Roberto Weigert, Ph.D.

Neutrophils in action during inflammation in vivo

Cancer initiation and early tumor evolution are dynamic processes that unfold within complex, living tissues. Conventional cell culture and endpoint analyses have provided essential mechanistic insights, but they cannot fully capture how cell behavior changes over time or how epithelial, immune, stromal, and extracellular-matrix components interact in their native environment. To address these limitations, our laboratory has developed a suite of intravital microscopy approaches that enable longitudinal imaging of the same tissue or lesion over time and observation across multiple biological scales—from tissue and single-cell behavior to subcellular processes and, most recently, individual molecules in living animals. These technologies are complemented by pharmacological, molecular, and genetic perturbations, quantitative image analysis, and AI-assisted methods for segmenting and analyzing complex three-dimensional living tissues.

This research program grew from our studies of membrane remodeling in epithelial and immune cells. Using exocrine glands in live rodents, we investigated how the actin cytoskeleton, cell signaling, and mitochondrial bioenergetics are coordinated during regulated exocytosis and plasma-membrane remodeling. In parallel, tumor and immune-cell models allowed us to examine how small GTPases, actin dynamics, signaling pathways, and cellular metabolism regulate cell migration, invasion, and interactions with the surrounding tissue. More recently, we have expanded this work to investigate how changes in cell-surface glycans influence membrane trafficking, adhesion, and cell behavior. Together, these studies established the conceptual and technological foundation for examining cellular and molecular processes directly within intact tissues.

Our current research applies these multiscale imaging approaches to cancer initiation and premalignancy, with a particular focus on experimental models of oral and head and neck cancer. We investigate how dynamic interactions among epithelial cells, immune populations—particularly neutrophils, macrophages, and other myeloid cells—and the surrounding tissue microenvironment shape immune surveillance, immune evasion, and tumor evolution. We are also examining how metabolic changes, glycan remodeling, stromal responses, and alterations in the extracellular matrix contribute to the transition from premalignant lesions to invasive disease.

By repeatedly imaging individual lesions and integrating these longitudinal observations with multiplex tissue imaging, spatial multi-omics, and AI-enabled quantitative analysis, we seek to connect dynamic cell behavior with underlying molecular states. The overall goal is to identify the early cellular interactions and tissue changes that determine lesion fate, predict malignant progression, and reveal potential opportunities for cancer interception.

Dr. Weigert obtained his B.Sc. in chemistry in 1992 from the University of Catania (Italy). He joined the Department of Cell Biology at the Mario Negri Institute (Dr. Alberto Luini) and in 2000 he received his Ph.D. from the Open University of London. In 2001, Dr. Weigert joined the NHLBI at NIH, as a research fellow in the Laboratory of Cell Biology (Dr. Julie Donaldson). In 2006, he joined the NIDCR as chief of the Intracellular Membrane Trafficking Unit, and he was tenured in 2014. In 2015, Dr. Weigert joined the Laboratory of Cellular and Molecular Biology at the NCI. In 2020, he established the CCR-NCI Intravital Microscopy Core and was appointed Deputy Chief in 2024. Currently Dr. Weigert serves as Acting Chief .