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Grant spurs research into how cancer cells spread

Mar. 3, 2016, 9:01 AM

Aron Parekh, Ph.D., assistant professor of Otolaryngology, has received a four-year, $790,000 Research Scholar Grant from the American Cancer Society to further his research into the mechanical and biological properties of cancer cells and the methods by which they leave the initial tumor and spread or metastasize to other parts of the body.

Aron Parekh, Ph.D.

“I am honored to receive this important grant, which will help us explore the biomechanical complexities of cancer cell invasion,” Parekh said.

Patient survival is more problematic if cancer cells invade surrounding tissue or metastasize in another part of the body.

Parekh said the response of cancer cells to tissue stiffness or rigidity in the tumor microenvironment plays a crucial role in driving these cells to leave the primary tumor site. He has been studying a molecule called Rho-associated kinase (ROCK), which regulates the force that cells exert to determine how stiff something is.

ROCK exists in two forms (ROCK1 and ROCK2), and Parekh and colleagues recently discovered that the two forms work in different ways.

To invade neighboring tissues, cancer cells must degrade the extracellular matrix (ECM) of these tissues.

“We want to understand how tumor rigidity regulates degradation through the forces that cancer cells use to sense how stiff the ECM is in both individual cancer cells and pairs of tumor cells. When we find cancer cells in pairs or triples and they’re touching, which means they’re interacting, there’s often more degradation under them.

“What we’re going to do then is measure forces between two tumor cells and see if the combined forces together make the cancer cells more invasive,” Parekh said.

His collaborator on this grant is Julie Sterling, Ph.D., assistant professor of Medicine in Clinical Pharmacology, Cancer Biology and Biomedical Engineering, who studies how cancer spreads to the bones. The two will use novel assays and methods that combine biology and engineering to understand the biochemical and biophysical mechanisms that regulate cancer cell activity, both in cell lines and animal models.

“Understanding these mechanisms will have a profound impact on the cancer invasion field since no ROCK therapies currently exist due to the diverse range of ROCK functions in cancer, presumably because of the distinct activities of these different ROCK forms which were previously thought to perform the same functions,” Parekh said.

Parekh earned his Bachelor of Science and Ph.D. in Chemical Engineering from Pennsylvania State University.

He served as a postdoctoral fellow in the Department of Pediatric Otolaryngology at the Children’s Hospital of Pittsburgh and as a postdoctoral scholar in the Department of Bioengineering at the University of Pittsburgh prior to joining the Department of Cancer Biology at VUMC as a research fellow. He joined the faculty in 2010.

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