Cleveland Clinic Physician Earns Two Prestigious Young Investigator Awards

Cleveland Clinic urologic oncologist and researcher Byron Lee, MD, PhD, has received two significant awards recognizing his research in chromatin modifier genes and bladder cancer: a Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research and a Young Investigator Award from the Bladder Cancer Advocacy Network (BCAN).

Dr. Lee’s research focuses on understanding how chromatin modifier gene alterations contribute to the development of bladder cancer, its progression and its response to therapy. He has a primary appointment in the Glickman Urological and Kidney Institute Department of Urology and a secondary appointment in the Lerner Research Institute Department of Cellular and Molecular Medicine.

“Kimmel Scholar Awards have been crucial in supporting young investigators branching out into new areas of cancer research to advance our understanding of the disease and develop novel therapies. It’s a great honor to be a Kimmel Scholar,” says Dr. Lee. Kimmel Awards support early career research scientists and physicians with a two-year $200,000 grant.

The BCAN Young Investigator Award, a one-year $50,000 grant, specifically encourages early career researchers to pursue bladder cancer investigations to improve patient outcomes.

“This award not only provides funding, but also the opportunity to share my work and form lasting collaborations within the bladder cancer community,” Dr. Lee says.

“Dr. Lee has already proven to be a superb addition to our urologic team,” says Edmund S. Sabanegh Jr., MD, Chairman, Department of Urology. “With his unwavering focus on the role that genetics plays in bladder cancer, Dr. Lee’s work will significantly improve our understanding of this complex disease and holds great promise in ultimately improving the outcomes for patients who contract this all-too-common cancer. We have high expectations for Dr. Lee’s continued contributions to the field, and are very proud of him for this recent recognition.”

Pursuing genetic understanding of bladder cancer

For two decades, little progress was made in developing new treatments for bladder cancer, the fifth most common cancer diagnosed in the United States, due to lack of public awareness and financial support for bladder cancer research, Dr. Lee notes. Recently, genomewide analyses by organizations such as The Cancer Genome Atlas yielded a major new discovery: the vast majority of urothelial bladder cancers harbor a chromatin modifier gene mutation. Some chromatin modifier mutations were identified in both nonmuscle-invasive and muscle-invasive disease, which suggests that they occur early in the disease process and can heavily influence cancer biology. This has become the focus of Dr. Lee’s work.

Chromatin modifiers control how DNA is organized inside a cell’s nucleus, playing a central role in the regulation of proper gene expression, initiation of DNA replication, and recombination, Dr. Lee explains. Mutations in these genes can substantially alter a cell’s behavior and lead to malignancy. They have also been found in a wide variety of malignancies, including cancers of the lung, kidney, colon, ovary and white blood cells.

The functional consequences of chromatin modifier mutations in bladder cancer are not fully understood. Dr. Lee and others at Cleveland Clinic are focusing on how these mutations promote urothelial cancers of the bladder and upper urinary tract and ways to target these mutations through new drug combinations.

Cleveland Clinic was one of 14 centers that participated in a phase 2 clinical trial evaluating the epigenetic drug mocetinostat in bladder cancer. “The results will help us understand the clinicopathologic and molecular factors that affect the tumor’s response to the drug,” Dr. Lee adds.

Dr. Lee’s team is using the gene editing technology, CRISPR, to delete chromatin modifier genes in early bladder cancer and study how that affects cell behavior.

“Much of our work wouldn’t be possible without the additional funding; it speeds up the process and points us in the right research direction,” he says.