Those of us who become a part of the UAB family quickly realize that we are a part of a diverse and special community. The research that takes place on our campus is world renowned as being on the cutting edge. Our graduate students are quite fortunate to be able to contribute to this research. Paul Mangan is no exception.
Paul received his Ph.D. in microbiology from UAB this August. Before Paul came to study here, he graduated with a degree in biochemistry from the University of Notre Dame. After working as a pre-doctoral researcher at the National Institutes of Health (NIH), he decided to pursue a Ph.D. After receiving encouragement from two UAB dental students he met at the NIH, Paul decided to look into the biomedical research programs at UAB and discovered that they were among the best in the country. “After visiting UAB for the CMB recruiting weekend I was tremendously impressed by the warm sense of community and collaboration among the students and faculty, which is what ultimately motivated me to choose UAB”, Paul commented. “I am still grateful to those two UAB dental students, because if it were not for their recommendation, I never would have considered this excellent University, which has made all the difference in my scientific training.”
Paul worked with his mentor, Dr. Casey Weaver, on his research project which concerns the processes whereby a class of immune cells, called helper T cells (Th), is localized to different tissues throughout the body in response to infection or injury. He elaborates, “I was interested in understanding the trafficking properties of two major classes of helper T cells, T helper 1 (Th1) and T helper 2 (Th2) cells. Th1 cells mediate defenses against intracellular bacteria and viruses, whereas Th2 cells defend against infection by extracellular worms called helminthes. Overactive, Th1 responses have been implicated in diseases such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and transplant rejection. Aberrant, Th2 responses are associated with allergy and asthma. The initial molecular interactions that lead to the recruitment of Th1 cells to inflammatory sites were relatively well established; however the mechanisms whereby Th2 cells were recruited were poorly understood. Therefore, I sought to research the processes that enable Th2 cells to localize to inflamed tissues.”
The research in Paul’s lab led to the discovery of a third subtype of blood cell. Paul explains, “A little over a year ago, it became apparent that Th1 and Th2 cells might not be the only two helper T cell subtypes. Our lab published that a third lineage of helper T cells existed that was distinct from Th1 and Th2 cells. These cells were characterized by their production of a proinflammatory chemical mediator, or cytokine, called interleukin (IL)-17. Thus, these cells were named “Th17”. In previous reports, these Th17 cells were shown to be strongly associated with a growing list of autoimmune diseases that were once thought to be mediated exclusively by Th1 cells, including experimental autoimmune encephalomyelitis (EAE) and type-II collagen-induced arthritis (CIA), which are mouse models of multiple sclerosis and rheumatoid arthritis, respectively. Although we established that Th17 was a distinct lineage of helper T cells, it was unclear what was responsible for the development of these cells. With a view toward ultimately defining the trafficking properties of this new lineage, I became very interested in the developmental requirements for Th17 cells. I discovered that a cytokine called transforming growth factor-beta (TGF-â) was critical to the differentiation of Th17 cells. The finding that TGF-â was important to the development of a proinflammatory type of helper T cell was unexpected given that TGF-â was typically associated with the suppression of immune responses. Nevertheless, at least two other reports, one from the United Kingdom and the other from Harvard University corroborated this discovery. This finding is a breakthrough in our understanding of the biology of Th17 cells that could ultimately aid in the development of therapies for a number of autoimmune diseases associated with Th17 responses. With regard to my own research, this discovery enabled me to differentiate a robust population of relatively homogeneous Th17 cells to perform what we believe is the first characterization of the trafficking properties of these cells.”
Paul has obviously had some positive experiences during his academic career here at UAB. When asked about these experiences, he listed the following:
- Working with my outstanding mentor, Casey Weaver has been an enormously rewarding experience. Not only has he been tremendously helpful for advancing my scientific training, but also he has been an invaluable asset to me in guiding me to the next stages of my career.
- I had the opportunity to collaborate with a number of different investigators at UAB and at other institutions both in the U.S. and abroad.
- The students in my program have become some of my closest friends and an important support structure for helping me to succeed in graduate school.
- Participating in Graduate Student Research Days in 2005 and winning third place.
- My marriage to my wife, Kristin who is also a graduate of UAB, earning a Master’s Degree in Special Education in 2005.
- The birth of my son, Connor in May 2006.
Paul will continue his research as a postdoctoral fellow at the University of Pennsylvania in Dr. Gary Koretzky’s lab. We wish Paul the best in all his endeavors.