Grand Rapids-based uterine fibroid tumor study may lead to better treatments

Feb 4, 2020

Jose Teixeira, professor in the Department of Obstetrics, Gynecology and Reproductive Biology at Michigan State University College of Human Medicine
Credit MSU.edu

"I was trained as a reproductive tract developmental biologist back at Harvard Medical School. When I was recruited here of course, I'm going to continue to study reproductive tract biology, and one of the more interesting aspects of reproductive tract biology is the fibroids it's the most common tumor and women by far and no one really knows how they start and no one really knows how they grow. I thought that that would be a really good way for me to advance our knowledge and continue the study." 

When fibroid tumors are not treated the result is what? What is the procedure that most women experience.

"So, almost all women will have fibroids. They can become problematic and then women will go to see their doctor and say I'm having these issues and the doctor will say it's because you have fibroids. The only cure at this moment is a hysterectomy which is removal of the uterus. Which, for some younger women back to be very traumatic because they're giving up their fertility. For older women, a lot of times it's not that big an issue but they still feel that having a uterus is part of being a woman and there's a lot of psychological issues associated with that." 

How many hysterectomies are performed every year in the United States?

"600,000 half of those are because of fibroids."

So, as you take a look at this what did you discover?

"There are no good medical treatment from hormonal treatments might be OK for a little while, but you don't want to put women on hormonal treatments because of other issues associated with excess hormone treatment. What we've found in this study is that the fibroids which are growing, these are sort of highly collagenous, it looks like cartilage growing inside muscle. The other tissue that's very close by to the uterus that's a lot of cartilage is the cervix. When we discover that these genes that are associated with cervical cells were found in the fibroids we immediately thought that perhaps the fibroids are turning into fibroids because they want to be more like cervical cells which is not what they should be."

How does that happen?

"We don't really know how it happens. We have some ideas. There are two major types of fibroids based on genetic alterations. We don't know what those genetic alterations actually do to make the cell behave like a fibroid, but we know it at the end these genes that are associated with being more like a cervix are up-regulated, in other words, genes get turned on when they shouldn't be."

The research was collaborative. Explain how all this work came together and to come to the results that you have so far?

"This kind of study really takes a team. We have the bench top scientists, which is my group, then we have Hui Shen, who's up the street at Van Andel Institute which I believe is the center of the epigenetic universe right now. So, we're very lucky just to have those people a few blocks away and then we have our collaborators at Spectrum Health who collect these tissues and consent each patient and allow us to get those issues that we need to make these studies happen. None of it could have been done without that kind of collaboration; we need the clinical specimens, we need the person doing the bioinformatics, and then we need the bench top scientists."

Take me through everybody's role in this and how it came together.

"The idea was one that I've been wanting to study for quite some time and often with these kinds of things you have great ideas and everybody can have great ideas. But if you don't have the tools to actually implement those ideas then it's sort of just an idea and it stays that way. But when Hui Shen, the epigenetics people moved into the Van Andel Institute a few years back I was finally in a place where hey we can do this big data type of study now and look at what might be going on, not at the genetic level because we kind of know what's going on with those genes that can mutated, but at the epigenetic level. What else is going on in those genes that isn't necessarily mutation. And then, of course, we have to have a clinical partner and we've been very lucky to have Dave Chesla over at Spectrum Health doing the clinical work for us which means you know having his team do all that consenting, collecting the tissues, anonymizing it, meaning that we don't actually get any patient information. Then, our team takes the tissue and does the basic cell isolation techniques, DNA isolation, R&A isolation, and we do the study with the big data and then with the help of the epigenetics people they do the analysis."

And now that you have some results here and the funding from the National Institutes for Health, what is next? Where do you take this study?

"We have funding to continue. This was kind of a pilot study we only have a few patients in each group because these kinds of experiments a very, very, very expensive. Now, we have enough to do 100 patients and to look at their DNA and RNA. What's nice about having 100 patients is now we can look at those two major genetic alteration and look at them separately. We'll have enough samplse to look at both separately and we'll also be able to collect enough samples from African American women and Caucasian women ans Asian women because the incident in African American women for fibroids is much higher. The reasons for that racial disparity are completely unknown. So, we're hoping that since we, meaning the field has been unable to determine any really significant genetic differences between the African American women with fibroids and Caucasian women with fibroids that it must be epigenetic. So, that's what we're going to continue with the study."