About

Jeffrey Morgan is a Professor of Medical Science and a Professor of Engineering at Brown University. His research interests include health, life sciences, and biotechnology, with recent activities highlighted by his involvement in innovations and startups that focus on breakthrough technologies in these fields. He has contributed to the development of new models for investigating fibrosis treatments without the use of animals, notably a sophisticated 3D connective tissue model that aids in understanding connective tissue disorders and testing potential treatments. His work is recognized within the Brown community and the broader scientific and entrepreneurial ecosystem, exemplified by his participation in events such as the Innovation at Brown Showcase and Rhode Island Startup Week.

Research topics

• Biology
• Chemistry
• Cell biology
• Medicine
• Biophysics

Selected publications

• TNF-α and IL-1β but not IL-18 counteract TGF-β1 mediated stimulation of collagen accumulation and increased extracellular matrix strength and stiffness

  Scientific Reports · 2026-05-02

  articleOpen accessSenior author

  Cytokine-mediated cross-talk between immune cells and fibroblasts is a driver of excessive ECM accumulation during fibrosis. In this study, we used a 3D in vitro model of a connective tissue to discern the roles of three pro-inflammatory cytokines; TNF-α, IL-18 and IL-1β, alone, and in combination with TGF-β1 to simulate the fibrotic environment. Ring-shaped tissues were formed by seeding human fibroblasts into circular molds of agarose, wherein the cells self-assembled, formed a 3D tissue and synthesized de novo a collagen-rich ECM. Cytokine treated tissues were analyzed at days 7 and 14 by histology and measured for thickness, collagen, DNA and strength and stiffness by tensile testing. Despite their pro-inflammatory nature, none of the cytokines increased collagen alone or in combination with TGF-β1. TNF-α and IL-1β reduced collagen, tissue strength and stiffness, and altered tissue morphology. When combined with TGF-β1, TNF-α and IL-1β counteracted TGF-β1-mediated increases in collagen, strength, and stiffness. In contrast, IL-18 had minimal effects alone or when combined with TGF-β1. These data suggest that IL-18 has no effect on fibroblast activation, whereas TNF-α and IL-1β may modulate TGF-β1's effects. This 3D model of a human collagen-rich tissue can help define cytokine-mediated cross-talk between immune cells and fibroblasts.

  PublisherDOI

• Multi-assay assessment of cytotoxicity reveals multiple mechanisms of action in 3D microtissues

  Scientific Reports · 2025-01-24 · 8 citations

  articleOpen access

  Cell viability assays are an integral component of toxicology and high-throughput drug screening studies; however, many assays rely on a single biomarker of cell death which provides an incomplete assessment of cell viability. Here, we introduce an innovative approach that combines data from multiple assays using a linear mixed effects regression model and principal component analysis. We explored the cytotoxic response of various assay-treatment combinations using four assays with distinct mechanisms of action and seven different treatments across three types of microtissue cultures. The multi-assay data revealed the presence of multifaceted cellular injuries which highlight the need for multimodal approaches to better understand complex disruptions to viability. By incorporating outputs from the four assays, we introduced a new lethal concentration threshold that captures changes from different cellular injuries to provide a more comprehensive evaluation of cytotoxicity. Overall, the proposed approach provides a unique opportunity to analyze data from multiple assays in a holistic manner to improve the predictive power of drug screening and toxicology studies.

  PublisherOA PDFDOI

• TGF-β1 requires IL-13 to sustain collagen accumulation and increasing tissue strength and stiffness

  Connective Tissue Research · 2025-02-27 · 3 citations

  articleSenior authorCorresponding

  AIMS: Fibrosis is a multifactorial process characterized by the excessive accumulation of extracellular matrix (ECM), increased tissue stiffness, and decreased elasticity. This study examined how individual cytokines and a cytokine combination alter collagen production and biomechanics in a 3D in vitro model of the human ECM. METHODS: Cultured human fibroblasts were seeded into a circular agarose trough molded in 24 well plates. The fibroblasts aggregated and formed a 3D ring-shaped tissue that synthesized de novo a collagen-rich human ECM complete with collagen fibrils. Unlike existing models, no macromolecular crowders were added, nor artificial scaffolds or exogenous ECM proteins. Rings were treated with TGF-β1, IL-13 or the combination of TGF-β1 and IL-13 for up to 3 weeks. Morphology, histology, collagen, DNA, fibril formation, gene expression and tensile properties of the rings were measured. RESULTS: As the rings compacted, cellularity and total DNA decreased, whereas total collagen accumulated. TGF-β1 stimulated collagen accumulation and increased ring biomechanics at day 7, but these increases stalled and declined by day 21. When treated with IL-13, a cytokine exclusive to the immune system, there were no significant differences from control. However, when TGF-β1 was combined with IL-13, collagen levels and ring biomechanics increased over the entire three weeks to levels higher than TGF-β1 alone. Gene expression was differentially regulated by cytokine treatment over the entire three weeks suggesting that increased collagen accumulation was not due to upregulation of collagen gene expression. CONCLUSIONS: These results suggest that TGF-β1 requires a second signal, such as IL-13, to sustain the long-term pathological increases in collagen accumulation and biomechanics that can compromise the function of fibrotic tissues.

