The Morgan lab invented a new method to grow living cells in three dimensions (3D) and is using this technology to answer fundamental questions in 3D tissue engineering, 3D cell-cell mechanics and 3D drug transport. These areas are relevant to important medical needs including the shortage of organs for transplantation, the lack of effective treatments for fibrosis, multi-drug resistance in cancer and the quest to find new and less toxic drugs while reducing the use of animals in research.

The Morgan lab has devised a new method for culturing cells in three dimensions (3D) and is using this technology to answer fundamental questions in three synergistic areas: 3D tissue engineering , 3D cell-cell mechanics and 3D drug transport . These areas are relevant to important medical needs including the shortage of organs for transplantation, the lack of effective treatments for fibrosis, multi-drug resistance in cancer and the quest to find new and less toxic drugs while reducing the use of animals in research. It has been widely recognized that cells cultured in 2D do not adequately mimic native tissues and organs and in recent years the field of tissue engineering has developed new methods for growing cells in 3D. The Morgan lab invented the 3D PetriDish®, now commercially available Microtissues, Inc (Sigma-Aldrich) to grow cells in 3D using micro-molded agarose gels. Unlike most methods in tissue engineering that attach cells to a scaffold, cells attach to each other in the 3D PetriDish®. Cells are seeded into micro-molded nonadhesive agarose gels where they self-assemble 3D multi-cellular microtissues of varying sizes and shapes from simple spheroids to more complex honeycomb structures in typically 24 hours. Like native tissue, cell density is high and cell-cell interactions such as mechanics and signaling are maximized. The Morgan Lab as well as many others has shown that this platform technology works for many different cell types including primary cells, cancer cell lines and stem cells.

In 3D tissue engineering , the Morgan lab has shown that micro-molds can produce microtissues in complex shapes such as toroids and honeycombs and that these microtissues will fuse to one another when placed in close contact. These structures with their open lumens that mimic an element of the vasculature are intriguing and we are investigating whether these microtissues can be used as building blocks to fabricate larger tissues and eventually organs.

In 3D cell-cell mechanics , the Morgan lab is making microtissues with various shapes such as loop ended dogbones, rods, and toroids-on-cones to investigate the mechanical forces that cells exert on one another in the context of a 3D multi-cellular microtissue. We have used the toroid-on-cone assay to quantify the work performed by a multi-cellular toroid as it contracts up the cone and shown that mixtures of fibroblasts and hepatocytes exert surprisingly high levels of force; a result relevant to fibrosis.

In 3D drug transport , the Morgan lab is using 3D spheroids to quantify the uptake and diffusion of various drugs through the multiple layers of cells as well as the role of drug efflux pumps that pump drugs out of cells. Drug transport is of fundamental importance to the efficacy and toxicity of all drugs and so is of great interest to the pharmaceutical industry. Moreover, some of these efflux pumps are upregulated in cancer which can lead to multi-drug resistance, an important clinical problem in need of new and more effective inhibitors.

National Institute of Health
National Science Foundation
Industry

Blakely, A.M., Manning, K.L., Tripathi, A. and Morgan, J.R. Bio-Pick, Place and Perfuse: A New Instrument for 3D Tissue Engineering. Tissue Eng. In Press.

Curran, S., Achilli, T-M, Leary, E., Wilks, B., Vantangoli, M.M., Boekelheide, K., and Morgan, J.R. A 3D Spheroid System to Evaluate Inhibitors of the ABCG2 Transporter in Drug Uptake and Penetration. TECHNOLOGY 3: 54-63, 2015

Achilli, T-M, McCalla, S., Meyer, J., Tripathi, A., Morgan, J.R. Multilayer Spheroids to Quantify Drug Uptake and Diffusion in 3D. Molecular Pharmaceutics, 11: 2071-2081, 2014. PMCID# PMC4096226

Svoronos, A. A., Tejavibulya, N., Schell, J.Y., Shenoy, V.B. and Morgan, J.R. Micro-mold Design Controls the 3D Morphological Evolution of Self-assembling Multi-cellular Microtissues. Tissue Eng. 20: 1134-1144, 2014.

Wang, H., Svoronos, A. A., Boudou, T., Chen, S. C., Morgan, J.R, and Shenoy V.B. Necking and Failure of Constrained Contractile 3D Microtissues: Role of Geometry and Stiffness. Proc. Nat'l. Acad. Sci. USA. 110(52): 20923-20928, 2013.

Desroches, B.R., Zhang, P., Choi, B., Maldonado, A.E., Rago, A., Liu, G.X. Nath, N., King, M.E., Hartmann, K.M., Yang, B., Koren, G., Morgan, J.R. and Mende U. Functional Scaffold-free Cardiac Microtissues: A Novel Model for the Investigation of Heart Cells. Am J Physiol. Heart Circ. Physiol 302: H22031-H220442, 2012.

