Our group is studying how cells interact to generate complex physiology in the human body, and how this changes over the lifespan of individuals and give rise to disease. To do that, we develop and employ computational methods for the analysis of spatial data (spatial transcriptomics, highly multiplexed imaging), its integration with various modalities of molecular data such as transcriptomics, proteomics, metabolomics, and importantly, clinical data of individuals along their lifespan. We aim to establish a link between the molecular activity of cells, the emergence of higher-order patterns of tissue organization, and the onset of disease. Questions that fuel our research are: How can we robustly define tissue architecture patterns across tissues and organs? Are there yet unknown recurrent tissue architecture patterns characteristic of health and disease? Can some patterns of tissue architecture condition therapy accessibility and treatment response? What are the large-scale patterns of immune cell distribution between and within organs? Can we define tissue integrity across the human body and measure it across the human lifespan? What is the relationship between tissue integrity, aging, and the onset of disease?
Computational pathology and tissue micro-anatomy
The spatial organization of tissue in micro-anatomical domains and their physical properties such as cell size, shape and organization, as well as extracellular matrix composition can change with pathology. Recent development of technologies such as multiplexed imaging and spatial transcriptomics allow for direct observation of both cellular phenotypes and cellular interactions in native tissue microenvironment. We aim to employ these technologies to uncover the organizing principles of human tissue architecture and organ-specific physiology. Advances in this area could enable the definition of tissue integrity in healthy human tissue across ages, detection of early pre-cancerous lesions and cancer invasion, and the study of age-associated diseases characterized by cellular degeneration and loss of tissue integrity.
Aging and lifespan extension
Aging is associated with conditions that impair quality of life, and represents one of the biggest current challenges in science. We hypothesize that previously unappreciated patterns of tissue organization may be related with either the origin or manifestation of loss of cell identity and tissue integrity associated with aging. Such patterns may not be randomly organized in the scale of human organs but may arise in particular spatial contexts related for example to the proximity to anatomical structures, extracellular matrix composition, or local patterns in metabolic activity, that cause inflammation, cellular senescence, and loss of tissue integrity characteristic of the aging process. We aim to understand the relationships between tissue integrity, aging, and disease onset, in order to propose interventions that can delay or stop the aging process, prevent disease onset, and expand the lifespan of individuals.