About

Linda G. Griffith, PhD, is a Professor of Teaching Innovation at the MIT Department of Biological Engineering. Her research encompasses molecular-to-systems level analysis, design, and synthesis of biomaterials, scaffolds, devices, and micro-organs for applications in regenerative medicine, tissue engineering, and in vitro drug development. A central theme of her work is connecting experimental systems to systems biology measurements. Her projects are highly interdisciplinary and translational, involving basic scientists, clinicians, and engineers, often with industry partners, to solve important problems in medicine and biology. Prof. Griffith received a Bachelor's Degree from Georgia Tech and a PhD degree from the University of California at Berkeley, both in chemical engineering. She is a member of the National Academy of Engineering and has received numerous awards, including a MacArthur Foundation Fellowship, the Popular Science Brilliant 10 Award, NSF Presidential Young Investigator Award, the MIT Class of 1960 Teaching Innovation Award, and Radcliffe Fellowships. Her research and contributions focus on the design and synthesis of biomaterials that control receptor-mediated processes in highly targeted and biophysically-appropriate ways, advancing the fields of regenerative medicine, tissue engineering, and drug development.

Research topics

• Biology
• Chemistry
• Cell biology
• Microbiology
• Internal medicine
• Immunology
• Medicine
• Biochemistry
• Obstetrics
• Cancer research
• Genetics
• Endocrinology
• Bioinformatics
• Physiology
• Physics
• Gynecology
• Environmental health
• Optics

Selected publications

• A vascularized liver microphysiological system captures key features of hepatic insulin resistance and monocyte infiltration

  Nature Communications · 2026-02-03 · 2 citations

  articleOpen accessSenior author

  In vitro models can recapitulate aspects of human liver diseases, thereby aiding therapeutic development. Dynamic interactions with vascular and immune cells contribute to disease progression in ways that are challenging to capture in the hepatic spheroid models commonly used for assessing facets of metabolism and disease. To address this, we developed a microphysiological system (MPS) featuring multicellular human hepatic spheroids physically integrated with self-organized microvascular networks. We demonstrate this MPS's utility by modeling an insulin resistance state, where chronic exposure to disease-mimetic conditions yields altered hepatocyte metabolism, dysregulated vascular features, and increased inflammation state. We extend this system to capture disease-relevant changes in immune cell recruitment, showing that monocytes perfused through the vasculature will extravasate toward hepatic spheroids, with insulin-resistant samples exhibiting greater infiltration. Altogether, this vascularized liver MPS captures local hepatocyte-immune-microvascular interactions in an accessible microfluidic platform, enabling the study of clinically relevant immune-tissue interactions in complex metabolic disease.

  PublisherOA PDFDOI

• WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Pain): methods to assess pain behaviour in rodent models of endometriosis

  Molecular Human Reproduction · 2025-01-01 · 8 citations

  reviewOpen access

  Pain is a debilitating symptom of endometriosis, and its mechanisms are often explored using rodent models. However, a lack of harmonization amongst models and behavioural measures, in addition to inconsistent reporting, might limit the overall clinical relevance and hinder translation of findings. An additional challenge is accurately linking rodent behaviour to human experiences of endometriosis. This study aimed to: (i) review current measures of pain-associated behaviours used in endometriosis studies; (ii) recommend best practices for each method and their suitability to study endometriosis-associated pain; and (iii) develop internationally agreed-upon standard operating procedures ('EPHect-EM-Pain SOPs'). The World Endometriosis Research Foundation (WERF) assembled an international working group, from which a 'pain behaviour working group' consisting of experts in the field was established. The group used additional consultation from experimental pain model scientists in the broader field. Stimulus-evoked (reflexive) and stimulus-independent (spontaneous) measures are currently used to assess pain-associated behaviours in rodents with experimental endometriosis. All existing methods offer advantages and limitations regarding ethological relevance, output quality, and equipment/training requisites. Internationally standardized pain SOPs as well as summary documentation outlining the minimum and standard requirements for several behavioural measures were developed, as well as consensus recommendations on experimental designs and documentation. To more closely reflect the lived experiences of those with endometriosis, the consortium recommends that, following validation, multiple types of pain-related and/or parallel rodent behaviours (e.g. anxiety) should be quantified as surrogate outcome measures for endometriosis-associated pain. These harmonized methods and documentation for endometriosis research will facilitate essential comparisons among studies, improve translational applicability, and provide a superior holistic view of animal (and thus human) wellbeing.

