#TraineeTuesday: Aaron Wolfe, PhD

This #TraineeTuesday, we are introducing Aaron Wolfe, a postdoctoral associate in the Colón-Ramos Lab! Aaron recently received funding for his K99 application to the National Institute on Aging. Moreover, some of his research on the dynamics of neuronal metabolism was published in PNAS!

The manuscript marks the result of Aaron’s 2.5 years of work on how the brain supports the wide-ranging energetic demands that are required of neuron activity and firing. The brain is one of the most energetically demanding tissues, and its energy-producing metabolic pathways are all closely intertwined. Yet, it was thought that certain mechanisms of producing energy were disfavored in neurons, possibly to redirect metabolism into other protective pathways. However, it is difficult to detect and quantify these kinds of metabolic prioritizations. At the time, tools to do this real-time in living organisms were more than limited.

A collaborator of the Colón-Ramos Lab, Richard Goodman, MD, PhD from the Vollum Institute at OHSU, developed the novel sensor HYlight to investigate one such pathway of energy metabolism. Aaron took on the job of adapting this sensor for use in C. elegans, using the genetically encoded fluorescent biosensor to produce novel worm strains that encode for biosensors.

The Colón Ramos lab pursued observing whether a neuron’s dynamic localization changes were dependent on the energy state of a cell and whether such changes would have a direct effect on the metabolic changes as well. Aaron perceived that there were “fascinating,” unanswered questions about the intricate mechanisms of neuronal metabolism and that his sensor could solve this enigma.

There are two main ways that cells can produce energy in the form of ATP: mitochondria, which produce the vast bulk of cellular ATP, and the metabolic pathway of glycolysis, which breaks down glucose and subsequently produces ATP. Glycolysis was thought to be disfavored in neurons, but the HYlight sensor that Aaron developed for use in worms depicted a different story. The results displayed that different neurons were utilizing a broad spectrum of glycolytic metabolism levels, depending on their specific activity.

Based upon how different neurons favor different rates of glycolysis at their respective equilibriums, researchers believe that the function of a neuron would depend on different energetic demands and thus different metabolic profiles to support such.

Aaron creative application derives from his diverse background. Having received his BS in chemical engineering from Northeastern University, he focused on developing polymer-based synthetic vaccines at a small start-up. After, he earned his PhD from USC, continuing his application of polymer-based research by investigating the crystal structure of a human RNA editing protein.

At Yale, Aaron enjoys the “alive” environment that allows for diverse scientific conversations.

Approaching the end of his postdoc, Aaron is planning to apply for academic jobs within the next year.

In his own lab, Aaron would like to continue focusing on how different metabolic pathways interact. The current literature suggests that if few pathways branch off from a single starting point, then the starting point will be somewhat limited as cells will favor one pathway over another. Aaron thinks this “decision” can have a huge impact on cellular longevity. He suspects that this may occur over longer durations, applicable even to unexplored aging mechanisms. Therefore, he hopes to use HYlight sensor in the long-term and study how the preference for certain pathways may impact neuronal function over a lifespan using C. elegans.

Additionally, congratulations to Aaron for recently becoming a dad!