Science at Work

Michelle Monje '98

By Julia Van Develder

A Ray of Hope

Diffuse intrinsic pontine glioma—chances are you’ve never heard of it. It’s a highly aggressive, malignant brain tumor that typically arises in children between the ages of five and nine.

“It’s rare in terms of the whole population,” says Michelle Monje ’98, MD-PhD. “There are probably 600 new cases a year in the United States. But it’s one of the more common types of pediatric brain tumors, and it’s a disease that we’ve made no progress in treating in over 35 years.”

A neuro-oncologist at Lucile Packard Children’s Hospital at Stanford University, Monje is determined to change that. When she was a medical student at Stanford, she took care of a nine-year-old girl with diffuse intrinsic pontine glioma (DIPG). “I absolutely loved this patient,” says Monje. “I took care of her from the beginning of her course, from the diagnosis until her death. And I was just so frustrated that we had nothing we could offer her. It’s a terrible disease, and it’s one we can temporize for a brief time, but then it inevitably and inexorably progresses, and the child usually dies within a year. I promised myself that when I came back for residency, I was going to start focusing on it, and it really was this one patient who inspired that.”

The reason so little progress has been made in developing a treatment for DIPG has to do with the nature of the tumor. It grows within the brain stem, rather than on it, and specifically in the pons, the part that controls critical functions, such as breathing. It can’t be removed or even biopsied without doing irreparable damage—so scientists haven’t had the opportunity to study it. Until now.

Dylan Jewett was five years old when he was diagnosed. He and his family had just recently moved to Guam, where his father was stationed at Anderson Air Force Base. His mother noticed what she thought were minor coordination problems and scheduled a checkup. But before they could keep the appointment, the Jewetts found themselves in the emergency room with a child who was barely conscious.

By the time he was transferred to Lucile Packard, Dylan was at an advanced stage of the disease. “He was already bed-bound and had really severe neurological consequences of the tumor,” says Monje. “The family made the decision that the best thing for him was to make sure he was comfortable, rather than putting him through a course of radiation therapy that was unlikely to change the course of his disease. So Dylan died approximately five weeks after I met him.”

Knowing that their son’s death was imminent, Dylan’s parents approached Monje and offered to donate his tumor. “It was an incredibly generous gift,” says Monje. “I’m a mother—I can’t imagine being so selfless in the midst of such a terrible tragedy. But they said they didn’t want anyone else’s child to have to go through this.” 

Monje began to prepare for the donation, assembling a team to harvest the tumor in the early postmortem period and begin culturing the cells. Within a matter of weeks, her lab had a thriving culture—the first cell culture of DIPG in the world. “When I came to this project, there was no experimental model system available, no available cell culture of this tumor, no effective animal model. And beginning with Dylan’s donation, we were able to culture this tumor, grow it in the lab, and establish a tumor cell line that we can now transplant into animals. We now have a xenograft model, so we can study the tumor both in a dish and in a mouse. We can ask questions about what it is that makes these tumors grow, what kinds of drugs might inhibit their growth, and what treatments might be effective.”

They also now have a resource to share with other researchers working on this tumor. “We are very happy to share with any researcher who is studying this tumor. One of our collaborators has already established a therapy for a different kind of tumor, glioblastoma, and they have found that it’s relevant in this disease as well, and we’re opening a phase-one clinical trial of this treatment in our patients this year, which is really exciting. Because this is such a devastating tumor with such limited treatment options, we are able to rapidly translate any findings in the lab quickly into a clinical trial. So we’re hoping to make some real progress for our patients in a much shorter time frame than we typically can with other diseases.” 

From the time Michelle Monje ’98 was in grade school, she loved science—she went to special science camps and excelled in science at school. But when she got to high school, she unfortunately got stuck with a sexist biology teacher. “I wasn’t doing as well as I usually did, and I thought maybe I wasn’t studying the right way. I went to him and asked how to do things better so that I could succeed in his class. And I remember very clearly him saying to me, in a polite but somewhat condescending way, ‘Don’t worry, sweetheart—it’s the rare woman who has a mind for science.’ And I thought, oh, okay, I guess this isn’t for me, then—not really even understanding the magnitude of what he had said.” 

She came to Vassar expecting to major in English, but still feeling the pull of the sciences. She met with her freshman advisor, biology professor Kate Susman. “She looked at my transcript, and said, ‘So what was the deal with biology?’ And I said, ‘Well, I just think I don’t have a mind for science.’ And she looked at me and said, ‘Where did you hear that?’ I told her, and she got really mad. I hadn’t understood that what he said was so deeply wrong until Kate reacted the way she did.

“I don’t think I would have gone into science and medicine if I hadn’t gone to Vassar,” Monje says. “I think I would have been discouraged had I gone to a larger university where I didn’t have that kind of mentoring relationship. I feel like Kate saved me. She put me back on the path I wanted to be on, and it has worked out very well. And she continues to mentor me. I just saw Kate this last year. She came out to the Bay Area, and we took my then-nine-month-old out for the day. We talked a lot about how to achieve balance between being a good mom and being a professional woman and a scientist—how to deal with being torn in all those different directions and still do at least some of it well. It’s really a tough balance.”

The balance between clinical practice and research, on the other hand, is gratifying, Monje says. “Given a specialty like neurology, I’m so glad that I did the PhD. Certainly the training was invaluable, and I really love the balance of doing both. In my clinical field, it would be incredibly frustrating for me if I didn’t feel that I was able to work on the problems that we grapple with on a basic science level, as well as taking care of patients.”