On September 10, 2024, Keystone Symposia will host a free ePanel event featuring the recipients of the Michelson Philanthropies & Science Prize for Immunology. This international prize is a collaboration between the Michelson Medical Research Foundation and Science to support young investigators doing transformative research in human immunology, based on work done in the past three years. The winner is awarded $30,000 and the publication of his or her essay in Science.
The goal of the prize is to accelerate immunology advances with trans-disease applications towards vaccine and immunotherapy innovation. The live ePanel event will feature this year's Grand Prize winner Bingxu Liu, and Finalists Carla Nowosad and Gabriele Casirati, who represent cutting edge research across innate immune sensing and protection, adaptive memory and surveillance and targeted cancer immunotherapies. Each will present their groundbreaking work and answer live audience questions about the forefront of vaccine and immunotherapy development during the upcoming live ePanel event.
Welcome remarks will be byDr. Gary Michelson, founder and co-chair of Michelson Philanthropies and Michelson Medical Research Foundation,Bill Moran, Publisher of AAAS/Science andHolden Thorp,Editor in Chief of AAAS/Science.
Institute for Protein Design, University of Washington
Protons are the new first responders to danger: Human STING’s newfound function as a channel expands our understanding of immunity
The human immune system senses danger signals and carries out different responses. It remains a mystery how the Stimulator of Interferon Genes (STING), a critical innate immune sensor, can induce a wide range of downstream responses upon activation. Using a combination of genetic, biochemical, and structural tools, my colleagues and I discovered that human STING plays a surprising role as a proton channel. Identifying STING as the first immune-sensing channel extends our understanding of the functional diversity of immune responses. The agonist similarity and functional divergence between bacterial and human STING suggest the possibility of modularly engineering sensing and functional units of innate immune proteins for improved immunotherapies.
Bingxu Liu grew up in a village town in Henna, the central part of China. He received undergraduate degrees from Zhejiang University and a Ph.D. from Massachusetts Institute of Technology. He is currently a postdoctoral scholar at the Institute for Protein Design at the University of Washington, where he works on exploring and overcoming the limitations of natural biological systems.
Carla Nowosad – Finalist Department of Pathology, Langone Grossman School of Medicine, New York University
Who goes there? How B cells assess risk in the intestine
B cells essentially contribute to intestinal immunity through the production of large quantities of antibodies. Most intestinal antibodies are produced via germinal centers (GCs), which despite being chronically present in healthy gut-associated lymphoid tissue, were poorly understood in terms of their ontogeny and antigenic drivers. Using multicolor fate-mapping with the Confetti fluorescent allele to visualize GC clonal expansions, single-color GCs were observed in the steady-state intestine, suggesting strong antigen-driven selection events. By coupling fate-mapping, model microbiomes, and Ig sequencing, we showed that gut-GCs selected clones with increasing affinity to members of the microbiome. Mapping how antibody responses are generated in the absence of infection has major implications for understanding proper control of the microbiome, known to be an important determinant of many disease outcomes.
Carla Nowosad received undergraduate degrees from the University of Warwick and a Ph.D. from the Francis Crick Institute, National Institute for Medical Research Mill Hill. After completing her postdoctoral fellowship at Rockefeller University, she started her laboratory in the department of Pathology and the Translational Immunology Center at New York University Grossman School of Medicine in late 2021. Her research focuses on how B cells make decisions in the complex microenvironment of the intestine.
Dana-Farber Cancer Institute | Boston Children's Hospital
Stem cells in disguise: How epitope editing can empower targeted cancer immunotherapies
Adoptive immunotherapies have revolutionized the treatment of several tumors. Nonetheless, their application to acute myeloid leukemia is limited by the lack of actionable tumor-restricted antigens. Precise gene-editing of surface proteins in hematopoietic stem cells may endow them with selective resistance to chimeric antigen receptor T cells or monoclonal antibodies, thus minimizing on-target/off-tumor toxicity. We identified single amino-acid changes in the extra-cellular domain of FLT3, KIT, and CD123 that abrogate their recognition by therapeutic antibodies while preserving the proteins’ function and regulation. These mutations can be introduced, either alone or in combination, in healthy stem cells by adenine base editing and enable the selective eradication of leukemia xenografts in murine models, while sparing human hematopoiesis. Epitope editing is a new concept in cancer immunotherapy that will provide novel opportunities to target hard-to-treat hematological malignancies.
Gabriele Casirati received his MD degree from Università degli Studi di Milano and trained as a
hematologist at Università Vita-Salute San Raffaele. During 2020-2023, he worked as a research fellow at Dana Farber Cancer Institute and completed a Ph.D. in Molecular and Translational Medicine from Università Milano-Bicocca. He is currently a postdoctoral research fellow at Boston Children's Hospital. His research focuses on new gene-editing approaches to enhance targeted immunotherapies for hematological malignancies.