Degrading the mighty proteome with small molecules

Katherine Donovan’s research path hasn’t followed a linear trajectory; she’s zig-zagged from doing basic biochemical studies to proteomics-based translational research. In her words, she is now “designing small molecules to hijack the cell’s waste disposal system and redirect it to disease-causing proteins.”

Katherine Donovan

But Donovan’s movements have not been random, she said: “I’ve found that I gravitate toward collaborative interactions.”

During her Ph.D. at the University of Canterbury in New Zealand, Donovan studied the adaptive evolution of pyruvate kinases in E. coli. Using biochemistry and structural biology techniques, she demonstrated how mutations in the protein make the bacterium better able to tolerate low-glucose conditions.

After joining Eric Fischer’s lab at the Dana–Farber Cancer Institute in 2016, Donovan used proteomics to quantify changes in protein expression in mammalian cells when perturbed with drugs and small molecules. Her desire for collaboration motivated her to join Dana–Farber’s new Center for Protein Degradation, or CPD, in November 2018. There she built and managed the proteomics operation and developed novel technologies to advance drug discovery for different targets.

Now a lead scientist in the Fischer lab, Donovan spearheads multiple projects in proteomics as well as serving as a proteomics advisor to the CPD. Many of her projects are focused on finding degradation therapeutics for proteins involved in diseases such as cancer and Alzheimer’s.

Donovan’s favorite part about research is the community she gets to interact with daily. “People are the biggest driver in my job,” she said. “I am very lucky to have a fantastic proteomics team where everyone is super excited about science.”