The mission of our lab is to learn how phagocytes across phyla recognize, internalize, and digest their targets and to use these insights to develop synthetic immune receptors for therapeutics. We strive to nurture an inclusive and curiosity-driven environment that empowers undergraduate student researchers to make substantive contributions to science. Our current studies use cellular and biochemical methods to uncover ancient mechanisms of immunity, with an emphasis on active, anti-inflammatory processes that promote development and repair of the nervous system.
Our reconstitution studies of phagocytosis also serve as a model to study general challenges facing immune cells:
(1) How to evolve a receptor repertoire that recognizes a diversity of self- and non-self ligands while minimizing autoimmunity
(2) How to integrate chemical and physical information to guide cellular decisions
(3) How to promote physiology by functioning in a manner exquisitely sensitive to tissue and context
PROTECTIVE CLEARANCE IN HEALTH AND DISEASE
The prompt recognition, internalization and digestion of apoptotic cells, synapses, and axonal fragments by phagocytes is required to maintain homeostasis during early development and adulthood. Executing these processes in a regulated and anti-inflammatory fashion requires extensive orchestration of a collection of activities including receptor-mediated phagocytosis, lysosome formation, and intracellular degradation. Protective clearance plays a particularly important role in maintaining function and homeostasis in the central nervous system (CNS) and sustained inflammation is linked to several neurodegenerative diseases. A key goal of our lab is to define the molecular mechanisms underlying protective clearance in endogenous phagocytes and to use these insights to understand the fundamental biology of diseases that impact the CNS.
CELLULAR EATING MACHINES FOR THERAPEUTICS
Programming phagocytes to eat targets they do not normally ingest (e.g. cancer cells) is an emerging area of interest in the field of immunotherapy. We are currently developing new chimeric antigen receptors for phagocytosis (CAR-Ps) that program macrophages to eliminate potentially harmful debris in an anti-inflammatory manner. Specifically, we use endogenous immune receptors as inspiration to build next generation CAR-Ps that promote phagocytosis of debris in a manner that protects sensitive surrounding tissue.
MECHANOBIOLOGY OF PHAGOCYTOSIS
Cells and organisms exist in dynamic physical environments subject to changes in temperature, viscosity, stiffness, and other properties over time scales ranging from fractions of a second to decades. How living systems use physical cues from their environments to instruct physiology and behavior is a central focus of mechanobiology, an emerging cross-disciplinary field that integrates biophysics, engineering, and materials science. As a result of their travels throughout the organism, macrophages navigate diverse environments that vary in physical properties across orders of magnitude. We are using a suite of biomechanical reconstitution methods to understand how phagocytes use physical information to decide what to eat.
