Pictured above: MIT Assistant Professor Sixian You (right) and a colleague in MIT’s Computational Biophotonics Lab
MIT’s Center for Gynepathology Research (CGR) is embarking on an ambitious project titled “A New Vision for Endometriosis, Adenomyosis, and Infertility Research,” made possible by a generous grant from The Manton Foundation. The funding supports the CGR’s ongoing work in building living patient avatars for endometriosis and other diseases. It also enables three new investigators with powerful approaches in imaging and infectious disease immunology to join the CGR team.
“This project represents a major leap forward in our ability to study these debilitating diseases,” said Linda Griffith, CGR Director and Professor of Biological and Mechanical Engineering at MIT. “With the support of The Manton Foundation, we are now able to study disease mechanisms and responses to treatments in ways that have never been possible before.”
Transforming Research with “Living Patient Avatars”
The funding will further the development of “living patient avatars”—advanced 3D culture systems designed to replicate the unique cellular and molecular environment of individual patients. The avatars are powered by synthetic extracellular matrix (ECM) technology that Dr. Griffith’s lab has pioneered, providing an unprecedented ability to study tissue interactions and test therapies in real time.
A breakthrough came last year when CGR researchers successfully co-cultured human endometrial organoids and stroma in a synthetic hydrogel extracellular matrix. This innovation supports the growth and interaction of different cell types in a dynamic 3D environment, simulating the effects of hormonal changes with greater precision and reproducibility. Laboratories worldwide have adopted this platform, and it is already influencing pharmaceutical testing for new non-hormonal treatments. (See details in this published article on the organoid culture model.)
“These models allow us to go far beyond traditional methods,” Griffith explained. “We can observe how different cells communicate, study disease progression, and test potential treatments in a highly controlled yet biologically relevant setting.”
Human endometrial epithelial organoid (blue nuclear stain and green actin stain, center) growing in “Magic Matrix” with endometrial stromal cells (red vimentin cytoskeletal stain). ”Magic Matrix” took about 10 years to develop, through extensive engineering design around the way cells interact with their in vivo environments, combined with polymer science. Cells are encapsulated in the matrix and then remodel it to become more like the tissue of origin, allowing cells to send signals to each other in response to hormone and other environmental changes.
Pioneering Advances in Imaging and Immunology
A key component of the new project is the application of multi-photon label-free imaging. It uses finely-tuned laser light to excite fluorescence in tissues without staining. Researchers in MIT’s Computational Biophotonics Lab, led by Professor Sixian You, have begun using this imaging technique to analyze endometrial biopsies. Their work has uncovered intriguing biological structures such as Nuclear Channel Structures (NCS) that could be linked to fertility issues.
“This imaging approach is opening doors we never knew existed,” Griffith said. “With the Manton Foundation’s support, we can apply these techniques to living patient avatars and observe their biological responses in real-time over weeks of culture.”
The foundation’s funding will also support the construction of a new, more advanced microscope and the involvement of students in imaging studies. This infrastructure will not only enhance MIT’s research capabilities but also create valuable tools for the broader gynecological research community.
Exploring Links Between Infectious Diseases and Women’s Health
A particularly exciting aspect of the project involves investigating how prior infectious diseases, such as Lyme disease, may predispose women to gynecological conditions like endometriosis. This hypothesis, based on emerging evidence from large databases such as the UK Biobank, suggests that certain infections might cause chronic immune responses that trigger gynecological disorders.
To explore this theory, researchers will use a nascent technology called “x-FLIP” that probes blood and saliva to detect immune reactions to environmental antigens. The goal is to refine and automate the assay for broader application. These studies could lead to entirely new treatment models, potentially extending beyond gynecology to other chronic inflammatory diseases.
Project team member Bryan Bryson, an MIT Professor in Biological Engineering, specializes in the systems biology of the innate immune system in infectious disease, and his lab is the CGR’s main collaborator for the immune components of the patient avatars used for endometriosis and the endometrium. Bryson is also a core member of the Ragon Institute of Mass General, MIT, and Harvard.
Multiphoton label-free imaging of human early luteal phase endometrium. Epithelial cells are yellow (metabolic marker ) and collagen supporting tissue is green due to second harmonics. Pink represents interfaces, which can indicate a variety of different structures including immune cells. The arrow points to a special organelle in the nucleus, the nucleolus, which moves around relative to the nuclear membrane at different parts of the cycle.
A Bright Future for Biomedical Innovation
This initiative reflects the CGR’s commitment to advancing women’s health through interdisciplinary collaboration and technological innovation. Griffith highlighted the far-reaching potential of the research, saying, “By focusing on gynecological applications, we’re not only shedding light on these often-overlooked disorders but also developing technologies that will benefit many other fields of medicine.”
“Collaboration from experts like Eliezer Calo, Professor of Biology at MIT, Brian Bryson, and Sixian You positions CGR to tackle some of the most pressing challenges in women’s health,” Griffith explained. “This project is not just about advancing science—it’s about delivering meaningful, patient-centered results.”
“With the support of The Manton Foundation, we’re making strides not only for gynecology but for the entire field of medicine,” Griffith said.
