Researcher | Research Overview
Our goal is to understand the principles of how inflammation drives memory formation in human barrier tissues, in order to program and re-program them in disease. We are developing a training environment where we apply emerging techniques to answer fundamental questions of biological and clinical relevance in barrier tissue biology.
Conceptually, for a barrier tissue to effectively learn from previous immunological experiences, it can sense, adapt, and store this information (i.e. memory) in readily accessible permanent resident cell types. We are interested in exploring how memories of previous immune events (i.e. inflammatory memory) enables barrier tissues (airway, intestine, and skin) to recall diverse environmental exposures, informing future responses. We are particularly interested in further understanding our discovery that epithelial stem cells, amongst other parenchymal, stromal, neuronal, and immune cell subsets, can form inflammatory memory, raising the possibility of distributed memory formation.
Technically, we utilize single-cell RNA-sequencing (scRNA-seq), computational methods, organoid models, epigenetic profiling, flow cytometry, and microscopy applied to human health and disease. We then build testable models to explore with humans (organoids, treatment response vs. failure) or with mice (genetics, optogenetics, cellular immunology), towards the aim of improving disease understanding and treatment.
Our approach is to integrate immunological insights with innovative technologies, experimentation, and computational methods. Current projects in the lab focus on:
- Understanding human inflammatory diseases at single-cell resolution in barrier tissues (allergic inflammation, Crohn’s, colitis, psoriasis, eczema),
- Defining the mechanisms of inflammatory adaptation and memory by epithelial stem cells, and
- Building a framework for how inflammation changes the states of epithelial, stromal and immune cells to reshape their interactions.
If you have any idea that fits within these broad interests, please reach out!
Researcher | Research Background
Jose grew up in a Spanish household within the Boston area, attending high school in Framingham, MA, college at Tufts University, and graduate studies in the Harvard Immunology program. During his undergraduate, Jose worked in human immunology labs at Biogen Idec, University College London, and Boston Children's Hospital, where he focused on monogenic immune deficiencies. For his PhD work, Jose trained with Uli von Andrian, studying how the nervous system and the immune system function together as the principal sensory interfaces between the internal and external environments.
Seeking experimental approaches to return to the human system, he decided to gain first-hand experience in the nascent field of single-cell genomics to be able to work across multiple cell types in barrier tissues. As a Damon Runyon Postdoctoral Fellow in the Laboratory of Alex K. Shalek at MIT, the Broad, and the Ragon Institute, he began charting maps of human gut and airway, and discovered how human stem cells can be shaped by, and remember, inflammation. Jose started his group in 2019 at Boston Children's Hospital. He continues to be supported by a great team of undergraduate students, graduate students, technicians and colleagues, and looks forward to his lab integrating with the BCH community.