  PublisherDOI

• Paper 55: Differences in Symmetry Of Jump Landing Biomechanics Between Hamstring and Quadriceps Tendon Autografts for Anterior Cruciate Ligament Reconstruction

  Orthopaedic Journal of Sports Medicine · 2025-09-01

  articleOpen access

  Objectives: Anterior cruciate ligament reconstruction (ACLR) in adolescent patients is commonly performed utilizing hamstring (HT) or quadriceps (QT) tendon autografts. However, differences in jump landing biomechanics between these two graft types remains unclear. Understanding these differences can inform a graft-specific rehabilitation approach to improve jump landing biomechanics. The purpose of this study was to compare symmetry of jump landing biomechanics during drop vertical jump among ACLR patients with HT and QT grafts. Methods: This retrospective study included 53 adolescents who underwent unilateral ACLR (HT=23 patients; 12 female/11 male, QT=30 patients ; 16 female/14 male, mean age 16.1±1.3). Motion analysis data were collected during drop vertical jump between 7 to 9 months post-surgery. Drop vertical jump was captured using a 20 camera optical motion capture system (Vicon Motion Systems, Oxford, UK) synchronized with two Bertec force plates (Bertec Corporation, Columbus, OH). Anthropometrics, jump height, and ground reaction time were recorded. Variables of interest included maximum hip and knee flexion angles and maximum knee and hip flexion moments were calculated using the Dynamic Plug-in Gait Model. Energy absorption (average negative power) during landing and energy generation (average positive power) at maximal height vertical jumping were calculated by summing the joint work in all three planes and then divided by the time from initial contact to take off. The percentage of hip and knee power was derived as a ratio of the average power at the individual joint divided by the sum of the average power within the limb at the hip, knee, and ankle. Inter-limb asymmetry of each motion analysis variable was calculated as Bilateral Asymmetry Index (AI) between each limb (surgical versus non-surgical). A majority of participants completed the Pediatric International Knee Documentation Committee (Ped-IKDC) Subjective Knee Evaluation Form at the drop vertical measurement. Participants were grouped by graft type into HT (hamstring tendon) group and QT (quadricpes tendon) group, and participant characteristics were compared between two groups. Anthropometric information, jump height and ground reaction time were compared between HT and QT group by using unpaired t test. Motion analysis variables of surgical limb in HT group versus QT group, and non-surgical limb in HT group versus QT group were compared by using Mann-Whitney test. Differences in AI of biomechanical variables and Ped-IKDC score were also compared between two groups using Mann-Whitney test. Results: There were no differences in anthropometrics, jump height, ground contact time between two groups. Compared to HT group, QT group demonstrated 1) smaller maximum knee angles in surgical limb, 2) lower hip flexion moments in operated and non-operated limbs, 3) lower knee flexion moments in operated limbs, 4) lower negative power percentage and lower positive power percentage at the knee in operated limbs, and 5) higher positive power percentage at the hip in operated limbs (p<0.05). Asymmetries relative to the non-surgical limb observed in QT groups were greater compared to that in HT groups for 1) maximum knee and hip flexion angles, 2) knee flexion moments, 3) negative power percentage and positive power percentage at the knee. Conversely, asymmetries were smaller in the QT groups for negative power percentage and positive power percentage at the hip (p<0.05). There were no differences in Ped-IKDC score between two groups. Conclusions: Adolescent patients who underwent ACLR using QT graft demonstrated greater offloading at the knee and compensated with the hip in the surgical limb during jump landings, compared to those with HT grafts. Graft choice of QT or HT graft in ACLR may influence the knee biomechanical asymmetries. Further studies are required to determine how long these asymmetries persist. A graft-specific approach during rehabilitation may be needed to provide optimal return to sport and reinjury rate success between graft types.

