Develops computational methods to study the epigenetic regulation of gene expression and its implications in important human conditions including aging and common diseases.
Develops computational methods to study the epigenetic regulation of gene expression and its implications in important human conditions including aging and common diseases.
Aging impacts everyone, but its progression and effects vary greatly between individuals, influencing both healthspan and lifespan due to factors including biological sex and obesity. Our lab uses advanced systems immunology and single-cell biology to study how aging alters the genomics and functionality of human immune cells and diminishes vaccine effectiveness. Vaccine effectiveness declines with age, yet the biological mechanisms behind this drop remain poorly understood. By investigating immune responses to various vaccines in older adults and applying cutting-edge genomics and functional immunology, we seek to rejuvenate immune function and pave the way for precision medicine, ultimately improving immune health and responses for aging populations.
Recent publications
• Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults. Nature Immunology. 2024;25(2):316-29. PMID: 38182669.
• Transcriptional activation of Jun and Fos members of the AP-1 complex is a conserved signature of immune aging that contributes to inflammaging. Aging Cell;e13792. February 2023.
• Sexual dimorphism in human immune system aging. Nature Communications. February 2020. 11 (1), 1-17.
The regulation of gene expression programs in a cell, and ultimately its functionality, is influenced by both the genome and epigenome—chemical modifications that control how genes are turned on or off. Disruptions to these regulatory programs, whether caused by aging, genetic mutations, or environmental factors, can lead to cellular dysfunction and disease. Our lab generates and analyzes detailed maps of epigenetic changes in primary human cells. These maps help us understand how gene regulation is altered in disease and link these changes to genetic or environmental triggers, providing insights into disease mechanisms and uncover potential therapeutic targets.
Recent publications
• Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer. Nature Aging. 2024.
• Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights. Cell Metabolism. 2024. 36 (11), 2468-2488. e7 PMID: 39383866.
• Epigenetic memory of COVID-19 in innate immune cells and their progenitors. Cell. 2023 186(18). 3882-3902. PMID: 37597510.
New genomics technologies, such as next-generation sequencing and single-cell profiling, offer an unprecedented, detailed view of human cells. However, analyzing and integrating these complex datasets is computationally challenging. Our lab develops innovative computational methods, using approaches like network theory and machine learning, to effectively analyze these data. This allows us to uncover new insights into gene regulation and cellular behavior and inform us about human biology.
By combining cutting-edge genomics with state-of-the-art computational biology, our lab bridges fundamental science and practical applications. We aim to understand immune system aging and complex diseases at an individual level, ultimately driving personalized approaches to human health. Our long-term goal is to develop strategies to combat or even reverse age-related disorders, improving health and well-being for all.
Recent publications
• CoRE-ATAC: A Deep Learning model for the functional Classification of Regulatory Elements from single cell and bulk ATAC-seq data. PLOS Computational Biology. 2021. 17 (12). e1009670.
• AMULET: a novel read count-based method for effective multiplet detection from single nucleus ATAC-seq data. Genome Biology. 2021. 1. 1-19.
• A Bias-free Transcription Factor Footprint Enrichment Test. Nucleic Acids Research. 2019, Vol. 47, No. 2 e11.
Principal Investigator
