Three students in the Whiddon College of Medicine’s Basic Medical Sciences Graduate Program were awarded this year’s Dean’s Predoctoral Fellowships. The one-year fellowship program offers up to three $30,000 awards annually to Ph.D. students with Whiddon College of Medicine faculty as primary mentors.
Faculty sponsor: Wito Richter, Ph.D., associate professor of biochemistry and molecular biology
Project description: “Obesity continues its pandemic spread and has become a main driver of poor population health. Chronic, systemic inflammation is characteristic of pathologic obesity and is thought to perpetuate the disease and promote associated metabolic abnormalities such as diabetes or atherosclerosis.
“Our lab has observed that the expression and activity of Type 4 cAMP-phosphodiesterases (PDE4s), a group of enzymes that inactivate the second messenger cAMP, are upregulated in models of obesity and overconsumption, and that genetic or pharmacologic inactivation of these enzymes in cell and animal models of obesity reduce inflammation, fat accumulation, and metabolic abnormalities.
“With this Dean’s Fellowship, I will test the overall idea that PDE4 inactivation can break the vicious cycle between overconsumption and inflammation and identify specific PDE4 enzymes as novel therapeutic targets in obesity and metabolic disorders.”
Faculty sponsor: Robert Barrington, Ph.D., professor of microbiology and immunology
Project description: “Herpes stromal keratitis (HSK), caused by herpes simplex virus 1 (HSV-1) infecting the cornea, is the leading cause of infectious blindness in developed countries. Treatment for this disease is challenging due to antiviral resistance, necessitating novel therapeutics to treat HSK. Our goal is to uncover novel therapeutic targets to treat HSK by investigating how immune cells provide protection in the HSV-1 infected cornea.
“This award allows me to continue this exciting research. I am currently preparing my first manuscript, and with this support I'll also be attending a national conference to present our work. Lastly, receiving this competitive intramural award will make me more competitive for postdoctoral positions for the next stage in my career.”
Faculty sponsor: Jon Audia, Ph.D., professor of microbiology and immunology
Project description: “Amyloid-β (Aβ), a key hallmark of Alzheimer's disease pathophysiology, has recently emerged as an antimicrobial peptide and a key component of the innate immune response. To gain further insight into the role of Aβ in innate immune responses, we infected wild-type and App knockout (KO) mice with P. aeruginosa. In addition to increased mortality, our infection model showed that App KO mice had fewer neutrophils in the lung at 48 hours post-infection compared to wild-type mice. Neutrophils are a type of white blood cell that is an important part of the immune system and helps the body fight infection. Strikingly, even with reduced neutrophil infiltration, a greater percentage of the neutrophils were immature in the App KO mice. Based on this, we reasoned that Aβ might signal to help recruit neutrophils into the lung.
“To test this, we treated human lung endothelial cells with Aβ and showed an increase in surface expression of ICAM-1, which plays a critical role in neutrophil extravasation into tissues. Therefore, we hypothesize that Aβ is required to sustain neutrophil infiltration to limit lung injury during P. aeruginosa-induced sepsis.
“I am very thankful for this award so I can continue developing this project and highlight a new Aβ signaling role.”
