VCU news

By Sarah Murphy

Picture this: You see a crowd of people, all moving in the same direction. Maybe they’re heading into a sports arena or boarding a subway train.

Everyone in the crowd is a little different — in appearance, yes, but also in how they act and react to the people around them. Each is an individual, communicating differently from one another and responding to the surroundings differently. Some move to the front, leading the crowd to a certain destination, while others fall into follower positions.

How do the leaders communicate to the followers? How will different types of followers respond differently to the leaders guiding the way?

These are some of the questions guiding the research of Priscilla Hwang, Ph.D., assistant professor in the Department of Biomedical Engineering in Virginia Commonwealth University’s College of Engineering. But instead of crowds of people, she is examining crowds of cancer cells.

Hwang is studying the microenvironments cancer cells live in and their migration to different parts of the body — also known as cancer metastasis. She began studying the topic in her postdoctoral research and has continued to explore it from different angles.

Currently, Hwang is partnering with principal investigators Gregory Longmore, M.D., and Amit Pathak, Ph.D., of Washington University in St. Louis on a new phase of research fueled by a grant from the National Cancer Institute.

Aside from skin cancer, breast cancer is the most common cancer in women in the United States, according to the American Cancer Society. The primary cause of breast cancer mortality is tumor metastasis, making Hwang’s research significant.

“Once a cancer has metastasized, it’s probably going to respond differently to therapies that are not specific for migration. That may be part of the reason why therapies are not as effective toward metastatic breast cancer,” she said. “If we can understand the pathways of the events that are happening during metastasis, that may help us design targeted therapies that are going to treat this more effectively.”

The five-year NCI grant was awarded in spring 2022, and funding began in August 2022.

“This grant is really exciting because our previous work, which was published in Cancer Research and Developmental Cell, is the foundation by which this new grant is built upon,” Hwang said. “Receiving this grant shows how energized the community is about the direction our work is headed.”

Understanding cancer migration

When metastasis occurs, it often means a group of cancer cells is moving. When groups of cells are moving, there are many different types of cells that can be embodied in these clusters — just like in the crowd of people. Hwang and her partners’ research combines biomedical and mechanical engineering with molecular biology in hopes of developing a comprehensive understanding of how and why groups of cancer cells move together.

Early in their research, Hwang and the team designed a “cancer-on-a-chip model,” a microfluidic model of breast cancer. They borrow electrical engineering concepts for the construction. First, the researchers draw out their blueprint and etch it on a silicon wafer in order to make a master mold. They can then take a silicon material to make a copy, or an inverse stamp, of the print. They then insert breast cancer cells into this constructed environment and get different cells to move by adding different signals.

“From the first phase, we identified certain cells that can drive or initiate migration,” Hwang said. “Now, this new grant from the National Cancer Institute is focused on investigating what those actual pathways are that might be regulating the phenomenon that we’ve observed.”

When there are clusters of tumor cells moving together, there are many different types of cells wrapped up in the cluster, such as stromal helper cells or immune cells. Hwang and her colleagues want to understand how different signaling pathways in the various cells within the moving cluster work separately or together to contribute to metastasis.

“We believe that by understanding these reactions and relationships, we’ll have a better idea of what therapies might be more effective at targeting metastatic disease,” Hwang said.

Through the NCI grant, Hwang, Pathak and Longmore have been able to fund graduate students working in the lab. The first started during the fall 2022 semester, helping Hwang with experiments and making the microfluidic platforms. There is also a group of students and faculty working on the Washington University side of the partnership.

In 2022, Hwang received a prestigious Faculty Early Development Award from the National Science Foundation; the award honors junior faculty who effectively integrate research and education. Read more about the complementary work of her research here.

For more information about VCU Biomedical Engineering, please visit the program website.