  PublisherDOI

• WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Heterologous): heterologous rodent models

  Molecular Human Reproduction · 2025-01-01 · 6 citations

  articleOpen access

  Endometriosis, defined as the growth of endometrial-like tissues outside the uterus, is a common disease among women. Numerous in vivo rodent models of endometriosis have been developed to explore multiple aspects of this poorly understood disease. Heterologous models utilize human endometrial tissues engrafted into immunocompromized mice, while homologous models engraft rodent endometrium into immunocompetent mice or rats. Heterologous models of endometriosis more closely replicate the human disease; however, the murine humoral immune response must be suppressed to prevent rejection of the xenograft tissue. Although the innate immune system remains intact, suppression of the humoral response leads to a markedly different local and systemic immune environments compared to humans. Despite this limitation, experiments using heterologous models have contributed significantly to our understanding of endometriosis establishment and progression, the pre-clinical effectiveness of various therapeutic strategies, and genetically modifiable host factors that contribute to disease. Unfortunately, a lack of harmonization of the models used by different laboratories has impeded the reproducibility and comparability of results between groups. Therefore, the World Endometriosis Research Foundation (WERF) formed an international working group of experts in heterologous models of endometriosis to develop guidelines and protocols that could contribute to unifying experimental approaches across laboratories. Nine critical variables were identified: (i) mouse strain; (ii) human tissue type; (iii) hormonal status of the human tissue donor; (iv) human tissue preparation; (v) method and location of tissue placement; (vi) hormonal status of the recipient animal; (vii) whether or not mice were engrafted with human immune cells; (viii) endpoint assessments; and (ix) number and type of replicates. Herein, we outline important considerations for each major variable and make recommendations for unification of approaches. Widespread adoption of harmonized protocols and implementation of standardized documentation and reporting should further improve the reproducibility and translation of experimental findings both within and between laboratories.

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• System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring

  Nature Communications · 2025-01-16 · 9 citations

  articleOpen access

  Three-dimensional subcellular imaging is essential for biomedical research, but the diffraction limit of optical microscopy compromises axial resolution, hindering accurate three-dimensional structural analysis. This challenge is particularly pronounced in label-free imaging of thick, heterogeneous tissues, where assumptions about data distribution (e.g. sparsity, label-specific distribution, and lateral-axial similarity) and system priors (e.g. independent and identically distributed noise and linear shift-invariant point-spread functions are often invalid. Here, we introduce SSAI-3D, a weakly physics-informed, domain-shift-resistant framework for robust isotropic three-dimensional imaging. SSAI-3D enables robust axial deblurring by generating a diverse, noise-resilient, sample-informed training dataset and sparsely fine-tuning a large pre-trained blind deblurring network. SSAI-3D is applied to label-free nonlinear imaging of living organoids, freshly excised human endometrium tissue, and mouse whisker pads, and further validated in publicly available ground-truth-paired experimental datasets of three-dimensional heterogeneous biological tissues with unknown blurring and noise across different microscopy systems. Three-dimensional imaging is crucial for biomedical research, yet microscopy faces axial resolution limitations. Here, authors introduce SSAI-3D that adapts training datasets and sparsely finetunes a network to achieve robust results across various biological samples and microscopy systems.

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• Lyme disease increases risk for multiple gynecological conditions

  medRxiv · 2025-03-06 · 1 citations

  preprintOpen access

  Abstract Lyme disease (LD) is an illness caused by the spirochete Borrelia burgdorferi ( B. burgdorferi ). Borrelia is known to disseminate through organs, including the skin, joints, spinal cord, bladder, and heart, leading to Lyme arthritis, neuroborreliosis, and Lyme carditis. While previous studies have investigated the impact of LD on pregnancy in both mice and humans and have found the presence of B. burgdorferi in the uterus of mice, we studied the impact of LD on the non-pregnant female reproductive tract. We use a mouse model for LD and find an ongoing and severe infection of the reproductive tract of female mice, which persists up to 15-months post-inoculation. This infection results in uterine glandular cysts and endometrial hyperplasia as well as vaginal epithelial thickening, polymorphonuclear and mononuclear cell epithelial infiltration, and epithelial desquamation into the vaginal lumen. Strikingly, we find that age has an impact on the extent of gynecologic pathology such that aged female mice (1-year old) that are reproductively senescent have more gynecologic pathology with infection compared to young mice (15-weeks old) when infected for the same length of time. Using large-scale electronic healthcare record data, we report that LD additionally results in increased infection-associated risk of menorrhagia (1.5-fold), miscarriage (1.62-fold), uterine fibroids (1.42-fold), and endometriosis (1.93-fold). Underreporting of gynecological outcomes is pervasive throughout many different infectious diseases, and LD-associated gynecological pathologies may have been similarly underappreciated in the field. This work suggests that further study of the female reproductive tract and the effects of B. burgdorferi infection therein will help clarify and expand the knowledge of myriad LD outcomes. Graphical abstract

