Current Research and Scholarly Interests
I seek to understand how mammalian cells process information and make decisions. This is a fundamental open question as cells are controlled by multiple signaling pathways with tens of signaling proteins, second messengers and chromatin modifiers connected to each other on time-scales of seconds to days by positive and negative feedbacks. Understanding how signaling circuits control cell proliferation, migration and other outputs is important for identifying optimal drug targets and to facilitate the development of combination therapies. Much of my work is built on the premise that genetic and biochemical methods can be used to identify and characterize components of signaling circuits, but that single-cell microscopy, live-cell signaling reporters, and rapid perturbations are needed to understand the design principles of signaling circuits. My laboratory has pioneered the development and use of molecular tools and quantitative microscopy methods to understand feedback-connected signaling circuits and made key contributions to our understanding of the spatial and temporal control of calcium, lipid second messenger, small GTPase, and protein kinase signaling processes. Our current research identifies general control principles and specific mechanisms how cells integrate receptor, cell contact and stress inputs to decide between quiescence, proliferation and senescence, how they switch metabolic states, and how they trigger polarization and decide to move. We are investigating these signaling circuits by combining high-resolution live-cell analysis of signal transduction and local chromatin activity with optogenetic perturbations, single-cell RNAseq and computational modeling.
