Superfund Trainee Aryatara Shakya Investigates Cellular Model for Arsenic Toxicity

March 23, 2021

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Aryatara performing lab work for her research in Dr. Donna Zhang’s lab in the College of Pharmacy, UA.

Aryatara Shakya is a second-year graduate student in the Department of Pharmacology and Toxicology under the mentorship of Dr. Donna Zhang. Dr. Zhang’s lab specializes on an antioxidant protein known as “Nrf2” which is basically a protein that regulates, or controls stress related pathways in the body. The activation or inhibition of this Nrf2 protein at the cellular level is known to lead to protection of cells against any form of damage or toxic exposure. Studies state that activation of Nrf2 can be a safe and effective strategy for chemoprevention of cancer and many other diseases.

Contaminated water, soil and air remain a major health concern and source of arsenic toxicity for both developed and developing countries. Arsenic, as an environmental toxicant is therefore a well-known public health issue that leads to several disease states such as cancer, diabetes, neurological and cardiovascular disease. However, the molecular mechanism or the molecular interactions of how this arsenic leads to these various disease states is not clearly understood. In other words, there is a gap in knowledge regarding how and what kind of malfunctions occurs within the cellular pathways regarding these processes and interactions concerning arsenic that could lead to a range of diseases in human body.

To solve any problem, the root cause must first be identified. Similarly, to be able to treat these several disease states potentially caused by arsenic toxicity, Shakya believes that we first need to understand how, what, and why Arsenic affects the human body at the cellular level. We need to dig deep down at the molecular mechanism or interactions between the therapeutic treatment and the biological target (i.e., protein, enzyme, receptor etc.) that would yield a physiological response.

Arsenic has been shown to upregulate Nrf2, the master regulator of cellular stress response. Besides “Nrf2” protein, “p97” is another protein that Shakya has incorporated into her study. P97, also known as a mighty “protein extractor” of the cell. It is a protein that maintains quality control within cells by balancing any protein related stress. Shakya is currently  focusing on studying the mechanistic link between Nrf2 and p97, and how these ultimately drive the progression of those various disease states in human body by chronic arsenic exposure. She hopes that this knowledge will eventually aid in the development of therapeutic strategies for the promotion or inhibition of oxidative and proteotoxic stress targets in the cell induced by arsenic exposure.


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