, Ph.D., professor of microbiology and immunology; Natalie Bauer, Ph.D., associate professor of pharmacology; Jin Hyun Kim, D.V.M., Ph.D., assistant professor of microbiology and immunology; Wito Richter, Ph.D., associate professor of biochemistry and molecular biology; and Victor Solodushko, Ph.D., associate professor of pharmacology.

Audia received $25,000 for an additional year of bridge funding. The long-term goal of the project is to develop new therapeutic and diagnostic targets to improve the outcomes of critically ill patients with pneumonia, acute respiratory distress syndrome (ARDS) and sepsis.

Natalie Bauer, Ph.D.

Bauer’s lab is studying pulmonary arterial hypertension (PAH), a disease in which the blood vessels of the lung are damaged. She received $25,000 in funding to explore extracellular vesicle signaling in the pulmonary circulation. Extracellular vesicles are nanosized particles released from cells that are in circulation all the time and help keep blood vessels healthy.

“Our work focuses on using healthy extracellular vesicles to deliver the second messenger cAMP to the pulmonary circulation to help repair this injury and possibly improve heart function in the disease,” she said. “We are currently focused on animal models of PAH but plan to expand to patient samples in the future.” 

The goal, Bauer said, is either to reverse or prevent further damage to the pulmonary circulation during PAH.

Richter received a $50,000 grant toward developing novel therapeutics that target obesity and associated metabolic syndromes. Obesity and its comorbidities – including insulin resistance, high cholesterol, hypertension and chronic inflammation – have become major drivers of poor population health and increasing healthcare burdens.

Wito Richter, Ph.D., right, with Edward Fiedler

Type 4 cAMP phosphodiesterases (PDE4s) are a group of enzymes that help to regulate inflammation in the body. Non-selective PDE4 inhibitors have established therapeutic benefits, weight-reducing and anti-inflammatory effects. However, adverse effects, including nausea, vomiting and diarrhea, have long limited the clinical utility of these drugs, Richter said. 

“We will identify the specific PDE4 isoforms that represent the most promising therapeutic targets in metabolic syndromes, paving the way for development of subtype-selective PDE4 inhibitors as novel therapeutics targeting obesity and associated metabolic syndromes,” he said. 

Richter said this pilot study serves to generate critical preliminary data in support of subsequent extramural grant applications.

Solodushko received $50,000 in support to test the efficacy of a novel, easily modifiable influenza A vaccine. The influenza virus is constantly mutating, which requires frequent updates of vaccine antigens to ensure that the vaccine-induced immune response defends against relevant viral strains that are circulating in the community.

Victor Solodushko, Ph.D.

Solodushko’s lab has developed a technology to produce a replication-restricted virus, which is a virus that can infect normal human cells but cannot replicate once inside. This generates an immune response without causing disease. This technology will allow investigators to rapidly modify any influenza virus circulating in the community (the parent virus) for use as a vaccine. 

“The next step is to test these modified viral vaccines in mice to see if they protect against influenza infection,” he said. “If the vaccines generated using this method can protect animals against a lethal infection with influenza, it may provide a way for vaccine companies to rapidly respond to new, potentially pandemic, influenza strains.”

While a flu vaccine is the primary method of preventing influenza infection, remedies known as antivirals can help patients – particularly the immunocompromised, young and old – recover from infection. 

Kim, who received $50,000 in funding, said, “There is an unmet need to develop antivirals that are less likely to give rise to a resistant virus. In my lab, we are developing a novel approach by targeting how the influenza virus reproduces.” 

Jin Hyun Kim, D.V.M., Ph.D.

The flu virus can easily mutate its genetic material, allowing it to “run away” from the antivirals, Kim said. The genetic material of influenza viruses is fragmented into eight different pieces. When flu viruses are produced in infected cells, they follow an assembly process to put these pieces together to create new progeny viruses. 

“Though we do not fully understand how this assembly process happens, it is evident that viruses carry specific mechanisms called packaging signals that describe how to create this eight-piece in order,” Kim said. With the help of intramural funding, his team is seeking a way to block the virus assembly process and disrupt this order. 

“We believe our antiviral approach is less likely to make antiviral-resistant viruses, unlike current antiviral drugs,” he said.