Joshua N. Leonard Associate Professor of Chemical and Biological Engineering

Research Interests

Engineering cellular systems and biomolecules for immunotherapy, synthetic biology, and biotechnology

Our group creates novel biological systems that perform customized, sophisticated functions for applications in biotechnology and medicine. Using the tools of synthetic biology, protein and biomolecule engineering, systems biology, and gene therapy, we develop technologies for manipulating and coordinating complex multicellular functions. A central area of interest for our group is controlling the function of a complex biological network, the human immune system, by engineering novel biomolecules and programmable cell-based “devices” to create novel, customized immune functions. By enabling clinicians to modify local immune responses in a patient- and disease-specific fashion, we are overcoming barriers to treatment for conditions ranging from cancer and chronic infections to autoimmune disease and transplant rejection. Other research themes include engineering coordinated microbial networks to create self-optimizing microbial consortia for applications in biotechnology, and developing platforms for synthetic interkingdom communication to create technologies such as symbiotic microbial biosensors that coordinate with human host cells. By bringing an engineering approach to the analysis, design, and construction of complex biological systems, we are advancing the frontiers of design-based medicine to address unmet medical needs and create safe, effective, and long-lasting treatment options that improve both quantity and quality of life.

Selected Publications

Engineering Modular Biosensors to Confer Metabolite-Responsive Regulation of TranscriptionYounger AKD, Dalvie NC, Rottinghaus AG, and Leonard JN. ACS Synthetic Biology. 2017 February 17;6(2):311-325.

Adding energy minimization strategy to peptide-design algorithm enables better search for RNA-binding peptides: Redesigned λ N peptide binds boxB RNA. Xiao X, Hung ME, Leonard JN, and Hall CK. Journal of Computational Chemistry. 2016 October 15;37(27):2423-2435.

A Platform for Actively Loading Cargo RNA to Elucidate Limiting Steps in EV-mediated DeliveryHung ME and Leonard JN. Journal of Extracellular Vesicles. 2016 May 13;5:31027.

Transforming growth factor-beta 1 delivery from microporous scaffolds decreases inflammation post-implant and enhances function of transplanted isletsLiu JMH, Zhang J, Zhang X, Hlavaty KA, Ricci CF, Leonard JN, Shea LD, and Gower RM. Biomaterials. 2016 February;80:11-19.

Regulation of Bacterial Gene Expression by Protease-Alleviated Spatial Sequestration (PASS). Pitner RA, Scarpelli AH, and Leonard JN. ACS Synthetic Biology. 2015 September 18;4(9):966-974.

Spatial and Functional Heterogeneities Shape Collective Behavior of Tumor-Immune Networks. Wells DK, Chuang Y, Knapp LM, Brockmann D, Kath WL, and Leonard JN. PLoS Computational Biology. 2015 April 23;11(4):e1004181.

Contributions of Unique Intracellular Domains to Switchlike Biosensing by Toll-like Receptor 4. Daringer NM, Schwarz KA, and Leonard JN. Journal of Biological Chemistry. 2015 April 3;290(14):8764-8777.

Stabilization of Exosome-targeting Peptides via Engineered GlycosylationHung ME and Leonard JN. Journal of Biological Chemistry. 2015 March 27;290(13):8166-8172.

Therapeutic Applications of Extracellular Vesicles: Clinical Promise and Open Questions. György B, Hung ME, Breakefield XO, and Leonard JN. Annual Review of Pharmacology and Toxicology. 2015 January;55:439-464.

Modular Extracellular Sensor Architecture for Engineering Mammalian Cell-based Devices. Daringer NM, Dudek RM, Schwarz KA, and Leonard JN. ACS Synthetic Biology. 2014 December 19;3(12):892-902.

Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype. Boehler RM, Kuo R, Shin S, Goodman AG, Pilecki MA, Leonard JN, and Shea LD. Biotechnology & Bioengineering. 2014 June;111(6):1210-1221.

Modulation of leukocyte infiltration and phenotype in microporous tissue engineering scaffolds via vector induced IL-10 expression. Gower RM, Boehler RM, Azarin SM, Ricci CF, Leonard JN, and Shea LD. Biomaterials. 2014 February;35(6):2024-2031.

FedExosomes: Engineering Therapeutic Biological Nanoparticles that Truly DeliverMarcus ME and Leonard JN. Pharmaceuticals. 2013 May;6(5):659-680.

TLR3-Specific Double-Stranded RNA Oligonucleotide Adjuvants Induce Dendritic Cell Cross-Presentation, CTL Responses, and Antiviral Protection. Jelinek I, Leonard JN, Price GE, Brown KN, Meyer-Manlapat A, Goldsmith PK, Wang Y, Venzon D, Epstein SL, and Segal DM. Journal of Immunology. 2011 February 15;186(4):2422-2429.

Staying on message: design principles for controlling nonspecific responses to siRNA. Samuel-Abraham S and Leonard JN. FEBS Journal. 2010 December;277(23):4828-4836.

View all publications by Joshua Leonard listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.