Thesis Defense Announcement
To: The George Mason University Community
Candidate: Douglass Dey
Program: M.S. in Biology
Date: Monday April 23, 2018
Time: 2:00 P.M.
Place: IABR, Room 1004
George Mason University
Science & Tech Campus<http://www.gmu.edu/resources/welcome/Directions-to-GMU.html>
Title: "Investigation of Small Peptide Inhibitors on PD-1 PD-L1 Protein-Protein Interactions"
Committee Chair: Dr. Alessandra Luchini
Committee Members: Dr. Lance Liotta, Dr. Claudius Mueller
This is a public defense and all are invited to attend.
Cancer is a complex disease in which abnormal cells divide uncontrollably and invade body tissues, leading to eventual organ failure and death. These abnormal cells are able to grow and spread by evading recognition and destruction by the immune system through multiple mechanisms. Utilization of immune checkpoints, which are regulators of the immune system that prevent autoimmunity, is one such mechanism exploited by cancer cells. A specific immune checkpoint pathway involves tumor cells upregulating PD-L1 or programmed death ligand 1. When bound to its receptor PD-1, or programmed death protein 1, PD-L1 prevents the anti-tumor immune response normally responsible for clearing abnormal cells throughout the body. Within the past decade, a new class of drugs called immune checkpoint inhibitors have been developed to block this interaction and unleash the patient’s immune system on their tumor cells. While these drugs have seen promising results for some patients, there are still limitations that need to be overcome. Many of the existing cancer immunotherapies are in monoclonal antibody form and have problems with specificity, tissue penetration, route of administration, and are expensive to produce. In this study we characterized and tested eight different small peptide inhibitors to the PD-1 PD-L1 pathway that were developed using protein painting, a novel technique used to identify specific hotspots within the binding interface. These small peptide inhibitors will be more specific and easier to administer than current therapies on the market.