By: Aaliyah Plummer, SWHR Communications Intern
Linda Griffith, PhD is a bioengineer currently working as a Professor of Biological Engineering and the Director of Gynepathology Research at Massachusetts Institute of Technology (MIT). Her decades-long involvement in the field of tissue engineering has led to breakthroughs in 3D printing cells, liver health, and now uterine health. In recent years, Dr. Griffith’s research has allowed her to advocate for a disease that she and approximately 190 million other individuals around the world navigate daily – endometriosis. Her creation of new ways to culture complex uterine organoid-stromal tissues paves the way for more direct and individualized approaches to treatment for gynecological disease. Soon after Dr. Griffith’s inclusion on the 2024 TIME 100 list, SWHR interviewed Dr. Griffith to learn more about her background in research, her journey with endometriosis, and her hopes for the future of gynecologic disease research. The following blog post captures highlights from the conversation and has been edited for length and clarity.
Tell us about your early experiences in research and how you began studying endometriosis.
I was trained as a chemical engineer. Although I originally aimed to go to medical school, by senior year, I found engineering graduate school a more attractive path. I got involved as a post-doc in tissue engineering by working with a liver transplant surgeon, which was really exciting. I then began a faculty career in regenerative medicine, working with biomaterials and 3D printing. I started appreciating that there’s so many liver diseases we don’t understand. Why would you want to replace a liver when it gets too broken? Why not cure the disease behind it?, I would ask myself. I soon started working on little microfluidics reactors to grow 3D mimics of human liver, and we commercialized something called the liver chip, which is now popularized for related research. This whole process got me interested in modeling human diseases with tissue engineering in the lab based on patient samples.
At the same time, research has always been personal to me. Not long after creating the liver chip, I had surgery for recurrent endometriosis after having seven prior surgeries including a hysterectomy. The surgeon who operated on me encouraged me to gear my research towards endometriosis, and, in 2009, my husband Doug Lauffenburger and I began our work together with Keith Isaacson (clinical director for MIT’s Center for Gynepathology Research). At the time, I also had a family member going through the early stages of an endometriosis diagnosis as well, and I watched her experience the same symptoms that I had as a young girl; I had endometriosis symptoms in my early teens and was gaslit out of a true diagnosis until I was 28.
Finally, it was my diagnosis with triple-negative breast cancer in 2010 that fully turned my interest to how diseases operate on a molecular basis. Within less than a week of finding a tumor myself, I was sitting in the office of an excellent breast cancer surgeon at Massachusetts General Hospital, planning out the surgery based on a molecular understanding of my cancer. I took this example back to Doug and my team; we speculated that there’s probably molecular subtypes of endometriosis and speculated on how we can find them. It’s never easy to get funding for gynecological research, but I was well-established by this time and had a pretty good track record with successful outcomes of prior research in other areas, so we were successful in obtaining a foundation grant to fund our initial work . Soon, our first studies on the molecular level of endometriosis were around trying to understand some of the molecular heterogeneity in the disease so patients could be stratified, and we could one day develop better therapeutics individualized for each disease type and patient.
What was your first major endometriosis research breakthrough?
One of the most exciting breakthroughs in our early endometriosis research was discovering that Jun kinase (JNK), a signaling molecule, was controlling crucial features of invasion and inflammation in endometriosis. There was a scientist at a large pharmaceutical company that was also studying Jun kinase inhibitors for a different disease, and he repurposed the drug to show it worked in two preclinical animal models of endometriosis; however, the drug did not meet the clinical endpoints in a human clinical trial. We knew we needed to eventually get to humanized preclinical models, so we worked to develop better in vitro models of the disease that we could study. My team received a Defense Advanced Research Projects Agency (DARPA) grant in 2012 that gave us enough funding to build a tissue-engineered endometrium, including invention of a new synthetic extracellular matrix that is now being commercialized, as well as conducting research to improve our microfluidic platform technologies. We also received grants from the National Institutes of Health (NIH), to build microfluidic models of endometriosis lesions complete with microvasculature, using patient-derived cells. We are now using these human “patient avatars” to study new inhibitor molecules developed by an industry collaborator. It took 15 years, but it’s finally a full circle moment of finally studying JNK in an all-human endometriosis model.
What do you think is most promising in the field of endometriosis research?
Finally, finally, finally, finally endometriosis is starting to be recognized as a pediatric and adolescent disease. I had lava shoot out of my head when a close family member of mine was ignored as a preteen then teen with endometriosis symptoms just because the textbooks say the typical endometriosis patient is in her late 20s to early 30s. There is growing appreciation for the adolescent implications of endometriosis among some leading researchers, but sadly I find that the majority of practicing clinicians still think it is a disease of adult women. The current president of the World Endometriosis Society, Stacey Missmer, and her collaborators have been especially effective in demonstrating the clinical prevalence of peri-menarchal endometriosis and getting the word out. They have been tireless in building research tools but also in forcing people to appreciate that, especially for women who develop severe disease later, the disease probably started in their early teenage years. In related studies, Frank Tu and Kevin Hellman in Chicago have been imaging uterine contractions in young girls with and without period pain, to understand why some develop period, and they envision future studies to illuminate links between period pain in young girls and development of endometriosis. By studying adolescent populations in a thoughtful way, we are going to learn a lot more.
Learn more about the symptoms, diagnosis, and treatment of endometriosis in teen populations in SWHR’s Endometriosis Toolkit: A Guide For Teens toolkit. The resource is also available in Spanish, Kit de Herramientas para la Endometriosis: Guía para Adolescentes.
Where do you see the field of endometriosis research going in the next five and next ten years?
First, it is important to underscore that adenomyosis – the sibling condition where endometrium-like tissue is found in the uterine muscle – should always be included in discussions of endometriosis research. About two thirds of patients diagnosed with endometriosis are stage I or stage II, and many surgeons are starting to question whether the dominant symptoms in these patients might arise from the uterus itself, and not endometriosis, as there is much overlap in diagnosis of endometriosis and adenomyosis in the research literature. Adenomyosis remains notoriously underappreciated and understudied. Much of our current work includes tissue-engineered models of adenomyosis and examination of lesions from patients.
With that perspective on the clinical landscape, looking towards the scientific landscape, I think we’ll see more people from different fields like infectious disease, immunology, and nutrition coming up with new ideas and probing very thoughtful, thorough collaborations when it comes to endometriosis diagnosis and care. My clinical collaborator, Dr. Isaacson, started a gynecology surgery conference of a very special nature at MIT back in 2015, the “Open Endoscopy Forum”. Each year, people come out for a weekend of TED-like Talks from leaders in the field, mostly surgeons and scientists from MIT. It’s been a magical experience, and it’s a way to convene the enormous spectrum of people from different fields to think blue-sky about the future. Part of what it has done is catalyze engineers to bring new tools, ideas, and energy in the field of endometriosis. In fact, MIT is about to launch a “Mars Shot for Menstruation Science: Ground Zero for Women’s Health” (with appreciation to former NIH Gynecology Branch Chief Lisa Halvarson for coining “Menstruation Science”), with philanthropic funding, to help us improve our tools for patient avatars and to get them out to other researchers. I think we’ll see more of this innovative thinking in the future, and as we do, we’ll see better research and better treatment for individuals living with endometriosis.