Paul J. Leibson, professor of immunology at Mayo Clinic in Rochester, Minnesota and a pre-eminent researcher of NK cells died of cancer on August 6, 2007.
Paul grew up in the Chicago area in a large cohesive family with strong intellectual traditions that did not confuse the importance of goodness of heart with the glamour of academic accomplishments. After graduating magna cum laude in 1974 with a BS in Honors Biology from the University of Illinois at Urbana-Champaign he earned his PhD in immunology from the University of Chicago. He received his predoctoral training in tumor immunology in the laboratory of Hans Schreiber and earned a PhD in 1979 and an MD with honors in 1981.
After a pediatric internship and residency at the University of Colorado in Denver, Paul trained for two years as a fellow in allergy-immunology with Anthony R. Hayward at the National Jewish Hospital and Research Center, where he began his work on human NK cells. He joined Mayo Clinic in 1986 for a distinguished career in immunology. During two decades at Mayo he poured himself into teaching in the classroom and laboratory, serving for five years as Dean of the Graduate School. His colleagues at Mayo recognized Paul for his service in research and teaching with the Rose M. and Morris Eisenberg Professorship and he was named Mayo Distinguished Educator for his truly premier mentoring of students, fellows, and junior faculty alike.
The name of Paul Leibson is unquestionably linked to NK cell signaling. Together with a small group of courageous scientists, he pioneered this field well before the characterization of NK cell receptors that trigger cell-mediated cytotoxicity. It was typical for the signaling section of each NK workshop to begin with a state-of-the-art presentation by Paul. For those who are not in the field of signaling, Paul’s work is essential reading. This line of research took a certain amount of faith and courage, in that the receptors that mediate one form of NK cell-mediated killing (antibody-dependent cellular cytotoxicity or ADCC) are only partially defined, while the second mechanism of target cell recognition, which leads to the ‘natural’ killing of tumor cells, has been a complete mystery. Paul left the critical work of receptor characterization to other equally skilled natural killer cell biologists, and concentrated instead on how these receptors deliver NK cell-activating signals from the plasma membrane to the cytotoxic effector machinery in NK cells.
His body of work in the 1990s spans an array of important signaling enzymes, ranging from tyrosine kinases such as Lck and Syk, to the small, Ras-related GTPases, to the lipid-metabolizing enzymes, namely the phospholipase C-gamma-1 and -2 isoforms and phosphoinositide 3-kinase. Paul’s string of publications in the 1990s offer some truly provocative insights into the inner workings of one of the more mysterious cells in the immune system. More recently, he dedicated his efforts in understanding how single NK cell receptors branch out into diverse signaling pathways rather than a single pathway. As a result, he demonstrated that NKG2D could trigger phosphoinositide release and small GTPase activation through a single non-ITAM containing adaptor, DAP10, which can recruit PI-3K and the Grb2-Vav complex. Paul's work did not always focus on positive signaling networks regulating NK cell-mediated killing. In fact, his laboratory was among the first to demonstrate that the expression of MHC molecules on target cells could inhibit cellular cytotoxicity by blocking the most proximal step in the signaling cascade, namely activation of the src kinase Lck. He subsequently went on to show, following identification of killer inhibitory receptors (KIR), that the mechanism of their inhibitory property was due to recruitment of tyrosine phosphatase Shp-1 to the KIR cytoplasmic tail.
In sharp contrast with other investigators in the field of signaling, he focused on human cells rather than mouse, reaching the same level of experimental sophistication achieved using genetically targeted mice. Indeed, his studies often preceded mouse studies and provided an accurate framework for the interpretation of the results obtained in mouse models. Paul fully recognized and acknowledged the value of studies in mice, but, perhaps due to his clinical background, remained devoted to freshly isolated human NK cell lines and cultured NK cell clones as models for the functional characterization of these fascinating cells of the immune system. His devotion to human cells came with a price. Members of the Department of Immunology were systematically tested for the quality of their NK cells and the ability of their serum to support the growth of his human NK cell clones. Those who passed either test often found themselves on the receiving end of a large needle-bearing syringe manned by the good doctor himself. However, it should be stated that Paul would not ask others to volunteer for a duty that he would not carry out himself. There is no doubt that, what we know today on NK cell signaling, is largely due to Paul Leibson's impressive work and knowledge. His work and ideas in the NK field will continue to be influential.
Paul was one of the most positive people we ever met. He showed us that every day—in fact every situation of life—is full of new and wonderful opportunities. However, he was extremely careful not to confuse optimism with reality. Instead, Paul was uncompromising in his determination to stand for truth. He loathed situations where the truth was hidden or distorted and refused to serve in situations where this guiding principle was not honored. He was truly a man of impeccable integrity. His genuine enormous curiosity in science did not impair his ability to analyze experimental results most stringently and objectively, but helped him to ask motivating questions and to propose elegant experiments in the kindest most considered way possible. Similarly, his genuine, deep, and cordial friendship extended to so many of us would never ignore a problem but focus on opportunities and solutions, often in a very humorous way. It is no wonder that the legendary camping trips he did with students, colleagues, and family were often most perfect even when it rained.
Paul enthusiastically greeted his friends. He treated each visitor that came to his office with genuine enthusiasm…making them feel at the center of his universe. Paul loved his family, his friends, and his work. Each was properly placed in his priorities with a remarkable balance. He was always happy to come to work and then to go home to his family. Thus, in addition to research and education, his passions included cooking and learning about wine, and gathering for lively discussions and story telling with family and friends. His love for nature nurtured his enthusiasm for gardening, camping, mushroom hunting, and traveling. Paul is survived by his wife Cynthia, daughter Sarah Bryan (Sean), and two brothers, David and Marc. His parents Ruth and Benton preceded him in death.
Despite losing his courageous struggle with a most aggressive, unbearable cancer that claimed his life much too early, Paul considered himself blessed, blessed by having a loving wife, daughter, brothers, and other family, friends and colleagues, and having had marvelous parents that all were so dear to his heart.
Engraved on the entrance arch of the library of Paul Leibson’s alma mater, a motto reads "Non est mortuus qui scientiam vivificavit" or "No one is dead who has given life to knowledge."