HSRF Introduction: Gnanesh Gutta

Hi everyone! My name is Gnanesh, and I am a rising senior. I am currently majoring in Neuroscience and Sociology with a minor in Chemistry and a Conceptual Foundations of Medicine Certificate. In my free time, I play on Pitt’s Ultimate Frisbee Team, and enjoy some biking and Spikeball in the summertime.

Currently, I am working towards my professional goal of attaining my medical degree and becoming a physician. I hope to become some sort of surgeon after medical school focusing on work in surgical oncology. During my time at Pitt, I have been studying Alzheimer’s Disease due to the mystery of its underlying causes pulling me in. As my undergraduate degree is coming to an end and I look forward to my overall professional goals, I wanted to find a way to bridge my undergraduate research to research in the field of oncology as I plan to go into medical school. This is where my project for the HSRF helps me pursue those goals.

Right now, I am working under Professor Karl Herrup in the Neurobiology Department of the University of Pittsburgh School of Medicine to study the occurrence of cellular senescence in the neurons of patients with Alzheimer’s Disease through immunohistochemistry techniques. I am attempting to find correlations between DNA damage and the inductance of senescence along with a so-called “bystander effect” in the senescent neurons. Cellular senescence is a natural cell cycle arrest seen in the body’s cells as they reach their replicative limit, but it is also seen in the disease process of cancer. Senescence is also a tissue’s defense mechanism against cancers as these cells are actively prevented from cell cycle activity. The exact cause of the cell cycle arrest is unknown although it is also known to coincide with the release of pro-inflammatory factors that are together known as the Senescence-Associated Secretory Phenotype (SASP). This SASP can lead to a chronic inflammatory state in the tissue in which surrounding cells can die or develop senescent features to prevent the spread of cancer. I will correlate senescent markers with the presence or absence of DNA damage and cell death markers in both human brains and the mouse model of AD. Finally, I will use morphometry to visualize how far the dying cells are found from the senescent cells to establish how far the SASP can induce neuronal death. In the recent past, the focus in the field of AD research has shifted from the long-held hypothesis that Alzheimer’s disease is caused by amyloid plaques towards the more holistic approach of investigating the roles of natural aging processes like oxidative stress and inflammation in AD neurodegeneration. This relatively newer shift in the field, creates a lot of room for students like me to make any small contribution to explaining the largely misunderstood disease mechanism.

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