JOIN! Our group invents and applies protein engineering technologies to study fundamental functional principles of natural and artificial living systems at a cellular level.
We are seeking mechanistic explanations for how cells sense, integrate and exchange information, how pathologic changes in these processes relate to health and disease, and provide insights into new therapies.
Typical questions we ask are:
- What are the minimally required functional features of cellular components that regulate cellular homeostasis and signal transduction? How does their activity change during normal development?
- What are specific activity patterns associated with disease onset?
- How can cellular signaling systems be re-engineered for therapeutic purposes?
We answer these questions by inventing methods to observe, delineate and precisely control cellular physiology. Our approach employs techniques from multiple disciplines including optogenetics, electrophysiology, and rational protein design.
We collaborate extensively to apply our technologies to diverse problems in human health. For example, to recapitulate misregulation of specific ion channels and receptors in models of cardiovascular disorders, to reveal how specific cell types contribute to the different neural circuits that underlie cognition and behavior, and to establish clear correlations between specific changes in regulated cell signaling networks and molecular signatures of tumors enabling tumor proliferation and migration.
Next-Generation Neuromodulation Technology
We are developing novel optogenetic reagents that allow us to systematically perturb specific ion channels and signaling receptors in a time- and amplitude-variant manner. We combine these molecular reagents into an experimental framework in which all families of ion channels and receptors can be independently controlled, and their contribution to diverse cellular signal transduction circuits investigated.
Engineered Viral Tropism
The prevailing methods for genetic manipulation of tissue (e.g. for gene therapy) rely on viruses and genetic elements that restrict the expression of transgenes to defined sets of cells. In many ways these methods are limited in specificity, translational utility and payload capacity. Our agenda is to fundamentally change how cell-type specific genetic manipulation is achieved; to not rely on selective expression and focus on selective delivery instead. Accordingly, we are developing viral methods able to deliver genetic payloads to cells based on an user-defined tropism.
We gratefully acknowledge support from the Brain & Behavior Research Foundation.