Chemical and Biological Engineering

Lonnie D. Shea

Professor of Chemical and Biological Engineering

Education

Ph.D. Chemical Engineering and Scientific Computing, University of Michigan, Ann Arbor, MI

M.S. Chemical Engineering, Case Western Reserve University, Cleveland, OH

B.S. Chemical Engineering (summa cum laude), Case Western Reserve University, Cleveland, OH

Research Interests

Systems and strategies for promoting tissue growth provide enabling technologies for either enhancing regeneration for diseased or injured tissues, or to investigate abnormal tissue formation such as cancer. Given the complexity inherent in tissues, the Shea laboratory is focusing on an approach termed "Systems Tissue Engineering", which indicates the need to develop systems capable of presenting combinations of factors that drive tissue growth, as well as the need to incorporate systems biology approaches that can identify the appropriate combination of factors. A central component of many approaches involves biomaterials, which provide a tool by which to create an environment and/or deliver factors that can direct cellular processes toward tissue formation.  Biomaterial scaffolds are developed that present signals in the form of adhesive proteins, mechanical properties, growth factors, hormones, and cytokines. This potential of presenting multiple cues to target multiple aspects of tissue formation is applied to islet transplantation for diabetes therapy, ovarian follicle maturation to preserve fertility for women and girls facing a cancer diagnosis, and spinal cord regeneration to treat paralysis. In these approaches, the environment must be created that provides factors to stimulate growth and also blocks factors that inhibit regeneration. More recently these scaffolds have been applied to the early detection of cancer by creating an environment that can capture metastatic cancer cells. Furthermore, nanoparticles have recently been applied for modulating the immune response, in order to the induction of tolerance in autoimmune disease

The ability to present multiple factors raises the challenge of identifying the combination that will maximally promote tissue formation. Toward this goal, we have developed a cellular array for the large scale profiling of transcription factor activity throughout tissue formation, which we propose can identify the factors necessary to drive cells towards the desired phenotype. This array represents a novel systems biology tool for molecularly dissecting tissue formation. This approach of relating tissue development to molecular design of the scaffold may ultimately lead to the formation of engineered tissues that could provide alternatives to whole organ or tissue transplantation.

Selected Publications

• Shepard, J. A.; Shea, L. D.; Shin, S.; Virani, F. R.; Goodman, A. G., “Hydrogel macroporosity and the prolongation of transgene expression and the enhancement of angiogenesis”, Biomaterials, (2012)
• M. S. Weiss, B. P. Bernabe, A. Shikanov, D. A. Bluver, M. D. Mui, S. Shin, L. J. Broadbelt and L. D. Shea, “The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells”, Biomaterials, (2012)
• D. Tagler, T. Tu, R. M. Smith, N. R. Anderson, C. M. Tingen, T. K. Woodruff and L. D. Shea, “Embryonic Fibroblasts Enable the Culture of Primary Ovarian Follicles Within Alginate Hydrogels”, Tissue Engineering Part a, (2012)
• others; Holland, S. J.; Tuinstra, H. M.; Zelivyanskaya, M. L.; Shin, S., “Bridges delivering neurotrophin encoding lentivirus enhance regeneration following spinal cord injury”, Biomaterials, (2011)
• R. F. Gibly, X. Zhang, M. L. Graham, B. J. Hering, D. B. Kaufman, W. L. Lowe, Jr. and L. D. Shea, “Extrahepatic islet transplantation with microporous polymer scaffolds in syngeneic mouse and allogeneic porcine models”, Biomaterials, (2011)
• R. F. Gibly, J. G. Graham, X. Luo, W. L. Lowe, Jr., B. J. Hering and L. D. Shea, “Advancing islet transplantation: from engraftment to the immune response”, Diabetologia, (2011)
• Jaclyn A. Shepard;Paul J. Wesson;Christine E. Wang;Alyson C. Stevans;Samantha J. Holland;Ariella Shikanov;Bartosz A. Grzybowski;Lonnie D. Shea, “Gene therapy vectors with enhanced transfection based on hydrogels modified with affinity peptides”, Biomaterials, (2011)
• A Shikanov;RM Smith;M Xu;TK Woodruff;LD Shea, “Hydrogel network design using multifunctional macromers to coordinate tissue maturation in ovarian follicle culture”, Biomaterials, (2011)
• Taba Kheradmand;Shusen Wang;Romie F. Gibly;Xiaomin Zhang;Samantha Holland;James Tasch;Jack G. Graham;Dixon B. Kaufman;Stephen D. Miller;Lonnie D. Shea;Xunrong Luo, “Permanent protection of PLG scaffold transplanted allogeneic islet grafts in diabetic mice treated with ECDI-fixed donor splenocyte infusions”, Biomaterials, (2011)
• AD Bellis;B Penalver-Bernabe;MS Weiss;ME Yarrington;MV Barbolina;AK Pannier;JS Jeruss;LJ Broadbelt;LD Shea, “Cellular Arrays for Large-Scale Analysis of Transcription Factor Activity”, Biotechnology and Bioengineering, (2011)
• Shea, L. D.; Xu, M.; Woodruff, T. K.; Hirshfeld-Cytron, J. E.; Jozefik, J. K., “Animal age, weight and estrus cycle stage impact the quality of in vitro grown follicles”, Human Reproduction, (2011)
• Shea, L. D; Schaffer, D. V; Jang, J. H, “Engineering Biomaterial Systems to Enhance Viral Vector Gene Delivery”, Molecular Therapy, (2011)
• Shea, L. D; Zhang, Z.; Shikanov, A.; Xu, M.; Smith, R. M, “Fibrin encapsulation and VEGF delivery promotes ovarian graft survival in mice”, Tissue Engineering, (2011)
• TK Woodruff;LD Shea, “Ovarian Rigidity Regulates Follicle Function and Egg Quality”, Biology of Reproduction, (2010)
• Michael S Weiss;Beatriz Penalver Bernabe;Abigail D Bellis;Linda J Broadbelt;Jacqueline S Jeruss;Lonnie D Shea, “Dynamic, large-scale profiling of transcription factor activity from live cells in 3D culture”, PloS one, (2010)
• SJ SHIN;HM TUINSTRA;DM SALVAY;LD SHEA, “Phosphatidylserine immobilization of lentivirus for localized gene transfer”, Biomaterials, (2010)
• S SHIN;LD SHEA, “Lentivirus Immobilization to Nanoparticles for Enhanced and Localized Delivery From Hydrogels”, Molecular Therapy, (2010)
• ... Huang, ER West, M Zelivyanskaya, LD Shea, “Spatially patterned gene expression for guided neurite extension”, J Neurosci Res, (2009)
• L DE LAPORTE, Y YANG, ML ZELIVYANSKAYA, et al., “Plasmid Releasing Multiple Channel Bridges for Transgene Expression After Spinal Cord Injury”, MOLECULAR THERAPY, (2009)