Mikaela Stewart, an assistant professor of biology in Texas Christian University’s College of Science & Engineering, is on a mission to further cancer research.
Stewart began researching mutation of the Breast Cancer gene 1, wanting to understand why someone with a mutation of the gene faced a higher risk of breast and ovarian cancers, but not other cancers. Her interest in these genetic mutations led her to a postdoctoral fellowship at the University of Washington, where she worked alongside Mary-Claire King, the pioneering scientist renowned for her mid-’90s discovery of Breast Cancer gene 1, commonly called BRCA1.
Stewart then came to Texas Christian University in 2017, where she discovered the role of estrogen in women carrying a mutated gene, which can wreak havoc in women carrying a mutated BRCA1.
“For someone with a BRCA1 variant, estrogen can essentially act like a pair of scissors, cutting a person’s DNA,” Stewart said. When DNA damage goes unrepaired, the cells, over time, can become cancerous.
In 2018, Stewart, King and structural biologist Rachel Klevit discovered the role of a partner gene that binds to BRCA1 in preventing breast cancer. Stewart’s recent research at TCU indicates that when a healthy Breast Cancer gene 1 and a healthy partner gene are bound together, they decrease the amount of damaged estrogen-harming DNA.
“The importance of this discovery is that it allowed us to narrow down which of the many functions of BRCA1 are most likely contributing to its ability to prevent cells from becoming cancerous,” Stewart said.
Klevit, the Edmond H. Fischer/ WRF Endowed Chair in Biochemistry at the University of Washington School of Medicine, said Stewart’s research gives the scientific community a possible hypothesis for the strong link between inherited mutations in BRCA1 and cancers in the estrogen-sensitive breasts and ovaries. Studies proving how removing ovaries reduces the risk of women getting breast cancer almost as much as a double mastectomy were what spurred researchers, including Stewart, to scrutinize estrogen’s role in cancer.
In fall 2019, Stewart began working alongside Eric Simanek, the Robert A. Welch Chair of Chemistry at TCU. Their collaboration, which Stewart said is complementary to her main avenue of research, is funded by a four-year grant that the National Institutes of Health renewed in September 2023 for three more years. Unlike Stewart’s work on the BRCA1 variants, her collaboration with Simanek is looking at ways to short-circuit cancers in people who don’t have acquired or inherited mutations.
The unique molecules made in Simanek’s lab are designed to prevent proteins from coming together with their partners, keeping cancer cells from growing. Each contains enough protein properties to fool a real protein into binding with it instead of joining with the partner it needs to function.
Simanek’s lab is making the potential pharmaceutical molecules, and Stewart’s lab tests those molecules to see if they bind to important proteins involved in the cancer cycle, which might lead to new therapies to kill cancer cells.
But it isn’t just about their research — it’s also teaching the next generation of scientists so that medical therapies can continue to evolve. Stewart, who chose TCU because she could split her time between research and teaching, involves students in research.
“I’m always very motivated by the idea that there’s always more to discover if we can figure out the best questions to ask,” Stewart said. “While I can’t achieve this alone or maybe even in my lifetime, the folks I train will keep helping to unfold the many mysteries that remain.”
Stewart’s passion for teaching in addition to her abiding interest in research has long impressed Klevit.
“Training undergraduates is a huge investment of time,” Klevit said, “but Mikaela has been incredibly committed to doing that.” Stewart, meanwhile, said she hopes to continue to unlock more mysteries involving breast cancer.