Congratulations to James W. Ibinson, MD, PhD, A. Murat Kaynar, MD, MPH, and Marsha Ritter Jones, MD, PhD, who were all recently awarded UPP Foundation Grants to conduct the following research projects:
James W. Ibinson, MD, PhD: “Investigating the Link between Pre-clinical Alzheimer’s Disease and Postoperative Cognitive Dysfunction Using Functional Neuroimaging”
Postoperative Cognitive Dysfunction (POCD) is a poorly understood complication of surgery and/or anesthesia that results in significant morbidity, especially in the elderly. Current evidence suggests that the rate of POCD one week post-surgery, regardless of procedure, in patients over the age of 65 ranges from 30-40%. Neither the mechanism nor the key cerebral substrates of POCD have been convincingly determined in humans. This lack of understanding hampers our ability to measure POCD’s effect on cognitive function, monitor its natural time course, and precisely quantify the effects of potential treatments. Interestingly, new research has exposed a potential link between POCD and pre-clinical underlying Alzheimer’s disease (AD). The objective of Dr. Ibinson’s proposal is to generate pilot data examining the hypothesis that elderly individuals who experience POCD after surgery also possess the altered functional connectivity neuroimaging pattern characteristic of pre-clinical AD and that these connectivity alterations will strengthen after surgery.
A. Murat Kaynar, MD, MPH: “Aerobic Glycolysis and Long-Term Outcomes from Sepsis”
Dr. Kaynar and his research group developed a model of surviving sepsis in the fruit fly, Drosophila melanogaster. The fly has the inherent advantages of providing an understanding of some sepsis pathologies due to its short lifespan, conserved pathogen recognition pathways, and presence of only the innate immune system. The Kaynar research team used the model to replicate human sepsis conditions, in which survivors have a shortened life expectancy. The flies surviving sepsis had altered glycolytic activities, closely mimicking the aerobic glycolysis (“Warburg effect”) seen in malignant cells. Once the research team modified the metabolic balance from aerobic glycolysis back to oxidative phosphorylation, the flies lived significantly longer. The UPP grant will help to identify the molecular mechanisms behind this observation and open a path to new clinical trials.
Marsha Ritter Jones, MD, PhD: “Neurturin as a Modulator of Neural-immune Communication”
The major objective of this project is to understand the role of neurturin, a neurotrophic factor, in regulating the profile of immune cell populations in both the skin and dorsal root ganglia (DRG) and hence, in modulating the response to inflammatory challenge. C. albicans will be used to infect the skin of mice that overexpress neurturin and the time course of this infection (as compared to infected wild type mice) will be evaluated. In addition, the types of immune cell populations that infiltrate the skin and DRG in response to neurturin overexpression in uninfected and C. albicans infected skin will be determined. Finally, neurturin will be injected intradermally into the skin of wild type mice and the infiltration of immune cells will be evaluated.