Marion Pepper, PhD, Associate Professor. Department of Immunology, University of Washington, Seattle, USA
The 2021 ICIS-Luminex John R. Kettman Award for Excellence in Interferon & Cytokine Research Mid-career recognizes Marion Pepper, PhD as being in the very top tier of the current wave of mid-career immunologists who continue to make cytokine research exciting.
While a graduate student at the University of Pennsylvania, Marion pioneered the use of transgenic parasites that expressed model antigens in a series of studies to understand the events that lead to T cell production of IFN-gamma required for resistance to this pathogen. This was followed by studies that were the first to show that plasmacytoid DC (pDC) were activated during non-viral infections and acted as a source of early IL-12 required for resistance to this infection. At the time the predominant dogma was that pDC did not present antigen and her studies, were perhaps one of the first showing that pDC from sites of inflammation could present antigen. It was during this time that she developed an interest in the ability to manipulate pathogens but also to identify the relevant antigenic peptides recognized by T and B cells that mediate long-term adaptive resistance to infection, which remain the core principles of her scientific career.
As a postdoc in Marc Jenkins’ laboratory in the Center for Immunology at the University of Minnesota, Dr. Pepper focused on how CD4+ effector populations translate into memory cells. To determine if paradigms about T cell memory largely described for CD8+ T cells, applied to CD4+ T cells she generated reagents and techniques to investigate the longevity of antigen-specific CD4+ T cells initially in response to infection. Using MHC Class II tetramers to track bacterial-specific CD4+ T cells, she demonstrated that unlike CD8+ T cell memory, CD4+ memory slowly waned over time. Dr. Pepper’s finding that CD4+ memory T cells can decline because they compete poorly for IL-15 is one of the few insights in the field as to how vaccine immunity could fade over time. These studies also showed that the route of bacterial infection directs the acquisition of specific effector functions (Th1 and Th17 cells) and memory potential within a given epitope-specific population. These were the first studies of an endogenous antigen-specific CD4+ T cell response from the pre-immune repertoire through the memory phase and provided insights into the cytokine pathways critical for these events. This work was followed by studies that focused on elucidating the signals provided by IL-2 that drive the differentiation of two well-defined subsets of CD4+ memory cells, lymph-node homing central memory cells (Tcm) and tissue homing effector memory cells (Tem). Importantly, these studies also defined some of the early differentiaiton cues for Th1 effector and B cell helping T follicular helper (Tfh) cells that leads to the formation of Tem and Tcm, respectively.
Since establishing her own laboratory in the Department of Immunology at the University of Washington, Dr Pepper continued to address how early cytokine production influenced CD4+ T cell memory formation and showed that IL-2 signaling is required for both Th1 and Th2 tissue resident memory (Trm) formation in the lung.
Her lab has also focused on determining how malaria-associated inflammation influences CD4+ T cell and B cell memory formation and has developed novel tetramers to study human and mouse cells to the same malaria antigen. Understanding key interactions between B and CD4+ T cells, and how this influences the generation of both memory populations is an ongoing focus of her lab. Most recently, she defined the role of B cell priming in the generation of Th1 Tfh/Tcm responses during malaria. Her work on both T and B cell responses provided an important foundation that allowed her to pivot to study the development of long-lasting, functional antigen-specific T and B cell responses to SARS-CoV-2 in patients with mild infections. This independent body of work illustrates Dr. Pepper’s capacity to initiate meaningful projects and integrate newer technologies to perform impactful studies to understand how cytokines impact on the generation and maintenance of T (and B) cell responses in diverse biological settings.
Dr. Pepper will give a talk at Cytokines 2021 Hybrid Meeting in the opening session on “It’s all about the cytokines”, Sunday, October 17, 2021 in Cardiff and on the virtual meeting platform.
This award generously supported by Luminex Corporation recognizes a mid-career investigator who has made outstanding contributions to the field of interferon or cytokine biology. The awardee will receive a $5,000 cash prize that covers meeting registration, and where applicable travel support to the ICIS annual meeting for presentation of his or her research in an award lecture. The award is named after Dr. John R (Jack) Kettman, an immunologist who was instrumental in the development of Luminex’s technologies and the Luminex Corporation.
A nominee must be an ICIS member in good standing* who is within 15 years from their terminal degree (Ph.D., M.D., or equivalent). A nominee must be an independent research scientist (PI); postdoctoral fellows are not eligible. Eligibility of the nominee will be checked at time of nomination and before presentation of award.
*This award is intended for a mid-career researcher with a maximum of 15 years post-degree. It is, however, recognized that there may have been family-related, personal, or other circumstances resulting in extended time out of the laboratory. Exceptions to the 15-year limit will be considered based on a description of any special circumstances.
Dr. Kettman received his undergraduate degree in biochemistry at the University of California, Berkeley, and completed his Ph. D. at Oregon State University under the advisory of TE King. He completed his postdoctoral work in immunochemistry with E. Benjamini and immunobiology with RW Dutton. He was a member of the Basel Institute for Immunology 1972-1973 and spent twenty eight years as on the faculty of the Microbiology Department at University of Texas Southwestern Medical School in Dallas, Texas. He currently serves as a Professor Emeritus in the Department of Immunology, at the University of Texas Southwestern Medical School at Dallas. Jack was a co-founder of Luminex Corporation and former member of Board of Directors (1995) and a partner and member of board of Directors, Radix BioSolutions, Georgetown TX. He is author or co-author of over one hundred publications in reviewed scientific Journals.