Youssef, J., Chen, P., Shenoy, V.B. and Morgan, J.R. Mechano-Transduction is Enhanced by the Synergistic Action of Heterotypic Cell Interactions and TGF-B1. FASEB J. 26: 2522-2530, 2012. PMID: 22375018 [PubMed - as supplied by publisher].

Ho, D.N., Kohler, N., Sigdel, A., Killuri, R., Morgan, J.R., Xu, C., Sun, S.S. Penetration of Endothelial Cell Coated Multicellular Tumor Spheroids by Iron Oxide Nanoparticles. Theranostics. 2: 66-75, 2012. PMCID: PMC3263517.

Achilli, T-M., McCalla, S., Tripathi, A. and Morgan, J.R. Quantification of the Kinetics and Extent of Self-sorting in Three Dimensional Spheroids. Tissue Eng. 18: 302-309, 2012. PMCID: PMC3312373.

Bao, B.A., Lai, C.P.K., Naus, C.C., and Morgan, J.R. Pannexin 1 Drives Multicellular Compaction Via a Signaling Cascade that Upregulates Cytoskeletal Function. J. Biol Chem. 287: 8407-8416, 2012. PMCID: PMC3318751.

Tejavibulya, N., Youssef, J., Bao, B., Ferruccio, T-M and Morgan, J.R. Directed Self-Assembly of Large Scaffold-free Multi-cellular Honeycomb Structures. Biofabrication 3, 1-9, 2011. PMCID: PMC3176969.

Youssef, J., Nurse, A., Freund, L.B. and Morgan, J.R. Quantification of the Forces Driving Self-assembly of 3D Micro-tissues. Proc. Nat'l. Acad. Sci. USA. 108: 6993-6998, 2011. PMCID: PMC3084067.

Bao, B., Jiang, J. Yanase, T., Nishi, Y., and Morgan, J.R. Connexon-mediated Cell Adhesion Drives Microtissue Self-assembly. FASEB J. 25: 255-264, 2011. PMCID: PMC3005422.

Robins, J.C., Morgan, J.R., Krueger, P. Carson, S.A. Bioengineering Anembryonic Human Trophoblast Vesicles. Reproductive Sciences 18: 128-135, 2011. PMID: 20978180.

Krotz, S.F., Robins, J.C., Ferruccio, T-M., Moore, R., Steinhoff, M.M., Morgan, J.R. and Carson, S. In Vitro Maturation of Oocytes via Pre-fabricated Self-assembled Artificial Human Ovary. J. of Assisted Reproduction and Genetics.27: 743-750, 2010. PMCID: PMC2997950.

Livoti, C.M., and Morgan, J.R. Self-Assembly and Tissue Fusion of Toroid-Shaped Minimal Building Units. Tissue Eng. 16: 2051-2061, 2010. PMCID: PMC2949232.

Dean, D.M. and Morgan, J.R. Fibroblast Elongation and Dendritic Extensions in Constrained Versus Unconstrained Microtissues. Cell Motility and the Cytoskeleton 66: 129-141, 2009. PMID: 19170224.

Rago, A.P., Dean, D.M., Morgan, J.R. Controlling Cell Position in Complex Heterotypic 3D Microtissues by Tissue Fusion. Biotech. & Bioeng. 102: 1231-1241, 2009. PMID: 19012266.

Rago, A.P., Chai, P., Morgan, J.R. Encapsulated Arrays of Self-Assembled Micro-tissues: An Alternative to Spherical Microcapsules. Tissue Eng. 15: 387-395, 2009. PMID: 19193131.

Dean, D.M. and Morgan, J.R. Cytoskeletal-Mediated Tension Modulates the Directed Self-assembly of Microtissues. Tissue Eng. 14: 1989-1997, 2008. PMID: 18673088.

Barbone, D., Yang, T-M, Morgan, J.R., Gaudino, G., Broaddus, V.C. mTOR Contributes to the Acquired Multicellular Apoptotic Resistance of Human Malignant Mesothelioma Spheroids. J. Biol. Chem. 283: 13021-13030, 2008. PMCID: PMC2259263.

Dean, D.M., Napolitano, A.P., Youssef, J., Morgan, J.R. Rods, Tori and Honeycombs. The Directed Self-Assembly of Microtissues with Prescribed Microscale Geometries. FASEB J. 21: 4005-4012, 2007. PMID: 17627028.

