2020 SRF Summer Scholar Profile: Kaitlin Pensabene

Kaitlin Pensabene

SRF Summer Scholar, Class of 2020

Turn Biotechnologies

My name is Kaitlin Pensabene, and I am a senior at Villanova University studying biochemistry. At Villanova, I work with Dr. Aimee Eggler studying the effects of small molecule antioxidants on the Nrf2/ARE pathway. Specifically, I have been studying not only how  transcriptional but also how translational processes are attenuated by oxidative stress. In doing so, I am investigating the mechanism by which reactive oxygen species shut down global protein synthesis while selectively upregulating synthesis of cytoprotective enzymes to reverse the effects of oxidative stress in a timelier manner. While interning with Turn Biotechnologies this summer, I studied the epigenetic effects of aging on a variety of diseases. Dr. Jay Sarkar and his team at Turn Biotech are focused on creating therapeutics that reverse age-related phenotypes and their associated diseases with applications in the skin, joints, muscle, and potentially many more tissues.

The basis of Turn Biotechnologies’ Epigenetic Reprogramming of Aging (ERA) therapeutic is to turn back the clock of a cell’s epigenetic signature. Imagine a young cells epigenome as a record you just bought. When you bring it home and play it on your record player, the music sounds beautiful and the record works perfectly, not skipping a single track. The grooves in the record are each representative of a modification to the epigenetic signature, like methylation, acetylation, ubiquitination, or phosphorylation. Each individual modification alone does not give the listener a song. But, together every single one of the grooves produces a harmonious symphony of musical notes that form music, just like the sum total of all the epigenetic markings results in a perfectly functioning cell capable of responding appropriately to stimuli and carrying out complex processes necessary for life.

Now imagine you own that record for many years, playing it constantly. Eventually, the record will inevitably accumulate a few scratches, perhaps some dust and dirt, that interfere with the reading of the record on the record player. Those perfectly placed grooves no longer come together to form a beautiful song but instead end up eventually sounding uncoordinated and messy. With enough scratches and dents built up from normal wear and tear, the record will start to skip often, and the songs won’t make much sense to the listener anymore. This is analogous to the aged epigenome, which has inevitably acquired flaws as a result of normal aging processes. The resulting epigenome is not as harmonious as it once was, leading to overstimulation or suppression, inappropriate expression of certain pathways, and dysregulated cellular activities. Consequently, disease occurs along with phenotypic changes we associate with aged individuals, such as muscular decay, vision and hearing loss, cognitive decline, and metabolic dysfunction.

The inevitability of aging would lead one to conclude that such a scratched-up record was doomed to never play the same music it once did. However, if one possessed a cloth and cleaning solution that could wipe away all the dirt and imperfections on the record, it would seem that it is indeed possible to reverse these deleterious effects. ERA technology is able to do just that. By “cleaning up” the aged cell’s epigenome, ERA can restore the cell to a more youthful state capable of functioning at the same capacity it once did. The beauty of ERA technology is that there is no manipulation done on the genomic level; in other words, no permanent changes are made to the record. ERA simply allows the record to play the same music it always did, never wiping away its memory completely but instead helping it to remember how to play that music smoothly and flawlessly.

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