My name is Rohan Desai, and I am a third-year undergraduate student currently working in the lab Maj-Linda Selenica, PhD, to study the effects of TDP-43 proteinopathy in the multi-etiology of the Alzheimer’s Disease (AD), LATE, and FTD spectrum. Having dedicated nearly two years to the Selenica Lab, I can definitively say that nothing feels as rewarding as discovering something previously unknown to the field. Moreover, Dr. Selenica’s unwavering commitment to pushing the boundaries of my knowledge each and every day has been a great source of inspiration. Unfortunately, the rise of AD prevalence nationwide further emphasizes the need for advances in this field.

I have received several recognitions pertaining to my work in the lab. I received first place in the 48th Annual Naff Symposium Poster Competition, third place in the 2023 Department of Chemistry Undergraduate Poster Competition, and was designated Outstanding Poster Award winner during the 2022 Markesbery Symposium on Aging  and Dementia.

My current project focuses on the effects of hypusinated eIF5A on TAR DNA-binding protein 43 (TDP-43) pathology as well as neurodegeneration, neuroinflammation, and brain metabolism. Among eukaryotic proteins, eukaryotic translation initiation factor 5A (eIF5A) stands alone as the only known protein that undergoes hypusination, a unique post-translational modification. This intriguing modification involves the conversion of lysine (K) to hypusine (hypk50) through the 2-step enzymatic activity of deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). Our laboratory has previously shown that it plays a major role in TDP-43 phosphorylation and aggregation. By inducing this modification through viral injection in a TDP-43 transgenic mouse model, we were able to further investigate this pathway.

Our findings have yielded valuable insights into the impact of hypusinated eIF5A on the brain. Most importantly, we were able to show that inducing hypusination led to an increase in TDP-43 aggregation, neuroinflammation, and neurodegeneration. Our data also showed that this modification has a substantial impact on brain metabolism. However, there is still much to unravel regarding the underlying mechanisms that drive these effects. Thus, some of our future projects hope to take a deeper look at the two key enzymes, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH), that push this process forward.

To date, I have had the privilege to present this data at several conferences, including but not limited to: AAIC 2022, the 2022 Markesbury Community Symposium, the 48th Annual Naff Symposium, and the Department of Chemistry Regional Undergraduate Poster Competition. However, numerous questions remain about hypusination and its intricate relationship with TDP-43 and neurodegenerative diseases. Thus, I am excited to continue this research and explore more of the unknown with Dr. Selenica here at the Sanders-Brown Center on Aging.