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• Development of a Synthetic Hydrogel to Foster Microvascularization of an Endometriosis Microphysiological System

  Advanced Healthcare Materials · 2025-10-06

  preprintOpen accessSenior authorCorresponding

  The ascent of novel alternative methods in drug development spotlights the dual needs for improved biological fidelity to in vivo, along with reproducibility, especially in regulatory applications. The need for pre-clinical models of patient-derived endometriosis lesions motivates the development of a vascularizable, completely synthetic extracellular matrix (v-CS-ECM) that supports morphogenesis of perfusable microvasculature in a microfluidic device, in the context of relevant lesion cells. This paper describes v-CS-ECM, a peptide-modified polyethylene glycol-based hydrogel crosslinked with a cell-degradable peptide that achieves these dual goals. Vessels form by morphogenesis after the liquid v-CS-ECM precursor, containing endothelial cells and fibroblasts, is injected into the tissue compartment to encapsulate cells. Vessel formation is influenced by ECM biochemical and biophysical properties, the source of vascular cells, and microphysiological system operating conditions. The v-CS-ECM also supports the co-culture of endometrial epithelial organoids and fibroblasts, and formation of microvascularized endometriosis lesion-like structures when all cell types are co-encapsulated in a microfluidic device with constant flow. Hence, v-CS-ECM has the potential to improve preclinical evaluation of endometriosis drug efficacy by enabling microvascularized patient-derived lesion models.

  PublisherDOI

• WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Organoids): endometrial organoids as an emerging technology for endometriosis research

  Molecular Human Reproduction · 2025-01-01 · 12 citations

  reviewOpen access

  The aetiology of endometriosis remains poorly understood. In vitro model systems provide the opportunity to identify the mechanisms driving disease pathogenesis using human cells. Three-dimensional models, particularly organoid systems, have revolutionized how we study epithelial biology and are powerful tools for modelling endometriosis. As an emerging model system, it is important to define protocols and identify the remaining challenges surrounding endometrial organoid culture to increase reproducibility and scientific rigour in endometriosis research. The World Endometriosis Research Foundation (WERF) established an international working group comprised of experts using in vitro approaches for the study of endometriosis. This working group harmonized protocols and documentation of existing and emerging organoid systems to maximize comparison and replication across the field and guide specific research hypotheses testing. This evaluation of organoid protocols, limitations, challenges, and alternative approaches assessed both published and grey literature papers across several disciplines pertinent to endometriosis research. Recommendations for protocol and documentation harmonization are presented, and we created the first-ever decision tree diagram to guide and facilitate the selection of existing models best suited for specific areas of endometriosis research. Rigorous and systematic assessment of emerging organoid systems, recognizing the inferential strengths and limitations of these approaches, is vital for endometriosis research. This comprehensive review of the benefits, limitations, and utilization of organoid models, as well as the consequent integration of protocols and documentation, will contribute to the scientific knowledge base by maximizing the reproducibility, comparability, and interpretation of research studies in endometriosis. Additionally, these newly developed protocols and documentation should serve as a resource for, and facilitate collaboration between, endometriosis investigators using organoids in their research methods.

  PublisherDOI

• Simultaneous Label-free Imaging of Nucleolar Dynamics and Subcellular Metabolic Shifts Across Tissue Contexts

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-08

  preprintOpen access

  The nucleolus is essential for ribosome biogenesis and for regulating cellular responses to growth and stress, and its relationship to cellular metabolic activity and functional state highlights its potential as a biomarker of cellular health. However, challenges in contrast multiplexing and high-resolution isotropic three-dimensional (3D) imaging hinder the non-invasive, simultaneous assessment of nucleolar activity and subcellular metabolic maps across different tissue contexts, especially in complex 3D environments. To fully harness the nucleolus's potential as a biomarker and diagnostic target, we present a multimodal imaging platform that combines third harmonic generation (THG) imaging with metabolic autofluorescence of NAD(P)H and FAD to study structural and metabolic nucleolar dynamics. Enabled by a high-power multimode fiber source and an axial deblurring network, we achieved ∼ 400 nm isotropic resolution in deep 3D imaging and confirmed the high accuracy of our method for label-free nucleolus identification using co-registered immunostaining and electron microscopy. To establish the biological relevance of our approach, we demonstrate that nucleolar stress leads to an unexpected depletion of NADH across cellular compartments. Furthermore, in the human endometrium-where nucleolar dynamics are central to the tissue's response to progesterone-our label-free imaging strategy delineated endometrial structures in freshly excised tissues and revealed that progesterone treatment induces distinct changes in nucleolar translocation and metabolic adaptation in organoids derived from diseased patients compared to controls. This capacity to non-invasively visualize and quantify features of the nucleolus and its local metabolic microenvironment at single-cell resolution in human tissues-and dynamically track these changes over time in patient-derived organoids-provides a powerful tool for uncovering the roles of the nucleolus in development, disease progression, and therapeutic response. Together, these findings establish our platform as a significant advance for both fundamental research and organelle-based tissue diagnostics.

