Grant to further pivotal research in uterine diseases
Dr. Shreya Raghavan is pursuing new foundational knowledge of the human uterus and the diseases that affect it with the help of an illustrious CAREER award from the National Science Foundation.
Dr. Raghavan and her researchers. Front row, left to right: Karla Ortega Sandoval, Dr. Shreya Raghavan, Lucia Nash. Back row: Dr. Shalini Kirthi Vasan, Abigail McCollum, Dr. Astha Lamichhane.
Pelvic pain, menstrual cramping and abdominal discomfort may be signs of a serious disease of the uterus such as adenomyosis or endometriosis, fibroids, or even endometrial cancer. Thousands of women in America suffer from these conditions, all of which have one thing in common: altered, pathological cell behavior.
In endometriosis, cells from the lining of the uterus spread to form lesions in other areas of the body. In adenomyosis, they grow into the muscle wall of the uterus. The result of these diseases is a lifetime of chronic pain and potential infertility.
“At least one in 10 women suffer from endometriosis or adenomyosis, severely impacting quality of life,” said Dr. Shreya Raghavan, a professor of biomedical engineering at Texas A&M University. “But we know very little about the nonpregnant uterus. Research in this area has been historically underfunded and very understudied.”
Raghavan is working to fill that gap in scientific knowledge, thanks to an illustrious CAREER award from the National Science Foundation (NSF) and a cutting-edge device developed in her laboratory.
CAREER grants are the most distinguished award that the NSF can give to junior faculty. They recognize great contributions to both science education and the foundational knowledge of science as a whole.
Raghavan believes that the key to understanding uterine diseases may lie in cyclic muscle contractions, called peristalsis, which the uterus continuously performs. Peristalsis has been studied extensively in other organs of the body, such as the colon, but remains largely unstudied in the function of the uterus outside of pregnancy.
“When someone hears peristalsis, they usually think of the gut and digestion, like the way the colon moves,” Raghavan said. “But peristalsis is a mechanical pattern that exists in many smooth-muscle organs. In fact, it’s very central to the function of the uterus. If it doesn’t produce these propagating waves, there’s no menstrual cycle, there’s no fertility, and there’s no labor. In conditions like endometriosis or adenomyosis, or even infertility, MRIs reveal that these mechanical patterns dramatically shift.”
We know very little about the nonpregnant uterus. Research in this area has been historically underfunded and very understudied.”
The peristalsis bioreactor up close.
Strain, such as the wavelike forces generated by peristalsis, alters the chemical signals cells send one another — and ultimately cell behavior. When endometrial cells become cancerous or leave their location and begin forming lesions in other parts of the body, that change in behavior is sparked by something. Raghavan believes that it may be aberrations of the peristalsis wave pattern that lead to the abnormal cellular behavior.
Previous investigations into the peristalsis of the uterus and its effect on cells have significantly simplified the complex cyclic strain and stress patterns. In a laboratory, it’s much easier to generate forces like stretching or skewing in a single direction, but on their own, these simplified forces do not accurately mimic the entirety of peristalsis or the effects it has on cells.
Raghavan is avoiding this reduction with a new device called a peristalsis bioreactor. She and her fellow researchers have engineered it to closely model the complex wave patterns of peristalsis in the uterus, including both healthy peristalsis and the altered mechanical patterns that arise in conditions like endometriosis or adenomyosis.
“We now have the ability to externally apply uterine peristalsis mechanics to cells within the uterine endometrium, to isolate and uncover how mechanics alter cellular behavior like motility, invasion and inflammation,” Raghavan said. “Without this invention, you couldn’t ask if mechanical dysregulation is the reason for so many diseases. Now, we can get to the heart of what uterine mechanics do in terms of physiology.”
Gaining new foundational knowledge is only half of what Raghavan is pursuing with her new CAREER grant. The other half is sharing that knowledge with the public in a way that empowers change.
The peristalsis bioreactor accurately replicating the forces generated by uterine peristalsis.
“If I’ve never made an attempt at outreach, if I’m not communicating with the public in accessible, jargon-free language, why should somebody working down the street from me trust that what I do benefits them?” Raghavan said.
Raghavan is addressing this lack of knowledge with outreach at every level, from conventions like last year’s ElevateHER conference and informational booths at public events to grade school programs like AggieSTEM’s Immersion into Biomedical Engineering. She will also teach a cancer bioengineering course, dedicated to research and mechanics like those currently being studied at the Raghavan lab.
“The CAREER grant doesn’t just go to a researcher, it goes to a researcher that can integrate research and education,” Raghavan said. “Students need to learn how to communicate what they’re learning in the lab to communities. In patient populations that may say, ‘I don’t trust this health intervention,’ how do you build that trust? I actually have patient advocates come to class to talk about what they do in the community, so everyone can appreciate the benefits of federally funded science and how it works for them.”
With more programs to come and numerous laboratory experiments to complete, Raghavan and her fellow researchers are hard at work bringing awareness and foundational knowledge to a previously understudied field — knowledge that could one day change the lives of millions of patients.
