Feature Story | 9-Dec-2024

Women’s health is chronically understudied, but these Boston University engineers are charging forward

Boston University's Catherine M. Klapperich and Joyce Y. Wong are pioneering research into reproductive health issues, from uterine fibroids to preeclampsia to hormone monitoring

Boston University

Here’s a shocking fact: nearly 80 percent of all women will develop uterine fibroids at some point in their lifetime, making them the most common type of benign tumor in the reproductive system—and yet scientists still don’t know what causes them. Many people have fibroids without ever knowing it, but others experience symptoms like heavy menstrual bleeding and cramping. Scientists know that they form in the smooth muscle cells of the uterus, but that’s about it. And it’s not the only reproductive health issue with glaring gaps in our knowledge.

“Basically any tissue of the female reproductive system is understudied,” says Catherine M. Klapperich, a Boston University College of Engineering (ENG) professor of biomedical engineering. Research on women’s anatomy and pain has been underfunded for decades, meaning little is known about what’s happening at the cellular level in women’s bodies and how that impacts their health. So, answering many big questions about women’s health, from fibroids to hormone changes, starts with improving the baseline understanding about how things work—both in healthy people, and when things go wrong. Building up that research is exactly what Klapperich and her colleague, Joyce Y. Wong, are doing. 

“I want to use the tools of engineering to look at these problems in more detail and create models of reproductive tissues that we currently don’t have,” says Klapperich, who coleads the Design, Automation, Manufacturing, and Processes (DAMP) Lab

Her vision includes creating cell lines from reproductive tissues and organs—cells collected from a patient with their consent and changed in the lab so they keep replicating—that can lay the foundation for researching lifesaving treatments and diagnosing issues that occur before, during, and after pregnancy. She and Wong, an ENG professor of biomedical engineering, work side by side, co-advising a handful of students who look at women’s health through the lens of engineering. With their research partnership and mentorships, they’re building a robust library of knowledge about cellular mechanisms that can lead to disease, and eventually point to a greater breadth of solutions. Investigating fibroid tissue is just one example of starting research from the ground up. 

“If we can study fibroids starting at a cellular level with data-rich, diverse samples, we can determine potential causes and improve fibroid diagnosis and treatment,” says Lena Landaverde (ENG’13,’17,’26), a PhD student in Klapperich’s lab. As of now, there are no fibroid-specific treatments, and since fibroids have overlapping symptoms with endometriosis and menstruation, they’re difficult to diagnose. Although they’re noncancerous, it’s possible for a fibroid to conceal cancer and potentially delay treatment. Surgery to remove fibroids, called a myomectomy, is the only option to completely get rid of them, though often they reoccur. 

In collaboration with Boston Medical Center’s Fibroid Center, Klapperich and Landaverde are developing the first open-access biobank of fibroid cells—essentially a catalog of cells from real fibroid tissues that patients opted to donate after having surgery. Landaverde is starting the foundational work required to acquire samples and develop cell lines, with a specific interest in unraveling how fibroids develop. They hope to eventually provide whole genome sequences and other molecular data from the cells that can then be used by other scientists, like Wong, to more easily diagnose them and investigate causes. 

Same Cells, Different Body Parts

Studying cellular mechanics to pioneer bigger solutions to problems is how Klapperich has worked her whole career. She’s invented portable devices for testing for sexually transmitted infections, including chlamydia and gonorrhea, with a focus on point-of-care diagnostics—meaning the tools can be used anywhere, putting the power of medical testing in the hands of patients. Similarly, Wong has wielded her expertise in cell biology and materials science to make diagnostic and therapeutic innovations, including improvements to medical imaging using the tiniest of particles, called nanoparticles and microbubbles. These particles could be engineered to bind with different types of smooth muscle cells, like fibroids, and can raise alarm bells for doctors needing to confirm their location.

Nanoparticles and microbubbles are “types of biomaterials that can enhance imaging and can provide a marker that can be seen with ultrasound, or with magnetic resonance imaging,” Wong says, which is an essential step in being able to diagnose fibroids and much more. She is also using microbubbles and nanoparticles to detect and treat postsurgical adhesions, an inflammatory disorder that commonly forms after surgeries like a cesarean section and can cause severe pain and problems with later pregnancies, including infertility. As of now, the only way to confirm adhesions is to perform another surgery, Wong says, which can then cause additional adhesions to form. 

Wong first studied smooth muscle cells in other parts of the body—like in the walls of blood vessels—before shifting to focus on reproductive tissue. “The remarkable thing about smooth muscle cells is that they have the capacity to change their function and change their behavior depending on the context, like pregnancy,” she says. One of Wong and Klapperich’s students, Isabella Claure (ENG’24), is investigating issues like how different levels of hormones influence the uterine smooth muscle cells, and what kinds of mechanics are at play when they’re stretched during pregnancy.

“Before giving birth, these cells shouldn’t contract, because that could lead to preterm birth. Then after giving birth, they need to contract again, otherwise the lack of contraction could lead to hemorrhage,” Wong says. With hemorrhaging, or excess bleeding, being one of the leading causes of preventable pregnancy-related deaths, understanding these dynamics is crucial for improving pregnancy outcomes.

Another one of their PhD students, Sebastian Naranjo (ENG’24), is looking into an underlying mechanism that leads to preeclampsia, a serious high blood pressure condition that impacts about 8 percent of all births in the US and causes about 15 percent of premature deliveries. With Wong and Klapperich, he’s developing a model in the lab that mimics how, during the second and third trimesters of pregnancy, smooth muscle cells in the arteries are replaced by placental cells—fundamentally restructuring the blood pathways to the uterus in order to bring nutrients to the fetus. It’s thought that a dysregulation of how the placenta forms is the most prevalent cause for preeclampsia. But there are currently no models that emulate this process.

“Why don’t we know more about this? We just haven’t studied it closely enough,” Klapperich says. 

Elevating Women’s Health Research 

In pursuit of more answers, Klapperich is expanding the team’s constellation of collaborators. She most recently won funding from the Massachusetts Life Sciences Center Women’s Health Collaboration Program to install a state-of-the-art Abbott diagnostics machine that can analyze blood and tissue samples in a medically ethical, HIPAA-compliant way. With this instrument—which is so large it requires a renovation of the lab and special training to operate—Klapperich will begin working with health technology company BioSens8, which developed a hormone monitoring platform using biosensors that are sensitive to hormone molecules. It was founded at BU by James Galagan, an ENG professor of biomedical engineering, and Uroš Kuzmanović (ENG’23), now the company’s CEO. Their biosensors could be used to continuously monitor hormone fluctuations, like estrogen and progesterone levels, at different phases of fertility to know the ideal timing of administering treatment for in vitro fertilization (IVF). 

“For IVF and other assisted reproductive technologies, women are typically getting blood tests daily, for days or weeks, to track their hormones and to have the best possible outcome,” Klapperich says. “BioSens8 is creating a platform, similar to a glucose monitoring patch, to measure hormones in real time.” Eventually, this could eliminate the need for time-consuming blood tests at a doctor’s office and simplify the process for those trying to conceive. Using the DAMP Lab’s new tech, Klapperich and the BioSens8 team will soon be running clinical testing to evaluate how well the patches work compared to the current standard. 

“Hormones are part of our lives and regulate a lot of things, like melatonin in sleep and cortisol in stress, so this technology could be used in a wide variety of ways for women’s health,” says Klapperich.

There is so much to learn about how the hormone cycle and reproductive system are interconnected. But with more and more experts like Klapperich and Wong focusing on women’s health, many unanswered questions can finally begin to be understood—to improve and save lives. 

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