“Welch’s new Catalyst for Discovery Program grant is so aptly named,” said Deepak Nijhawan, associate professor and distinguished chair in Biomedical Science at The University of Texas Southwestern Medical Center, “as it truly will be the catalyst for future discoveries. I am so excited to be one of the first recipients of the grant given how important Welch funding has long been to my research and to that of UT Southwestern.”
Over the past 10 years, working across disciplines and helped by technological advances, his team has built a platform that uses chemistry to evaluate small molecules as potentially useful drugs, discovering 10 potential candidates last year – lightning fast compared to traditional approaches.
With Welch’s Catalyst for Discovery grant, the team – including UT Southwestern collaborators Jef De Brabander, Joe Ready, Tian Qin, and their labs – plan to dramatically expand vital pharmaceutical development by exploring new chemistry and cell lines from diverse lineages as models of human physiology. They expect to discover dozens of new small molecule/protein pairs.
“The Welch Foundation has been absolutely essential to all the success we have had – both in my lab and across the biochemistry department at UT Southwestern overall,” Dr. Nijhawan said. “ And once again, with the Catalyst grant, Welch support will be transformational. The stage is set to do this even more rapidly – that’s where the Catalyst grant comes into play. It will help us leap ahead in our research and significantly accelerate the drug discovery pipeline.”
The project is focused on discovering small molecules with defined biological effects, uncovering principles of reactivity in cellular contexts, and developing tools for chemical biology.
“Many drugs are chemicals – small molecules – and we use chemistry to discover new biology,” Dr. Nijhawan said. “But small molecules are very challenging to work with and it has taken us decades to begin to understand how they affect biological systems.
Drawing upon the knowledge gained over the past decade’s work, the team will prioritize compounds that inhibit cell proliferation through interaction with single proteins. Then, using a novel forward genetics system and chemical strategies, they will locate their biological targets.
“Already we have seen our approach has taken us to surprising new places – we have discovered mechanisms that can affect proteins in previously unsuspected ways,” Dr. Nijhawan added. “Once we figure out how a molecule interacts with biological systems, it opens so many doors.”
The research also will identify small molecules to probe the biochemical pathways critical for cell viability. These tool compounds can be used to explore enzymology, metabolism, and proteomics, potentially revealing unexpected chemical reactivity inside active sites of proteins that highlight potential therapeutic opportunities.
“We have an amazing team here at UT Southwestern, bringing biology and chemistry together – it’s incredibly fun. And thanks to the Welch Foundation sharing our vision and providing support, there are so many exciting discoveries yet to come,” Dr. Nijhawan said.