Rongsheng (Ross) Wang, assistant professor of chemistry, has been awarded a five-year, $1.95 million grant from the National Institutes of Health to develop an innovative approach to chemically label proteins of interest—a strategy that could lead to advances in the diagnosis and treatment of cancer, inflammatory and neurogenerative diseases.

Wang’s focus is on what are called post-translational modifications (PTMs) of proteins, primarily caused by enzymes after proteins first form. The PTMs modify proteins with additional chemical functional groups that can alter the function of the proteins and, thus, activities in cells.

“PTMs have recently emerged as a class of important biological pathways that have been reported as a key to certain human diseases such as cancer, inflammatory disorders and neurogenerative diseases,” says Wang. “Yet it has been hard to specifically identify such substrate proteins of PTMs.”

The current tools to label PTM substrates are limited, says Wang, because they can actually create unwanted effects in the molecules under study, especially within a live cell environment.

Wang is proposing a new, multi-step process that avoids such effects, including interference with cellular signaling. It uses the chemical fluorine to more accurately and completely label PTM-related proteins. His objectives include: (1) developing a technique to tag protein substrates of the PTMs in live cells, with the chemical fluorine; (2) using this fluorine-tagging strategy to study the PTM substrates that are potentially important to the survival of cancer cells, but not regular cells; and (3) investigating PTM substrates that, in the thymus gland, control the activation of T cells—which play a pivotal role in the body’s immune responses. 

“Our ultimate goal is to invent in vivo chemical labeling methods that efficiently and accurately identifies disease-associated subcellular components,” says Wang, who is also a primary member associated with research at the Fox Chase Cancer Center.  “It could lead to the identification of previously unknown proteins that could be key players in controlling disease pathways. This would greatly accelerate disease diagnosis and treatment, and result in a tool box of PTM probes that the entire scientific community could use.”

The Maximizing Investigators Research Award (MIRA) awarded to Wang by the National Institute of General Medicine runs through 2024.