Research in the lab is focused on understanding the molecular and cellular biology of the skin with an eye towards new therapeutic approaches to wound healing, the repair of the skin and the improvement in the performance of percutaneous medical devices. We are also working on novel devices containing living cells to profile gene expression, monitor the toxicity of nanomaterials, and to study the dynamics of the cell adhesion process.

Biography

B.S. Syracuse University
Ph.D. Harvard University
Post Doctoral Fellow Massachusetts Institute of Technology
and Whitehead Institute for Biomedical Research

Research Description

There are four interdisciplinary and collaborative projects in the lab.

1. In collaboration with Dean Clyde Briant (Eng) and funded by the Veterans Adminstration, we are investigating ways to improve the performance of percutaneous medical devices that penetrate the skin. There are over a million percutaneous devices (indwelling catheters, dialysis ports, etc.) implanted each year, and the long-term use of these devices is severely limited due to problems of inflammation and infection because the skin does not form an adequate seal around the device. This is especially problematic for a new titanium osseo-integration device that is being tested for the repair of amputations. The device is anchored in the bone and extends out through the skin where a prosthetic limb is attached. To optimize the skin seal around this device, we are investigating the influence of surface chemistry, surface topography and alloy composition on the adhesion and proliferation of epidermal keratinocytes and dermal fibroblasts. We are also investigating the mechanics of the skin/percutaneous device interface.


2. In collaboration with Profs. Robert Hurt (Eng), Agnes Kane (Pathobiology), and Gregory Crawford (Eng) and funded by an NSF Nanotechnology Interdisciplinary Research Team grant, we are developing a device to screen for potential toxic effects of nano-materials on target organs such as the lung and skin. Nanotechnology holds great promise for advancements in many fields including medicine, electronics and materials science. However, the health effects of these new materials is largely unknown, and humans may come into contact with nano-materials through deliberate or accidental inhalation or contact with the skin. To investigate potential toxic effects, we are developing a high throughput chip containing microarrays of nanomaterials (single wall/multiwall carbon nanotubes, nanohorns, gold nanoparticles and gold/titanium nanoparticles). The biochemical responses of skin cells and macrophages grown on these chips are being measured to determine the cellular responses to these new materials with the goal of determining those nanoscale features that lead to minimal toxicity and optimal biocompatibility.


3. In collaboration with Drs. Martin Yarmush and Mehmet Toner (Harvard Medical School) and funded by an NIH Bioengineering Research Partnership grant, we are developing a living cell array containing genetically modified cells that have been engineered to induce the expression of green fluorescent protein in response to a large panel of well-known inflammatory mediators. Unlike the profiling of gene expression using conventional genomics tools that require the killing of cells and the extraction of RNA, the living cell array reports the kinetics and duration of gene expression in real-time by quantifying the fluorescence of living cells. This data has generated new insight into the signal transduction of inflammatory mediators. As the panel of reporter genes and reporter cell lines is expanded to develop a massively parallel high throughput system for the simultaneous monitoring of the expression of hundreds of genes, the device will generate new algorithms for understanding how a cell perceives and integrates the conflicting signals from a complex and sometimes pathological milieu.


4. As part of Brown's NSF sponsored Materials Research Science and Engineering Center on Micro- and Nano-Mechanics of Materials, we are investigating the fundamental processes of cell to cell and cell to material adhesion. We have developed a novel and highly effective method to form aggregates of cells. A hydrogel such as agarose that is non-adhesive for cells is micro-molded to have small wells. A suspension of single cells is added and the cells settle into these wells and instead of binding to the surface of the hydrogel, the cells contact one another and form small tight aggregates of cells. This is almost the exact opposite of the conventional culture of cells on Petri dishes where the cells bind and spread on the plastic surface of the dish. Using this method we are examining the dynamics of cell to cell adhesion as well as the fundamental processes governing the self assembly of cells into functional micro-tissues.

