Our research directions are inspired by natural cellular communication mechanisms and focus on using biotechnology and molecular biology to enable therapeutic development primarily from completely biological materials.
Extracellular Vesicle (Exosome) Nanobiotechnology
Extracellular vesicles (EVs) - consisting of exosomes, microvesicles, and others - are secreted vesicles of cellular origin that comprise proteins, lipids, and RNAs and are thought to be critical mediators of intercellular communication. These vesicles can function as biological nanoparticles with abilities to cross biological barriers and evade immune response unmatched by any synthetic system. They can also be used in place of cell-based therapies where their drug-like qualities lend them significant advantages with regard to translation. However, the current translational potential of EVs is limited by biomanufacturing concerns as well as by a relative lack of control of cargo loading when compared to synthetic systems. Our group synergizes molecular characteristics of EVs with nanotechnology approaches to engineer novel nanobiotherapeutics for multiple applications. We are also interested in uncovering more about the fundamental role of EVs in intercellular communication.
- Patel DB; Luthers CR; Lerman MJ; Fisher JP; Jay SM. (2018) Enhanced extracellular vesicle production and ethanol-mediated vascularization bioactivity via a 3D-printed scaffold-perfusion bioreactor system. Acta Biomaterialia. Featured in special issue: Cell and Tissue Biofabrication
- Xu J; Feng Y; Conn O; Jeyaram A; Jay SM; Zou L; Chao W. (2018) Circulating plasma extracellular vesicles from septic mice induce inflammation via miRNA- and TLR7-dependent mechanisms. Journal of Immunology 201(11):3392-3400.
- Patel DB; Santoro M; Born LJ; Fisher JP; Jay SM. (2018) Towards Rationally Designed Biomanufacturing of Therapeutic Extracellular Vesicles: Impact of the Bioproduction Microenvironment. Biotechnology Advances. 36(8):2051-9.
- Lamichhane TN; Jay SM. (2018) Production of Extracellular Vesicles Loaded with Therapeutic Cargo. Methods in Molecular Biology 1831:37-47.
- Adams KR; Chauhan S; Patel DB; Clements VK; Wang Y; Jay SM; Edwards NJ; Ostrand-Rosenberg S; Fenselau C. (2018) Ubiquitin conjugation probed by inflammation in MDSC extracellular vesicles. J Proteome Res 17(1):315-324.
- Jeyaram A; Jay SM. (2017) Preservation and storage stability of extracellular vesicles for therapeutic applications. AAPS Journal 20(1):1.
- Lamichhane TN; Leung CA; Douti LY; Jay SM. (2017) Ethanol Induces Enhanced Vascularization Bioactivity of Endothelial Cell-Derived Extracellular Vesicles via Regulation of MicroRNAs and Long Non-Coding RNAs. Scientific Reports 7(1):13794.
- Li L; Jay SM; Wang Y; Wu SW; Xiao Z. (2017) IL-12 stimulates CTLs to secrete exosomes capable of activating bystander CD8+ T cells. Scientific Reports 7(1):13365.
- Jay SM; Vunjak-Novakovic G. (2017) Extracellular Vesicles and their Versatile Roles in Tissue Engineering. Tissue Engineering Part A 23(21-22):1210-1211.
- Patel DB; Gray KM; Santharam Y; Lamichanne TN; Stroka KM; Jay SM. (2017) Impact of Cell Culture Parameters on Production and Vascularization Bioactivity of Mesenchymal Stem Cell-Derived Extracellular Vesicles. Bioengineering and Translational Medicine 2(2):170-179.
- Lamichhane TN; Jeyaram A; Patel DB; Parajuli B; Livingston NK; Arumugasaamy N; Schardt JS; Jay SM. (2016) Oncogene Knockdown via Active Loading of Small RNAs into Extracellular Vesicles by Sonication. Cellular and Molecular Bioengineering Sep;9(3):315-324.
- Lamichhane TN; Raiker RS; Jay SM. (2015) Exogenous DNA Loading into Extracellular Vesicles via Electroporation is Size-Dependent and Enables Limited Gene Delivery. Molecular Pharmaceutics Oct 5;12(10):3650-7.
- Lamichhane TN; Sokic S; Schardt JS; Raiker RS; Lin JW; Jay SM. (2015) Emerging roles for extracellular vesicles in tissue engineering and regenerative medicine. Tissue Engineering Part B Feb;21(1):45-54.
We are interested in designing and developing proteins as therapeutics and drug delivery vehicles. An example is the development of novel multivalent ligands of the ErbB family of receptors, which play prevalent roles in numerous biological processes such as vascularization and cancer. These engineered proteins are capable of inducing specific receptor interactions that lead to therapeutic benefit in various settings, including cardiovascular toxicity and cancer. We continue to utilize protein engineering and design for a variety of purposes, including non-coding RNA delivery, and have interest in applying these approaches to therapeutic applications in wound healing, vascularization, cancer, and more.
- Schardt JS; Noonan-Shueh M; Oubaid JM; Pottash AE; Williams SC; Hussain A; Lapidus RS; Lipkowtiz S; Jay SM. (2019) HER3-targeted affibodies with optimized formats reduce ovarian cancer progression in a mouse xenograft model. AAPS Journal. 21(3):48.
- Pottash AE; Kuffner C; Noonan-Shueh M; Jay SM (2019) Protein-based Vehicles for Biomimetic RNAi Delivery. Journal of Biological Engineering. 13:19. Featured in special issue: Emerging Leaders in Biological Engineering
- Schardt JS; Williams SC; Howard JL; Aloimonos CM; Bookstaver ML; Lamichhane TN; Sokic S; Liyasova MS; Hussain A; Lipkowitz S; Jay SM (2017) Engineered Multivalency Enhances Affibody-Based HER3 Inhibition and Downregulation in Cancer Cells. Molecular Pharmaceutics. Apr 3;14(4):1047-1056.
Gene and Drug Delivery
In addition to drug and nucleic acid delivery using exosomes and other extracellular vesicles, we are interested in developing biomaterial-based delivery systems for a variety of applications. We are especially interested in nucleic acid and protein delivery via biopolymer-based systems (e.g. alginate, chitosan, etc.), but also have interest and experience with lipid and synthetic polymer formulations.
- Kuwahara G; Hashimoto T; Tsunami M; Yamamoto K; Assi R; Foster TR; Hanisch JJ; Bai H; Hu H; Protack CD; Hall MR; Schardt JS; Jay SM; Madri JA; Kodama S; Dardik A. (2017) CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation. Arterioscler Thromb Vasc Biol. Jun;37(6):1147-1156.
We are grateful to the following agencies/institutions/companies for generously supporting our work: