NSF CAREER Award to support cancer research of CBE alumnus Shreyas Rao

Metastatic breast cancer cells lodging in the brain may rest in sleep mode before awakening to wreak havoc, but the reasons why the cells stay dormant and later become active is not fully understood.

With the support of a five-year, $514,890 CAREER Award from the National Science Foundation, a pioneering bioengineering project at The University of Alabama will engineer environments that mimic conditions in the brain to gain insight into this process in metastatic breast cancer.

“Not much is known about how these cells can stay dormant in the brain and wake up at a later time and result in recurrence,” said CBE alumnus Shreyas S. Rao, Reichhold-Shumaker Assistant Professor of chemical and biological engineering at the University of Alabama. “If we understand the mechanisms, then we can potentially develop therapeutic approaches that essentially target these cells.”

There is no cure for metastatic breast cancer, or stage IV breast cancer. The five-year relative survival rate for patients is about 22 percent, according to the American Cancer Society.

Metastatic breast cancer cells travel primarily to the lungs, liver, bones or the brain, but each organ offers these cells a different environment, meaning understanding the process in one organ does not translate to another.

For the study, Rao and his students are developing a 3-D experimental model of dormancy in brain metastatic breast cancer cells using hydrogels that can mimic certain aspects of the brain tissue. These hydrogels are created using hyaluronic acid, a major component of the brain environment, and will allow the team to test whether biophysical, biochemical and cellular cues in the brain environment regulate the dormancy of breast cancer cells that have metastasized to the brain. Rao chose to focus on brain tissue for the study because it is the least-understood of the organs that can house dormant cancer cells.

“The environment in the brain plays a key role in influencing whether or not the cancer cells will stay in a dormant state,” Rao said. 

Rao and his students will engineer brain tissue-mimicking environments incorporating signals they believe may play a role in cancer dormancy such as stiffness of the tissue, the presence of certain biomolecules and native cells in the brain.

“We want to find out what combinations of signals keep the cells dormant and also wake them up as well as understand the underlying mechanisms of why this switch happens,” he said. "If we can understand the key mechanisms that are driving the process, we have a better chance of manipulating those elements with the goal of improving patient survival rates," he said.

The National Science Foundation's Faculty Early Career Development, or CAREER, Program is a Foundation-wide activity that offers the NSF’s most prestigious awards in support of early-career faculty who have the potential to serve as academic role models in research and education and to lead advances in the mission of their department or organization. As part of the outreach mission of NSF, the NSF CAREER grant also covers an educational component. Professor Rao's award will enable four cohorts of six high school students and three high school teachers from the state’s economically challenged Black Belt region to learn and work in Rao’s lab for four days during the summer over the course of the grant.

Professor Rao obtained his MS and PhD degrees in chemical engineering from The Ohio State University in 2010 and 2012, working in the laboratory of Professor Jessica Winter. Rao became interested in the bioengineering side of chemical engineering while still a chemical engineering student in India, and came to Ohio State after following Professor Winter's research. He completed his post-doctoral studies at Northwestern University and the University of Michigan with Professor Lonnie Shea, working on developing an early detection platform for metastatic disease.

Shreyas joined the University of Alabama in August 2015 and was named Reichhold-Shumaker Assistant Professor in 2017.

-Based on a story by Adam Jones, UA communications