HOPE - Human Organs, Physiology, and Engineering

Influenza vaccines range from 10-60% efficacy per season, but what if we could predict who will respond best—and why? #HOPE Performer Lisa Wagar and team used human #ImmuneOrganoids and systems biology to build a predictive model that distinguishes responders from non-responders across 100 donors and 7 influenza antigens (AUROC=0.96 for inactivated flu vaccine!) Results reveal significant immune cell variability and response dynamics that can't be fully explained by demographic factors alone, and importantly, identify novel predictors and correlates of immune protection. This approach is scalable, easily adoptable, and can be inclusive of diverse population subsets—the very populations we aim to protect. By combining computational modeling with in vitro validation, the model offers a data-driven path toward more effective and personalized vaccines, moving beyond trial-and-error approaches to rational vaccine design. Find the full study here: https://lnkd.in/eV5hZWDP and the publicly available predictive model code at: https://lnkd.in/eNj4V3kw HOPErs: Zachary Wagoner, Suhas Sureshchandra, PhD, Erika Joloya, Jenna Kastenschmidt, PhD, D. Huw Davies #Bioengineering #PredictiveModeling #Vaccines #HOPEProgram #WellcomeLeap

A major challenge in #immunology is the lack of robust human lymphoid tissue models—a critical gap that limits our ability to study immune responses, develop #vaccines, and refine #immunotherapies. A recent Nature Materials opinion piece highlights the urgency of this issue and showcases exciting progress from the #HOPE Program. Ankur Singh and team have developed synthetic #organoids that better replicate human immune environments, advancing #scalable, #functional models that bridge the gap between in vitro and in vivo #human immune responses. Check out the News & Views here: https://lnkd.in/eFj4YhJM #Bioengineering #ImmuneOrganoids #Bcells #HOPEProgram #WellcomeLeap

What happens when you bring #immunologists and #engineers together to tackle a real-world problem? A breakthrough solution to better predict #human immune responses to #vaccines and #immunotherapy. In an exciting collaboration, #HOPE Performers Peter Loskill and Lisa Wagar combined #OrganOnChip technology with an advanced #tonsil #organoid model to create a human #lymphoid-tissue-on-chip that more than doubles the longevity of state-of-the-art lymphoid tissue cultures and enables longitudinal observation of functional vaccine response. Led by Claudia Teufel, the team demonstrated the production of flu-specific antibodies and assessed how different antigen delivery modes impact the strength and quality of human immune responses. Read the full study, out as a pre-print here: https://lnkd.in/eJukntBi #HOPE authors: Anna-Sophie Schlemmer, Zachary Wagoner, Lena Christ, Eduardo Brás, Julia Marzi #Bioengineering #ImmuneOrganoids #HOPEProgram #WellcomeLeap

#Immunocompetent #OrganOnChip platforms are transforming the way we predict human responses to #vaccines and #immunotherapies. And the field is finally acknowledging and rewarding the utility of these advanced in vitro models. Congratulations to #HOPE Performers Peter Loskill, Julia Marzi and team at the University of Tuebingen and NMI Natural and Medical Sciences Institute for receiving a €6M breakthrough award from Carl-Zeiss-Stiftung! This follow-on support will advance the #TumorOnChip and integrated technologies established during the Program to develop novel and personalized #cancer #immunotherapies. Kudos to HOPE trainees Ibra Maulana, Claudia Teufel, Hannah Graf, Lena Christ, and Julia Alber for your hard work and well-deserved recognition. #Bioengineering #HOPEProgram #HOPETransition #WellcomeLeap

