Explore how we solve problems in cancer, women's health and gut health!
What happens to cancer when tissues move?
Research themes: Cancer, women's health, mechanobiology
Cells sense mechanical cues around them, and convert their mechanical environment into biochemical signals. The colon and the uterus are highly mechanical organs, moving constantly to shift fluid/food and expel waste. Tumors in these organs therefore experience the mechanics of colonic or uterine movement, called peristalsis. We do not have a good understanding of how peristalsis specifically alters cancer progression. In order to tackle this problem, we invented a new peristalsis bioreactor which allows cells in lab to experience the complicated mechanical patterns of peristalsis. The bioreactor can be tuned to mimic mechanics of the colon or the uterus! In colorectal cancer, our work established the first experimental link between colon mechanics and cancer risk, offering actionable insights into leveraging diet to control cancer. We hope to extend our findings to understand immune evasion, so we can improve immunotherapy outcomes in the future!
This work is funded by the Cancer Prevention and Research Institute of Texas and the National Science Foundation CAREER Award.

Why do metastatic cancers hide for years in the body and suddenly cause cancer relapse?
Research themes: Cancer, Tissue Engineering
Metastatic cancer causes >80% of cancer deaths. When cancer moves out of its original location and metastasizes, it also becomes resistant to chemotherapy. There are no good ways to treat metastatic cancers currently. The Raghavan lab hypothesizes that the extracellular matrix architecture of livers promotes dormancy which allow cancer cells to hang out for decades microscopically, avoiding detection. To understand how architecture fuels dormancy, we employ tissue engineering methods - first we create a liver scaffold that is engineered to mimic the architectural complexity of the liver; next we tissue engineer microscopic tumor "seeds". When we combine the two, we engineer a microscopic metastasis that replicates many biological processes including chemoresistance. This platform fuels the discovery of new therapeutics to stop metastasis!
This research is funded by the NIH National Cancer Institute through an R37 MERIT award.

How can we restore colon mechanics using tissue engineering and novel therapeutics?
Research themes: Gut Health, Immunology, Tissue Engineering
When our gut doesn't move like it's meant to, it disrupts our quality of life by impacting everything from digestion to waste expulsion from our body. Colon mechanics are disrupted in many conditions including Irritable Bowel Syndrome (IBS), Crohn's disease, and Gulf War Illness. Service-related toxic exposures in combat veterans leads to chronically impaired colon mechanics in Gulf War Illness. Our work was the first to discover the role of macrophages, a population of immune cells, in promoting Gulf War Illness. Immune cells like macrophages fan the fires of inflammation, directly impairing nerve regeneration and therefore gut movement. In order to test new therapeutics to improve colon mechanics, we developed immune competent bioengineered colons in the lab - these engineered colon tissues produce peristalsis mechanics like the native colon that we can impair with toxic exposures. Using tissue engineered colons, we hope to find new therapeutics to improve the quality of life of Gulf War veterans!
This research is funded by the Department of Defense by the Toxic Exposures Research Program.

How does the uterus know when to produce mechanics, and when to stay quiet?
Research themes: Women's Health, Mechanobiology
The uterus is a highly mechanical organ - moving constantly and producing peristalsis mechanics. Made up of thick muscle layers called the myometrium, the uterus is highly responsive not just to hormones but also mechanical stimuli (like stretch in pregnancy). Failure to produce correct patterns of mechanics results in endometriosis, adenomyosis and severe dysmenorrhea (painful periods and menstrual cramping). During pregnancy, labor and delivery, improper mechanics has devastating consequences on the health of the mother and neonate. Using tissue engineering principles, we engineered the uterine myometrium to produce uterine peristalsis in the lab. Using the tissue engineered myometrium, we hope to discover what regulates uterine mechanics with implications in preventing preterm birth and postpartum hemorrhage. By leveraging our patent-pending peristalsis bioreactor, we also apply the mechanics of the uterus to the cells of the inner lining to ask: how do abnormal mechanics result in painful periods and adenomyosis?
This work is funded by the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Science Foundation CAREER Award.
