Fox Chase Researchers Receive $1 Million Grant to Develop Platform That Could Assist in Development of New Drugs

John Karanicolas, PhD, co-leader of the Cancer Signaling and Microenvironment research program at Fox Chase Cancer Center, was recently awarded a $1 million grant from the W.M. Keck Foundation to develop a platform that could assist in the development of new drugs.

“Scientifically, the goal of this project is to design new compounds known as molecular glues,” said Karanicolas. Molecular glues are small molecules that bind to the surface of a target protein and change its shape, allowing it to engage with a different set of protein partners than its usual repertoire.

“This is important because in many cases proteins act on their signaling partners through proximity, so simply bringing two proteins close to one another can, in some special cases, be enough to activate the signaling pathway,” said Karanicolas. “This idea of molecular glues can be used to enhance existing signaling pathways or to rewire cellular signaling pathways in a way that may allow us to reach what were previously ‘undruggable’ targets,” meaning ones that do not respond to existing drugs.

Karanicolas’ project is one of 11 medical research grants totaling $12.8 million selected for funding by the Keck Foundation’s Board of Directors in 2022. The foundation funds new and innovative projects that they believe have the potential to be transformative and far-reaching.

“The high regard for the role of basic science within our institution, along with our culture of collaboration and collegiality, helps make awards like this possible,” said Jonathan Chernoff, MD, PhD, Cancer Center Director at Fox Chase. “This grant is not only an acknowledgement of our talented scientists, but also a distinction that reflects well on our entire institution.”

Karanicolas’ project, “Using Deep Learning to Enable Rational Design of Molecular Glues,” aims to develop machine learning tools for identifying compounds that stabilize select protein interactions. Machine learning is a process by which computers are taught how to learn and perform certain functions. He and a team of five other Fox Chase investigators will then test in cancer cells whether the compounds designed on the computer induce association of the selected target proteins.

He added that, if successful, the studies will provide a necessary shift away from techniques that simply hope to find molecular glues by serendipity and move instead towards rational design methods that will enable much broader applications.

“What’s tremendous about the Keck Foundation is that they’re funding the project in a very holistic way because of their forward-thinking focus. The grant mechanism is unique in that it’s really supporting the overarching conceptual goal of the project and allows us to defer for later the specific applications,” said Karanicolas. “I’m very excited that this grant is supporting us in doing these truly cutting-edge fundamental studies, since these will open the door to countless new applications.”

The W. M. Keck Foundation was established in 1954 in Los Angeles by William Myron Keck, founder of The Superior Oil Company. One of the nation’s largest philanthropic organizations, the W. M. Keck Foundation supports outstanding science, engineering, and medical research. The Foundation also supports undergraduate education and maintains a program within Southern California to support arts and culture, education, health, and community service projects.

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Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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