Awards

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

Affiliations

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

Funded Research

Veterans Administration
"Optimizing the Soft Tissue Seal Around a Percutaneous Osseointegration Device"

National Institute of Health
Bioengineering Research Partnership (BRP): "Inflammatory Signal Transduction in Living Cell Arrays"

National Science Foundation
Nanotechnology Interdisciplinary Research Team (NIRT): "Micropatterned Nanotopography Chips for Probing the Cellular Basis of Biocompatibility and Toxicity"

National Science Foundation
Materials Research Science and Engineering Center: "Micro- and Nano- Mechanics of Materials: Micromechanics of Cell Adhesion"

Teaching Experience

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

Courses Taught

• Artificial Organs/Biomaterials/Tissue Engineering Seminar (BI0223)
• Artificial Organs/Biomaterials/Tissue Engineering Seminar (BI0224)
• Laboratory in Molecular and Cellular Sciences (HST505)
• Techniques in Molecular and Cell Science (BI0213)

View My Full Publication List in pdf format

Selected Publications

• Xu, C., Xie, J., Ho, D., Wang, C., Kohler, N., Walsh, E.G., Morgan, J.R., Chin, Y.E., Sun, S. Au-Fe3O4 Dumbbell Nanoparticles as Dual Functional Probes. Angew. Chem. Int. Ed., 47, 173-176, 2008.(2008)
• Rago, A.P., Napolitano, A.P., Morgan, J.R. Miniaturization of an Anoikis Assay Using Non-Adhesive Micromolded Hydrogels. Cytotechnology, 56: 81-90, 2008.(2008)
• 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(2008)
• Dean, D. M. and Morgan, J.R. Cytoskeletal-Mediated Tension Modulates the Directed Self-assembly of Microtissues. Tissue Eng. 14, 1989-1997, 2008. Faculty of 1000 Biology: evaluations for Dean DM & Morgan JR Tissue Eng Part A 2008 Dec 14 (12) :1989-97 http://www.f1000biology.com/article/id/1132868/evaluation(2008)
• Holt, B., Tripathi, A. and Morgan, J.R. Viscoelastic Response of Human Skin to Low Magnitude Physiologically Relevant Shear. J. Biomechanics, 41, 2689-2695, 2008.(2008)
• 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 Engineering, 13(8): 2087-2094. 2007.(2007)
• Jarrell, J. D., .Eun, T. H., Samale, M, Briant, C., Sheldon, B., Morgan, J.R. Metal Oxide Coated (MOC) Cell Culture Arrays for Rapid Biological Screening. Journal of Biomedical Materials Research: Part A. 83A: 853-860, 2007.(2007)
• 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.(2007)
• Napolitano, A.P., Dean, D.M., Man, A.J., Youssef, J., Ho D.N., Rago, A.P, Lech, M.P., Morgan, J.R. Scaffold-free 3-Dimensional Cell Culture Utilizing Micro-Molded Non-Adhesive Hydrogels. BioTechniques, 43: 494-500, 2007.(2007)
• Campaner, A.B., Ferreira, L.M., Gragnani, A., Bruder, J.M., Cusick, J., Morgan, J.R. Upregulation of TGF-1 Expression May Be Necessary, But Is Not Sufficient For Excessive Scar Formation. J Invest Dermatol. 2006, 126: 1168-1176(2006)
• Paek, H.J., Campaner, A.B., Kim, J.L., Golden, L., Aaron, R.K., Ciombor, D.M., Morgan, J.R., Lysaght, M.J. Microencapsulated Cells Genetically Modified to Overexpress hTGF-1: Viability and Functionality in Allogeneic and Xenogeneic Implant Models. Tissue Engineering. 2006 12: 1733-1739.(2006)
• Dabiri, G., Campaner, A.B., Morgan, J.R., Van De Water, L. TGF-1 Regulates Focal Adhesion Structure in Hypertrophic Scar Myofibroblasts Through An Autocrine Loop. J Invest Dermatol. 2006, 126: 963-970.(2006)