  PublisherDOI

• Fluid-Inspired Fiber Analysis of 3D Collagen Architecture

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Environment

  2025-01-01

  other1st authorCorresponding
  PublisherDOI

• An in vitro model to measure the strength and stiffness of the extracellular matrix synthesized de novo by human fibroblasts

  In vitro models · 2025-03-07 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Establishing scientific confidence in a two-chamber co-culture system to evaluate androgenic response in the presence of hepatic metabolism

  Toxicology Letters · 2025-09-01

  articleOpen access

  For the in vitro determination of toxicity on target organs in the presence of physiologically relevant human metabolism, we recently developed a two-chamber liver-target organ co-culture system in a medium-throughput 96-well format. Our proof-of-concept study using human HepaRG microtissues cultured in three-dimension (3D) and AR-CALUX reporter cells demonstrated the significantly reduced testosterone (T)-mediated androgen receptor (AR) responses in the presence of human liver metabolism. The present study further increased the scientific confidence in this two-chamber co-culture system as a flexible and robust tool to capture androgen-mediated responses by incorporating alternate AR reporter cell systems as the target and examining additional androgenic compounds. The system generated concordant metabolism-dependent changes in T- and 5α-dihydrotestosterone (DHT)-mediated AR responses using two different AR reporter cell systems (AR-CALUX, AR-INDIGO). The AR reporters had different sensitivity ranges and required media optimization. We demonstrated that this two-chamber co-culture system with integrated hepatic biotransformation can be used to evaluate endocrine activity with potential metabolism modulation of parent compounds.

  PublisherDOI

• Development of a human liver microphysiological coculture system for higher throughput chemical safety assessment

  Toxicological Sciences · 2024-02-09 · 6 citations

  articleOpen access

  Chemicals in the systemic circulation can undergo hepatic xenobiotic metabolism, generate metabolites, and exhibit altered toxicity compared with their parent compounds. This article describes a 2-chamber liver-organ coculture model in a higher-throughput 96-well format for the determination of toxicity on target tissues in the presence of physiologically relevant human liver metabolism. This 2-chamber system is a hydrogel formed within each well consisting of a central well (target tissue) and an outer ring-shaped trough (human liver tissue). The target tissue chamber can be configured to accommodate a three-dimensional (3D) spheroid-shaped microtissue, or a 2-dimensional (2D) cell monolayer. Culture medium and compounds freely diffuse between the 2 chambers. Human-differentiated HepaRG liver cells are used to form the 3D human liver microtissues, which displayed robust protein expression of liver biomarkers (albumin, asialoglycoprotein receptor, Phase I cytochrome P450 [CYP3A4] enzyme, multidrug resistance-associated protein 2 transporter, and glycogen), and exhibited Phase I/II enzyme activities over the course of 17 days. Histological and ultrastructural analyses confirmed that the HepaRG microtissues presented a differentiated hepatocyte phenotype, including abundant mitochondria, endoplasmic reticulum, and bile canaliculi. Liver microtissue zonation characteristics could be easily modulated by maturation in different media supplements. Furthermore, our proof-of-concept study demonstrated the efficacy of this coculture model in evaluating testosterone-mediated androgen receptor responses in the presence of human liver metabolism. This liver-organ coculture system provides a practical, higher-throughput testing platform for metabolism-dependent bioactivity assessment of drugs/chemicals to better recapitulate the biological effects and potential toxicity of human exposures.

  PublisherOA PDFDOI

• OCT Viability Imaging of 3D Microtissues

  2024-01-01

  article

  Functional precision medicine directly screens chemotherapeutics in patient tissue; however, technical challenges limit its clinical feasibility. OCT viability imaging in 3D microtissues overcomes these limitations and has shown tissue and treatment specific changes in viability.

  PublisherDOI

Recent grants

• NIH Grant R29AR042012

  NIH · $502k · 1998

• PFI-TT: Automated Manufacturing of Blood Vessels

  NSF · $200k · 2018–2020

• NIH Grant R01EB008664

  NIH · $661k · 2012

• Collaborative Research: Integrative Modeling and Analysis of Animal-Cell Cytokinesis

  NSF · $600k · 2007–2012

• NIH Grant P01HD028528

  NIH · $9.5M · 2004

Frequent coauthors

• Martin L. Yarmush

  Shriners Hospitals for Children - Boston

  157 shared

• Joseph M. Le Doux

  The Wallace H. Coulter Department of Biomedical Engineering

  65 shared

• Karen E. Hamoen

  Erasmus MC

  55 shared

• Howard E. Davis

  Shriners Hospitals for Children - Erie

  43 shared

• Benjamin T. Wilks

  Shriners Hospitals for Children - Boston

  36 shared

• Mehmet Toner

  Harvard University

  33 shared

• Anubhav Tripathi

  Providence College

  32 shared

• Charles M. Roth

  Rutgers, The State University of New Jersey

  30 shared

Education

• B.S., Biology

  Syracuse University

  1977