(6ln) Molecular Engineering Approaches Towards Platform Immuno-Biomaterials

My vision is to create an independent research laboratory specializing in molecular engineering approaches towards creating platform immuno-biomaterials for medical application. More specifically, my research group will hybridize my expertise in nanomaterial development, soft matter creation, and immunology to address unmet needs in the biomaterials and drug delivery communities. Toward this end, three of the initial research projects from my group will involve the development of RNA nanomaterials for cancer immunotherapy applications, the engineering of shear-thinning soft material platforms to address autoimmune disorders, and the generation of anti-fibrotic hydrogels to evade the foreign body response.

The vision for my independent research laboratory was shaped by my experience as a NSF GRFP Ph.D. student and postdoctoral fellow in the laboratories of Professors Robert Langer and Daniel Anderson at the Massachusetts Institute of Technology. During my Ph.D. studies at the Massachusetts Institute of Technology, I gained expertise in nanomaterials science from the standpoints of material development, formulation, as well as in vitro and in vivo administration. More specifically, I employed molecular engineering approaches throughout my graduate work to create non-viral nanomaterials capable of delivering therapeutic RNAs (including messenger RNAs, short interfering RNAs, and antisense RNAs) to target cells within the body. Therapeutic RNAs can be used for a range of biomedical applications including genomic engineering, cancer immunotherapy, and protein replacement strategies. However, their serum instability, immunogenicity, and limited ability to passively transfect cellular membranes limits their clinical potential. Toward this end, our work explored how fundamental properties of RNA encapsulating nanomaterials (including size, encapsulation efficiency, zeta potential, and particle morphology) influenced the transport and biological mechanism of our nanomaterials to/within target cells in the liver, lung, and spleen. Further highlights of this work involved the development of patented nanotechnologies that are currently being pursued as lead delivery vectors for the treatment of human disease with a pharmaceutical partner.

After completing my Ph.D. studies, I remained in the laboratory of Professor Robert Langer at the Massachusetts Institute of Technology to develop expertise on the molecular engineering of soft matter for immunological research. To date, the most significant research contribution to my postdoctoral studies involved the development of an injectable hydrogel platform for the recruitment of specific immune cell populations to the site of injection. Further, my work also involved the molecular engineering and fabrication of a catalyst and initiator free hydrogel platform with tunable rheological properties for use in 3-dimensional cell culture and tissue engineering applications. We are also currently exploiting the scalability and batch consistency of this second hydrogel platform for biological additive manufacturing processes.

In sum, my future research vision is to create a molecular engineering laboratory that specializes in the creation of platform immuno-biomaterials exploiting concepts from nanomaterials development, soft matter creation, and immunology. In doing so, not only will we aim to better understand the fundamental underpinnings governing biological processes in the body, but we will also work towards the generation of translational technologies for the ultimate goal of treating human disease at the immunological level.

Teaching Interests:

1. Thermodynamics: This course will cover the fundamental principles of thermodynamics. Discussion surrounding how changes in temperature, the relationship between heat and work, and transformation of energy will be covered. Particular emphasis will be focused on the understanding of the fundamental underpinnings of thermodynamics with application towards comprehending combustion, fluid flow, and power generation. Select examples of chemical engineering approaches to understanding biological systems will also be provided to supplement representative in class examples exploring thermodynamic processes.
2. Introduction to Chemical Engineering: This course will cover the basic underpinnings of engineering through the analysis of physical and chemical processes. Material and energy balances, kinetics of chemical reactions, staged separations, and material balance will be covered. Current research trends including nanotechnology, biotechnology, and energy will also be discussed to highlight specific concepts from chemical engineering.
3. RNA delivery from concept to clinic: This course will cover the historical background, transport principles, and cutting-edge technologies associated with the local and systemic delivery of nucleic acid therapeutics. Proposed mechanisms of cellular uptake as well as the formulation and characterization of polymeric and nanoparticle based materials for non-viral RNA delivery will be discussed. Special units will focus on utilizing immune cell populations as antigen presenting cells and their potential role in developing cancer immunotherapy strategies.

Selected Relevant Publications (25 Total Published Manuscripts and 3 US Patents):

1. Fenton, O.S.; Tibbitt, M.W.; Appel, E.A.; Jhunjhunwala, S.; Webber, M.J.; Langer, R.* “Injectable Polymer-Nanoparticle Hydrogels for Local Immune Cell Recruitment”, accepted, Biomacromolecules, DOI: 10.1021/acs.biomac.9b01129.
2. Fenton, O.S.; Andresen, J.L.; Paolini, M.; Langer, R.* “B-Amino-acrylate Synthetic Hydrogels: Easily Accessible and Operationally Simple Networks for Biomaterials Application”, Angewandte Chemie, 2018, 57, 16026.
3. Fenton, O.S.; Olafson, K.N.; Pillai, P.; Mitchell, M.J.*; Langer, R.* “Advances in Biomaterials for Drug Delivery”, Advanced Materials, 2018, 30, 1705328.
4. Fenton, O.S.; Kauffman, K.J.; McClellan, R.L.; Kaczmarek, J.C.; Zeng, M.D.; Andresen, J.L.; Rhym, L.H.; Heartlein, M.W.; DeRosa, F.; Anderson, D.G.* “Customizable Lipid Nanoparticle Materials for the Delivery of siRNAs and mRNAs”, Angewandte Chemie, 2018, 41, 13582.
5. Fenton, O.S.; Kauffman, K.J.; Kaczmarek, J.C.; McClellan, R.L.; Jhunjhunwala, S.; Tibbitt, M.W.; Zeng, M.D.; Appel, E.A.; Dorkin, J.R.; Mir, F.; Yang, J.H.; Oberli, M.A.; Heartlein, M.W.; DeRosa, F.; Langer, R.; Anderson, D.G.* “Design and Synthesis of Ionizable Lipid Materials for the In Vivo Delivery of Messenger RNA to B Lymphocytes”, Advanced Materials, 2017, 29.
6. Fenton, O.S.; Kauffman, K.J.; McClellan, R.L.; Appel, E.A.; Dorkin, J.R.; Tibbitt, M.W.; Heartlein, M.W.; DeRosa, F.; Langer, R.; Anderson, D.G. “Bioinspired Alkenyl Amino Alcohol Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery”, Advanced Materials, 2016, 28, 2939-2943.

For a complete listing please see: https://scholar.google.com/citations?user=ZSSrYrMAAAAJ&hl=en