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• Computational modeling of hormone- and cytokine-dependent proliferation of endometrial cells in 3D co-culture

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-20

  preprintOpen access

  Abstract The endometrium and menstrual disorders, such as endometriosis and adenomyosis, are difficult to study, partly because menstruation depends on interactions between multiple cell types through complex molecular mechanisms. To help understand this system, researchers need humanized experimental and computational models that can interrogate how endometrial cell populations impact each other in both physiological and pathological conditions. Here, we use ordinary differential equations (ODEs) to model changes in the rates of endometrial cell proliferation and death in response to hormones, cytokines, and the specific cell types present. To calibrate this computational model, we used previous-published experimental datasets from a 3D co-culture platform supporting primary human endometrial epithelial organoids and endometrial stromal cells. Our ODE-based model can simulate the size of endometrial epithelial organoids and the density of stromal cells over time under multiple hormone/cytokine conditions in mono- and co-cultures. We further created a second, partial differential equation (PDE)-based model that simulates the diffusion of molecules added to these 3D cultures and their uptake by proliferating endometrial cells using the predicted cell densities from the ODE model as inputs to the PDE simulations. We show that the exposure to hormones and cytokines used in the experiments is reasonably homogenous throughout the 3D culture and identify conditions where this would not be true. Altogether we use these models to quantify the influence of stromal cells on epithelial cell proliferation and vice versa , to identify differences across cells from different donors, and to provide a quantitative assessment of experimental designs.

  PublisherOA PDFDOI

• Lyme disease increases risk for uterine conditions and gynepathologies 2029

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description Lyme disease (LD) is an illness caused by the spirochete Borrelia burgdorferi (Bb). Bb is known to disseminate through organs, including the skin, joints, spinal cord, bladder, heart, leading to Lyme arthritis, neuroborreliosis, and Lyme carditis. While previous studies have investigated the impact of LD on pregnancy and found the presence of Bb in the uterus of mice, we studied the impact of LD on the female reproductive tract. Using large-scale electronic healthcare record data, we report that LD additionally results in increased risk of several gynecological diseases. We use a LD mouse model and find a severe ongoing infection of the reproductive tract, in which bacteria persist in the tissue up to 15-months post-infection, resulting in glandular cysts, endometrial hyperplasia, and interspersed endometrial stromal cells. Even in C57BL/6 mice, long thought to be asymptomatic for LD, we observe uteruses infected with Bb after 8 weeks of infection, and ongoing infection throughout the next 12 months. Additionally, we find that age has an impact on the extent of gynepathology such that reproductively senescent aged mice (1-year old) have more gynepathology with infection when infected for the same length of time as young mice (15-weeks old). This work suggests that Lyme disease associated gynecological pathologies may be underappreciated and suggests further study of sex differences in the context of Bb infection. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01EB010246

  NIH · $3.3M · 2015

• Microvascular Permeability, Inflammation, and Lesion Physiology in Endometriosis: A Microphysiological Systems Approach

  NIH · $2.9M · 2019–2024

• NIH Grant R01GM059870

  NIH · $2.4M · 2008

• NIH Grant UH2TR000496

  NIH · $2.3M · 2014

• NIH Grant R29GM050047

  NIH · $544k · 1998

Frequent coauthors

• Douglas A. Lauffenburger

  Massachusetts Institute of Technology

  132 shared

• Alan Wells

  95 shared

• Donna B. Stolz

  47 shared

• Miles A. Miller

  41 shared

• Steven M. Jay

  University of Maryland, College Park

  34 shared

• Keith Isaacson

  33 shared

• Richard Lee

  32 shared

• Luis M. Alvarez

  29 shared

Labs

• Griffith LabPI

  Engineering of tissues and organs for regenerative medicine and drug discovery

Education

• Ph.D., Biological Engineering

  Massachusetts Institute of Technology

  1990

• B.S., Mechanical Engineering

  University of California, Berkeley

  1985

Awards & honors

• MacArthur Foundation Fellowship
• Popular Science Brilliant 10 Award
• NSF Presidential Young Investigator Award
• MIT Class of 1960 Teaching Innovation Award
• Radcliffe Fellow