Hello! I am Michael Pezzillo, a junior at Pitt majoring in chemical engineering and pursuing minors in bioengineering and chemistry. I conduct research within the Swanson School of Engineering’s Department of Chemical Engineering under the mentorship of Dr. Steven R Little, whose lab specializes in drug delivery and immunology. My project this semester focuses on the use of agonist and antagonist drugs as a therapeutic for chronic inflammation.
For context, chronic inflammatory disorders trigger immune cells to attack the body’s healthy tissue leading to the development and propagation of disorders like arthritis, heart disease, and cancer. A driving force in inflammatory diseases is extracellular ATP (eATP), which signals through the P2X7 receptor (P2X7R). P2X7R is found in most of the body’s tissues and organs, with particularly high expression in immune cells, making it an ideal target for immunosuppressant therapies. It is known that signaling through P2X7R prompts secretion of pro-inflammatory cytokines (proteins), such as IL-1β and TNF-α. As a result, there is an aggressive cellular inflammatory response which ultimately leads to apoptosis (cell death). Other immune receptors of interest are the A2A and A3 adenosine receptors (A2AAR and A3AR, respectively). Like P2x7R, these receptors are highly prevalent on immune cells throughout the body. However, upon activation by adenosine, A2AR and A3AR signaling pathways prompt secretion of IL-10, a protein that plays a crucial role in suppressing inflammation throughout the body.
Accordingly, my research focuses on targeting P2x7R and ARs as a method of treating inflammation. My goal is to assess the effects of P2x7R antagonist and/or AR agonist drugs on inflammatory responses. Simply put, a P2x7R antagonist will inhibit receptor signaling, while an AR agonist will promote receptor signaling. Previous research has studied the effects of these drugs individually in models of inflammation, but combinations of these drugs, which could result in a synergistic effect, have not yet been explored. My goal is to examine the resulting immune cell response after being introduced to combinations of the drugs in vitro and determine their overall potential to be used as an immunosuppressant therapy.
I am honored to have been chosen as a recipient of the Chancellor’s Undergraduate Research Fellowship this semester. I hope to earn my PhD in a similar subject area, and I am confident that participating in the CURF will provide me with the skills that will make that goal attainable. I look forward to being able to further strengthen my technical research and presentation skills as a result.
Outside of the lab and classroom, you will likely find me in the audience of a Broadway show or a symphony orchestra. I have played the violin and French horn for over eleven years, so I find comfort and solace in the performing arts.