Research Summary
Focused on understanding and researching potential therapeutics for fibrosis, a group of progressive diseases that are limited to only a few current treatment options. These diseases result in organ damage that leads to recruitment and activation of immune cells and the formation of scar tissue-like fibrotic lesions that cause disruption to the local tissue structure. In many cases, this has severe effects such as organ failure and, in many cases, death. In fact, it is estimated that 30-45% of deaths each year in the United States are associated with some form of fibrosing disease. Due to the severity of fibrosis and the magnitude of which it affects many individuals, the ability to find a therapeutic to combat this would be extremely beneficial.
In the past, it has been found that fibrosis occurs through a positive feedback loop that utilizes enzymes called sialidases, also known as neuraminidases, such as NEU3. These enzymes cleave off sialic acids that are located at the ends of glycoproteins as well as latency-associated glycopeptide (LAP) that results in the release of transforming growth factor-β1 (TGF-β1). This, in turn, potentiates fibrosis. Sialidase inhibitors such as 2-acetyl-pyridine (2AP) have been shown to attenuate some forms of fibrosis such as lung fibrosis by directly inhibiting NEU3, TGF-β1 activation, and ultimately can reduce inflammation and thus fibrosis.
To better analyze how 2AP works as well as see if it is a potential therapeutic for other forms of fibrosis in various organs, immunohistochemistry and histology practices as well as methods will be utilized to provide an accurate and full image of the effect of 2AP. This includes, but is not limited to, staining with lectins and various antibodies, picrosirius red staining. Oil red O staining, immunofluorescent analysis, and more. Through these methods, I will be able to examine and later quantify specific antigens, collagen, lipids, and more to see if 2AP causes a significant reduction or increase of the tested material. By doing so, this would aid in the process of discovering the specific effects 2AP has on various organ systems as well as the possibility of it serving as a viable option and innovative treatment. Additionally, other routes of analysis and other compounds may be tested to identify other potential therapeutics as well as an in-depth look of how they play a role in combating fibrosing diseases.
Ultimately, the project is an attempt to identify possible compounds such as 2-acteyl-pyridine as a means to combat fibrosis. In turn, this can help lay the foundational work for future studies of these potential therapeutics as well as the pathways and functions they interact with that are related to fibrosis.