Engineering a cure

When Linda Griffith’s 12-year-old niece started suffering from unbearable abdominal pain a few years ago, Griffith felt pangs of sympathy — and déjà vu.

Griffith was also 12 years old when she first felt the pain of endometriosis, a disease caused when tissue similar to the lining of the uterus grows outside the uterus, usually attaching to the lining of the abdominal cavity or ovaries. She went to doctor after doctor, some of whom tried to tell her that she was suffering from “too much stress,” she recalls, until she was finally diagnosed at the age of 28 during surgery.

Since then, Griffith, a professor of biological and mechanical engineering, has had nine surgeries including a hysterectomy but still suffers from recurrence of the disease. Now, she and colleagues at MIT and Harvard Medical School are launching a new center to investigate endometriosis, which is often linked to infertility and is estimated to affect at least 5 to 10 percent of women around the world.

The Center for Gynepathology Research will target the disease from a biological engineering perspective, in hopes of developing better tools to study disease mechanisms and better platforms for developing drugs. Griffith also hopes the new center will help raise awareness of endometriosis, which is often misdiagnosed.

To celebrate the launch of the center, Padma Lakshmi, host of Bravo’s “Top Chef” program, will speak at MIT on Friday, Dec. 4. Lakshmi will talk about her own struggles with endometriosis.

“A lot of women do have these gynepathologies, and there’s not an enormous research community addressing them,” says Griffith, who is on sabbatical this year at Harvard’s Radcliffe Institute for Advanced Study. “There’s certainly not much engineering effort directed at the biology of the disease — engineers have until now mainly focused on developing surgery tools.”

A new direction

Around the same time that Griffith’s niece, Caitlin, first started to get sick, Griffith began thinking about her research in a new way.

She started her career as a chemical engineer, but joined MIT’s fledgling Division of Biological Engineering in 1998. There, she focused on tissue engineering, designing scaffolds on which cultured cells can grow and form new bone or liver tissues.

In 2007, Griffith was asked to participate in a panel discussion highlighting work of women scientists. As she was preparing for the discussion, she was asked if she could talk about how her research specifically benefits women, a question that stumped Griffith. “I had never thought about my research in that way,” she says.

For the first time, she started to consider endometriosis and other gynepathologies as potential research targets. During the panel discussion, she “blurted out” that she would like to start a research program in endometriosis within the next three years.

She got another nudge from her own surgeon, Keith Isaacson of Harvard Medical School and the Center for Minimally Invasive Gynecologic Surgery at Newton-Wellesley Hospital. 

Isaacson was familiar with Griffith’s work in tissue engineering and thought she could bring a fresh approach to endometriosis research, which has moved at a very slow pace in recent years. “We haven’t made any major advances in the last 20 years,” he says.

Part of the reason for the lack of progress is that there are no good animal models for endometriosis. Using tissue engineering, Griffith and her collaborators hope to create a tissue model that can be used in the lab to study how the disease originates and progresses, and combine that with systems biology analysis of the peritoneal fluid environment.

“We know so little about how the disease starts, and very little about how it progresses,” says Griffith, who won a Transformative R01 grant from the National Institutes of Health earlier this year that will help fund her work at the new center. “We want to illuminate the mechanisms and thereby illuminate places where you may intervene to develop therapeutics.”

Other projects will look at the effects of low-dose radiation on endometrial cells, imaging of endometrial lesions, and development of new surgical tools for removing uterine tissues. Much of the center’s funding comes from an anonymous donor, with additional funds from MIT’s School of Engineering and the NIH.

Better treatments needed

Current treatments for endometriosis usually involve manipulating hormone levels, which Isaacson describes as a “crude” approach. Birth control pills can help by halting ovulation and slowing down growth of endometrial tissue, but if that doesn’t work, patients can take stronger drugs that essentially induce menopause (which brings unpleasant side effects).

Another drug, a steroid called Danazol that lowers estrogen levels, worked well for Griffith but caused her to gain 20 pounds in two months.

“They say you shouldn’t take it for more than six months, but I took it for two years, to get me through tenure,” she says. “For women who don’t respond to birth control pills, the other treatments have really severe side effects, and they’re not always effective in controlling symptoms.”

Many women with endometriosis experience infertility, including Griffith, who underwent unsuccessful fertility treatments. Severe cases of endometriosis usually require repeated surgeries to clear out tissue that continues to build up, and surgery is also the only way to definitively diagnose the disease.

That’s partly why many cases, like Griffith’s and her niece’s, can go undiagnosed for years. Griffith’s experience with endometriosis made it all the more painful to watch her niece — whose disease was identified four years after she first had symptoms — go through the same thing, under the care of a female Ob/Gyn who insisted Caitlin’s problems were stress-related even after hearing of her aunt’s clinical history.

“It was very hard because not only was Caitlin re-living the worst part of my high school experience, I was trying to prevent it from happening and I couldn’t,” she says. “Women are just not getting diagnosed with these problems.”