Research

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:

Engineering programmable mammalian cell-based therapies
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.
Enabling design-driven engineering of living systems
We develop biotechnology platforms and computational tools that enable bioengineers to compose sophisticated biological programs in living cells. Realizing this vision of applying the design-build-test-learn paradigm to living cells requires advancing frontiers of synthetic biology to enable building, characterizing, and analyzing cellular functions. These efforts involve close, integrated collaboration between computational and experimental teams.
Understanding immune function and immunotherapies through systems biology
We seek to understand and therapeutically manipulate immune function, with a particular focus on 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.
Harnessing extracellular vesicles as therapeutic delivery vehicles
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 technologies enabling bioengineers to build customized EVs that serve as bespoke therapeutic delivery vehicles.
Probing and modulating bacterial metabolism via synthetic biosensors
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 bottom-up strategies for building metabolite-responsive transcriptional regulators.
MetabolicEngineering

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