Napolitano, A.P., Chai, P., Dean, D.M., Morgan, J.R. Dynamics of the Self-Assembly of Complex Cellular Aggregates on Micro-Molded Non-Adhesive Hydrogels. Tissue Eng. 13: 2087-2094, 2007. PMID: 17518713.

1977 Departmental Award for Outstanding Achievement in Biology, Syracuse University, Syracuse, NY

1978 National Research Service Award in Viral Oncology

1983-1986 Damon Runyon Walter Winchell Postdoctoral Fellowship

1986-1988 Cancer Research Institute Postdoctoral Fellowship

1996 La Roche-Posay International Foundation Prize

1996 European Association of Plastic Surgeons Honorary Lecture

2014 Editorial board member of TECHNOLOGY

2015 Fellow, National Academy of Inventors

2016 Fellow, Amercian Institute of Medical and Biological Engineering

1983-1988 Post Doctoral Fellow, Massachusetts Institute of Technology and Whitehead Institute for Biomedical Research

1988-1991 Co-founder, Somatix Corporation, Cambridge, MA

1988-1990 Senior Scientist, Somatix Corporation, Cambridge, MA

1990-1991 Scientific Officer, Somatix Corporation, Cambridge, MA

1991-1994 Instructor in Surgery, Harvard Medical School, Boston, MA

1991-1996 Assistant Biologist, Dept. of Surgery, Massachusetts General Hospital, Boston, MA

1991-2002 Senior Research Scientist, Shriners Hospital for Children, Boston, MA

1997-2002 Associate Biologist, Dept. of Surgery, Massachusetts General Hospital, Boston, MA

1994-2000 Assistant Professor in Surgery, Harvard Medical School, Boston, MA

2001-2002 Associate Professor in Surgery, Harvard Medical School, Boston, MA

2002-2004 Associate of Professor of Medical Science, Brown University, Providence, RI

2005-2013 Associate of Professor of Medical Science and Engineering, Brown University, Providence, RI

2013- Professor of Medical Science and Engineering, Brown University, Providence, RI

2021- Donna Weiss ’89 and Jason Weiss, Director of the Center for Alternatives to Animals in Testing, Brown University, Providence, RI

Course Director, Bio 213 Techniques in Molecular and Cellular Sciences, Brown University

Course Director, Bio 195/196 Independent Research, Brown University

Co-Director, Bio 223/224 Artificial Organs/Biomaterials/Tissue Engineering Seminar, Brown University

Lecturer, "Cell Adhesion" PH199/BI194 Biophysical Techniques, Brown University

Lecturer, "Drug Delivery in Dermatological Diseases" Bio 274 Organ System Pharmacology, Brown University Medical School

Lecturer, "Living Skin Equivalents" Bio 108 Organ Replacement, Brown University

Lecturer, "Cells and Cell Culture" Bio 114 Tissue Engineering, Brown University

Lecturer, "Viral-Mediated Gene Delivery" Bio 211 Drug and Gene Delivery, Brown University

Lecturer, "Introduction to Gene Therapy" Bio 17 Biotechnology in Medicine, Brown University

Lecturer, "Advances in Gene Therapy" Bio 217 Receptors, Channels and Signaling, Brown University

Course Director and Instructor, HST 505: Laboratory in Molecular and Cellular Sciences, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard-MIT Division of Health Science & Technology

Lecturer, "Burn Surgery and Tissue Engineering" HST 595, Tutorial in Medical Engineering and Medical Physics, Massachusetts Institute of Technology

Lecturer, "Industrial Round Table" HST 596 Tutorial in Medical Engineering and Medical Physics, Massachusetts Institute of Technology

Lecturer, "Improving Cultured Skin Performance by Stimulating the Innate Immune Response" Surgical Grand Rounds, Massachusetts General Hospital

Lecturer, "Composite Skin Experience" Surgical Grand Rounds, Massachusetts General Hospital

Lecturer, "Skin Biology and Engineering", Seminar Series in Biomedical Science and Engineering, Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA

Lecturer, "Gene Delivery to Keratinocytes" Genetics 208, Gene Therapy: Principles and Practice, Harvard Medical School

Lecturer, "Growth Factor Gene Therapy for Wound Healing of the Skin" Biomedical Colloquium Series, Graduate Programs in Biomedical Science, Bouve College of Pharmacy and Health Sciences, Northeastern University

Lecturer, "Genetic Control of Paracrine and Autocrine Controls of the Skin" Department of Pathology/Research North Seminar Series, Beth Israel Hospital

Lecturer, "Engineering Genetic Strategies For Tissue Repair" HST 590, Biomedical Engineering Seminars, Section on Molecular and Cellular Processes, Massachusetts Institute of Technology