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Our research
We apply computational approaches to study how the immune system and particularly age-related immune decay affect general health, cancer development, progression and treatment response.
Our mission is to understand cancer-immune interaction and cancer evolution at the molecular level, and to build tools and develop methods that use this information to improve patient treatment.
Nicolai Birkbak has a background in cancer biology, biomarker development, translational cancer research and cancer evolution and heterogeneity based on research undertaken at TechnicalUniversity of Denmark (PhD and postdoc), Dana-Farber Cancer Institute (postdoc), and University College London & the Francis Crick Institute (senior postdoc).
Nicolai Juul Birkbak at Google Scholar
The thymus and immune health
The immune system undergoes profound changes throughout life, yet individuals age immunologically at remarkably different rates. This variation in immune decay, or immunosenescence, influence the body’s ability to respond to infection, prevent cancer, maintain tissue homeostasis, and recover from disease. Understanding why immune health declines in some individuals but is preserved in others is a central question in our research.
Our goal is to develop quantitative measures of immune health that can be integrated into clinical medicine. By combining artificial intelligence, medical imaging, population-scale cohorts, molecular profiling, and clinical data, we study how the immune system changes across the lifespan and how these changes influence health and disease. Our current work focuses on the thymus, a central immune organ responsible for generating new T cells. Although the thymus gradually involutes from early life, this process is highly heterogeneous, with some individuals maintaining thymic function for decades while others experience accelerated decline.
Our research has shown that preserved thymic health is associated with lower risk of cardiovascular disease, reduced cancer incidence, and improved overall survival. In patients with cancer, thymic health is also associated with response to immunotherapy, treatment-related toxicity, and clinical outcome. Together, these findings identify the thymus as a clinically relevant marker of immune health and provide a foundation for developing broader approaches to measure, understand, and ultimately preserve immune function throughout life.
Cancer evolution and immune health
Cancer develops through a continuous process of evolution, driven by the acquisition of genetic alterations and shaped by selective pressures within the host. Understanding how normal cells transform into invasive and metastatic disease remains a central challenge in cancer research and has been a long-standing focus of ourwork.
Advances in next-generation sequencing and large, clinically annotated patient cohorts have transformed our understanding of cancer genomes, revealing the evolutionary trajectories and molecular mechanisms that underlie tumour development. While these studies have identified many of the genetic alterations that drive cancer, they have also highlighted that tumour genetics alone cannot fully explain why cancers arise, progress, metastasize, or respond to treatment.
Our research therefore combines cancer genomics with immunosenescense and immune health. We investigate how variation in immune function influences cancer evolution, from early tumour suppression and immune surveillance to metastatic dissemination and response to therapy. This includes developing computational approaches to integrate molecular tumour profiling with quantitative measures of host immune health, allowing us to study the dynamic interaction between evolving cancer cells and the immune system.
By combining tumour-centric and host-centric perspectives, we aim to better understand the biological processes that determine cancer risk, disease progression, and treatment outcome, and to identify new opportunities for precision oncology.
Immune health biomarkers
A major goal of our research is to develop quantitative biomarkers that capture the functional state of the immune system. Unlike conventional biomarkers that focus on the tumour itself, our approach aims to measure the host immune system and its capacity to prevent disease, respond to therapy, and maintain long-term health.
Our current work focuses on biomarkers of thymic health and adaptive immune function. Together with Professor Aerts group at Harvard, we have used artificial intelligence applied to routine CT scans and developed imaging-based measures of thymic health that provide a non-invasive assessment of immune ageing at population scale. We complement these approaches with molecular measurements of thymic output, including T-cell receptor excision circles (TRECs), T-cell receptor repertoire diversity, and other immune profiling technologies to characterize immune competence from multiple perspectives.
By integrating imaging, molecular profiling, and clinical data across large patient cohorts, we investigate how immune health influences disease risk, cardiovascular health, cancer development, and treatment response. Ultimately, we aim to establish clinically accessible biomarkers that enable immune health to become a measurable component of precision medicine, supporting risk stratification,treatment selection, and disease prevention.
Software
Defining cGAS-STING activity in cancer
https://github.com/mxs3203/csg_prediction
Original publication: Classifying cGAS-STING activity links chromosomal instability with immunotherapy response in metastatic bladder cancer
GENIUS: Multiomics data analysis based on spatial transformation
https://github.com/mxs3203/genome_mapped_to_image
Original publication:GENIUS: GEnome traNsformatIon and spatial representation of mUltiomicS data
Group leader
