The Mark Foundation for Cancer Research is thrilled to welcome Daniel Nomura as the newest member of its Scientific Advisory Committee. Nomura, Professor of Chemical Biology at the University of California, Berkeley, director of the Novartis-Berkeley Center for Proteomics and Chemistry Technologies, and co-founder of Frontier Medicines, tackles one of the greatest challenges in drug development: targeting undruggable proteins.
Advances in genome sequencing and proteomics have allowed scientists to uncover substantially more details about proteins that go awry in disease. But such knowledge doesn’t always translate into therapeutic benefit because 85% of these potential drug targets lack easily accessible pockets, nooks, and crannies to which small molecule drugs can bind.
Through his research group at University of California, Berkeley, his academic collaborations with Novartis, and his start-up Frontier Medicines, Nomura is using chemo-proteomic approaches to reimagine drug design and develop entirely new therapeutic paradigms. He is taking a creative approach to drug design exploring strategies that use the cell’s own machinery to tag and destroy troublesome proteins. He and his team are also identifying novel small molecules and natural products that covalently interact with amino acid hot spots that change the biological function of proteins.
“These are not your classical drugs,” he says. “We had to come up with new therapeutic paradigms to manipulate protein function in a way that we couldn’t access before.”
Using advanced chemoproteomic technologies, Dan and his team have developed small molecules that directly target “undruggable” drivers of cancer. His lab has discovered many new molecules that recruit E3 ligases to tag protein targets with ubiquitin, which marks them for degradation and disposal, and even discovered a molecule that directly targets, chemically binds to, and inhibits c-MYC, a major transcriptional oncogenic driver of cancer that has been elusive to many other drug development efforts.
Nomura’s partnership with The Mark Foundation dates back to 2018, when he received his first ASPIRE Award to discover new binding sites, or “hotspots”, on cancer-relevant protein targets, as well as covalent small molecule ligands that bind those sites. He was granted a Phase II ASPIRE Award in 2019 to continue that work as well as to develop new approaches that use small molecules to induce the proximity and interaction of proteins that would typically not come together in the cell, resulting in new functions that are therapeutically beneficial.
“With Mark Foundation funding, we have been able to expand upon completely new therapeutic paradigms based in chemical biology,” he said.
In January of 2020, Dan worked with The Mark Foundation to host an intensive workshop focused on chemically induced proximity, convening leaders in the field to catalyze new ideas and spark collaborations. “The field is exploding right now,” he said. Starting this month, he looks forward to bringing his vision to the Scientific Advisory Committee and hopes to build on the Mark Foundation’s history of supporting “fun, creative and cutting-edge research in cancer.”
“I’m really excited about helping the Mark Foundation fuel the next generation of innovative cancer research and invest in the most promising companies,” he says.