A paradigm shift towards the adoption of in vitro, tissue-based preclinical models starts with efforts to demonstrate their predictive capabilities.?#HOPE Performers Ankur Singh, Andres Garcia, Ahmet F Coskun, Jeremy Boss, Krishnendu Roy and team have done just that, showcasing the feasibility of using engineered cell-matrix and cell-cell interactions to mimic the human lymphoid tissue microenvironment, thereby enabling the prediction of immune responses in both healthy and diseased B cell models. In a recent study led by Monica Zhe Zhong, the team developed human immune organoids that replicate germinal centre structures, sustain long-term immune reactions, and rapidly produce antibodies. The model was further proven effective in uncovering new mechanisms of human immune cell dysfunction when organoids were formed using B cells derived from patients with lymphoma. Biophysical properties of the engineered matrix improve culture longevity and allow for creating immune organoids from peripheral blood—an easily accessible tissue with the added advantage of longitudinal sampling, ideal for immune disease monitoring. ? Explore the full study here: https://lnkd.in/dw224r7A ? HOPE authors: Manuel J Quinones Perez, Zhonghao Dai, Valeria Juarez, Eshant Bhatia, Christopher Carlson, Zhou Fang, Thomas Hu, Mayar Allam, Adriana Mulero-Russe, PhD, Ana Mora Boza, PhD ? #Bioengineering #ImmuneOrganoids #Bcells #HOPEProgram #WellcomeLeap

Exciting new research from #HOPE Performers Peter Zandstra, Megan Levings and Fabio Rossi at the School of Biomedical Engineering at UBC uses #spatialomics to reveal key sex differences in early postnatal T cell development in the #thymus. Led by Laura Stankiewicz, this valuable study not only deepens our understanding of how the immune system develops differently in males and females, but also provides a framework to develop more targeted therapies for each. Check out the full paper here: https://lnkd.in/eS4kWFsA HOPE authors: Kevin Salim, John Edgar, Ross Jones #Tcells #multiomics #Immunology #HOPEProgram #WellcomeLeap

Lab-grown organs are becoming more than science fiction as advancements in #stemcell engineering and #bioprinting push organ manufacturing closer to reality. But even engineered tissues face the challenge of immune rejection. In a new study, #HOPE Performers Jennifer Lewis and Leonardo Riella MD PhD present a translational workflow to evaluate immune responses to engineered tissues, bringing us one step closer to overcoming this hurdle. Read more in their latest publication: https://lnkd.in/eNZNcV37 HOPE authors: Thiago J. Borges, Yoshikazu Ganchiku, Jeffrey Aceves, Ronald van Gaal, Sébastien Uzel, Jonathan Rubins, Ryuji Morizane #OrganTransplant #Kidney #Immunology #HOPEProgram #WellcomeLeap

Advances in #scSeq have opened up new ways to investigate the diversity of our immune system. Do blood measurements truly represent tissue immune responses? Enter the largest and most diverse #TCR study to date. #HOPE Performer Lisa Wagar and team at UC Irvine took a deep dive into the T cell landscape, profiling millions of cells from 10 donors – 20x more cells per donor at 100x greater sampling depth than in typical studies. The results? A TCR repertoire that is fundamentally different than what was previously known from blood alone, with minimal overlap between clones found in blood versus tonsils. These findings challenge our previous understanding of immune cell diversity and could transform the way we build preclinical models to test vaccines and immunotherapies. Read the full study, out as pre-print here: https://lnkd.in/eJUp4tcE Suhas Sureshchandra, PhD, Jenna Kastenschmidt, PhD Annie Moisan, Andreas Mayer, Naresha Saligrama #Tcells #scRNA #TCRseq #HOPEProgram #LifeSciences #WellcomeLeap

The Human Organs, Physiology, and Engineering (HOPE) program (2021 – 2024) was a $50M initiative bringing together experts in life sciences and engineering to advance human tissues, organoids, and scalable organ platforms. The HOPE program built a community of researchers focused on replicating complex human organs and immune system interactions with enormous implications for advancing cancer, autoimmune, and infectious disease interventions and, eventually, to bioengineered, scalably-produced, immune-tolerant organs for transplantation. This is where those researchers continue to interact about their work. Follow this page to see their progress, publications, event announcements, and transitions. Learn more about how HOPE could transform healthcare by reducing drug development costs and addressing the organ transplant waitlist crisis. https://lnkd.in/gnUjN6Ai #OrganTransplant #Bioengineering #HOPEProgram #LifeSciences #HealthcareInnovation #WellcomeLeap