Laboratory for Cellular Devices and Biomolecular Engineering
The Leonard Lab is committed to enabling an emerging paradigm of design-driven medicine by integrating synthetic biology with systems biology to address pressing challenges in medicine and biotechnology. Our long-term areas of interest include:
Mammalian Synthetic Biology
We are pioneering the design of novel cell-based devices that can be programmed to manipulate and detect changes in human physiology. This approach promises to transform our ability to implement customizable therapeutic and diagnostic strategies, to address unmet medical needs, and ultimately to create safe, effective, and long-lasting therapeutic benefits for a wide variety of diseases.
Systems Biology of Immune Function
We seek to understand and therapeutically manipulate interactions that occur between the immune system and cancer. Tumors establish dysfunctional immunological microenvironments which pose a barrier to therapeutic intervention. We use quantitative experimental methods and computational modeling to both understand how these complex multicellular networks operate and to design therapeutic strategies that can correct dysfunctional network states.
Engineering Novel Biomolecular Therapies
Recent evidence has established that all cells exchange biomolecules via lipid nanovesicles known as exosomes or extracellular vesicles (EVs). EV-mediated delivery of RNA and protein results in functional modulation of the recipient cell, which can alter disease processes in vivo and may be harnessed to deliver biomolecules for therapeutic applications. We develop methods to probe and manipulate the steps of cargo packaging into EVs and to achieve EV-mediated delivery of cargo to target cells.
Bacterial Synthetic Biology and Metabolic Engineering
In efforts to engineer microbial factories, screening and optimizing metabolic pathways remain rate-limiting steps. Metabolite-responsive biosensors may help to address these persistent challenges by enabling the monitoring of metabolite levels in individual cells and the implementation of metabolite-responsive feedback control. Given the limited pool of naturally-evolved biosensors, we are pioneering a bottom-up strategy for converting metabolite-binding proteins into metabolite-responsive transcriptional regulators.