Alexandra-Chloé Villani, Ph.D.

Alexandra-Chloé Villani is an institute member of Broad Institute of MIT and Harvard, an assistant professor of medicine at Harvard Medical School, and a principal investigator at the Massachusetts General Hospital (MGH) Center for Cancer Research and at the Center for Immunology and Inflammatory Diseases (CIID), where she is also the director of the CIID Single Cell Genomics Research Program. 

The Villani Lab seeks to establish a comprehensive roadmap of the human immune system by achieving a higher resolution definition and functional characterization of cell subsets and rules governing human immune response regulation, as a foundation for deciphering how immunity is dysregulated in diseases. They are using single-cell “multi-omics” strategies, unbiased systems immunology approaches, and integrative computational frameworks empowering the study and modeling of the human immune system as a function of “healthy” and inflammatory states, disease progression, and response to treatment. 

The lab is also actively contributing to the Human Cell Atlas (HCA) Immune Bionetwork initiative, by charting at high resolution the human blood cellular landscape across 20 immune-related diseases. Their goal is to map all existing immune cell states with a frequency of at least ~0.1%. Additionally, they are studying paired human tissues with blood to better establish how circulating immune cells mirror those in the tissue microenvironment in the context of health and immune-related diseases. Villani co-leads the coordination of the HCA Immune Bionetwork and is a member of the HCA Organizing Committee. She is also the principal investigator of the HCA Cell Annotation Platform (CAP), through which they are developing a centralized open-source cell annotation platform to enable researchers to compare cell annotations within or across datasets, provide feedback on existing annotations, and collect annotations in an organized fashion to power machine learning approaches for automating annotation and deriving abstractions. 

Villani also leads a multi-disciplinary translational group of scientists and clinicians at MGH working towards achieving a better understanding of the biological players and underlying mechanisms involved in driving immune-related adverse events (irAEs) induced by immune-checkpoint inhibitor (ICI) therapy. The goal of this work is to improve cancer patient care and quality of life through identifying novel biomarkers and therapeutic targets that have the potential of mitigating irAE without reducing the efficacy of the immunotherapy. Collectively, through these HCA and translational efforts, Villani’s work ultimately seeks to develop a more comprehensive human immune lexicon that will be key to promoting effective bench-to-bedside translation of findings. 

Villani received a B.Sc. in physiology and a Ph.D. in experimental medicine from McGill University. Her doctoral research identified new susceptibility genes contributing to inflammatory bowel disease pathogeneses. She completed her postdoctoral training as a Banting Postdoctoral Fellow in the field of systems immunology and single-cell genomics at the Broad Institute, where she developed new systems immunology and single-cell genomics strategies that led to identifying five novel human blood immune cell populations. Her findings helped highlight the value of embarking on a comprehensive Human Cell Atlas initiative. She is the recipient of numerous honors, including the MGH Transformative Scholar in Medicine Award, the MGH Howard M. Goodman Fellowship, the Damon Runyon-Rachleff Innovation Award, the Melanoma Research Alliance Young Investigator Award, and the NIH Director’s New Innovator Award.