• Paek, H.J., Moise, L., Morgan, J.R., Lysaght, M.J. Origin of Insulin Secreted from Islet-Like Cell Clusters Derived from Murine Embryonic Stem Cells. Cloning and Stem Cells. 2005: 7: 226-231.(2005)
• Paek, H.J., Campaner, A.B., Kim, J.L., Aaron, R.K., Ciombor, D.M., Morgan, J.R., Lysaght, M.J. In Vitro Characterization of TGF-1 Released From Genetically Modified Fibroblasts in Ca2+ -Alginate Microcapsules. ASAIO J. 2005, 51: 379-384.(2005)
• Paek, H.J., Morgan, J.R., Lysaght, M.J. Sequestration and Synthesis: The Source of Insulin in Cell Clusters Differentiated From Murine Embryonic Stem Cells. Stem Cells. 2005; 23: 862-867.(2005)
• Erdag, G. and Morgan, J.R. Allogeneic versus Xenogeneic Immune Reaction to Bioengineered Skin. Cell Transplantation, 2004; 13, 701-712.(2004)
• Erdag, G., Medalie, D.A., Rakhorst, H., Krueger, G.G., and Morgan, J.R. FGF-7 Expression Enhances the Performance of Bioengineered Skin. Molecular Therapy, 2004; 10, 76-85.(2004)
• Davis, H. E., Rosinski, M., Morgan, J.R., Yarmush, M.L. Charged Polymers Modulate Retrovirus Transduction Via Membrane Charge Neutralization and Virus Aggregation. BioPhysical Journal. 2004; 86, 1234-1242..(2004)
• Hamoen, K.E., and Morgan, J.R. Transient Hyperproliferation of a Transgenic Human Epidermis Expressing Hepatocyte Growth Factor. Cell Transplantation, 2002; 11:385-395.(2002)
• Davis, H. E., Morgan, J.R., Yarmush, M.L. Polybrene Increases Retrovirus Gene Transfer Efficiency by Enhancing Receptor-Independent Virus Adsorption on Target Cell Membranes. BioPhysical Chemistry. 2002, 97:159-172.(2002)
• Erdag, G. and Morgan, J.R. IL-1 and IL-6 Enhance the Anti-Bacterial Properties of Cultured Composite Keratinocyte Grafts. Annals of Surgery, 2002; 235: 113-124.(2002)
• Gragnani, A., Morgan, J.R., Ferreira, L.M. Differentiation and Barrier Formation in a Cultured Composite Skin Graft. J. Burn Care & Rehab., 2002; 23: 126-131.(2002)
• Machens H-G., Morgan, J.R., Berthiaume, F., Stefanovich, P., Siemers, F., Krapohl, B., Berger A., Mailänder, P. PDFG-AA Mediated Functional Angiogenesis in the Rat Epigastric Island Flap After Genetic Modification of Fibroblasts is Ischemia Dependent. Surgery, 2002, 131:393-400.(2002)
• Erdag, G. and Morgan, J.R. Survival of Fetal Skin Grafts is Prolonged on the Human Peripheral Blood Lymphocyte Reconstituted-Severe Combined Immunodeficient Mouse/Skin Allograft Model. Transplantation, 2002; 73: 519-528.(2002)
• Erdag, G., Eroglu, A., Morgan, J.R., Toner, M. Cryopreservation of Fetal Skin Is Improved By Extracellular Trehalose. Cryobiology. 2002; 44: 218-228.(2002)
• Jarrell, J. D., Dolly, B., Morgan, J.R. Controlled Release of Vanadium from Titanium Oxide Coatings for Improved Integration of Soft Tissue Implants. Journal of Biomedical Materials Research: Part A. In Press.
• Rago, A.P., Chai, P., Morgan, J.R. Encapsulated Arrays of Self-Assembled Micro-tissues: An Alternative to Spherical Microcapsules. Tissue Eng. In Press.
• Patel, R., Jeanbart, L., Temu, T., Morgan, J.R. Lysaght, M.J. A Localizable, Biological-based System for the Delivery of Bioactive IGF-1 Utilizing Microencapsulated Genetically Modified Human Fibroblasts. ASAIO J. In Press.
• Rago, A.P., Dean, D. M., Morgan, J.R. Controlling Cell Position in Complex Heterotypic 3D Microtissues By Tissue Fusion. Biotech. and Bioeng. In Press
• Dean, D. M. and Morgan, J.R. Fibroblast Elongation and Dendritic Extensions in Constrained Versus Unconstrained Microtissues. Cell Motility and the Cytoskeleton, In Press.