The E3 ligase adaptor cereblon is a target of thalidomide and lenalidomide, therapeutic agents that are used in the treatment of hematopoietic cancers despite teratogenic toxicity. Despite the expanding use of cereblon in targeted protein degradation technologies, identification of the recognition domain that controls the endogenous substrate selection mechanisms of cereblon, has remained elusive.

At the 2022 International Symposium on Chemical biology, Prof. Christina Woo will describe chemoproteomics approaches to target identification in the study of molecular glues like lenalidomide, and how these chemical biology approaches can reveal new insights about the thalidomide binding domain of cereblon.

 

 

The final layer of biological regulation is through a network of molecular signals relayed by chemical modifications on proteins, which influence how proteins interact with each other and function. Reading and (re)writing the code relayed by these chemical modifications requires new innovations to systematically discover and measure where, when and how they occur, their regulatory outcomes, and the development of new cellular approaches to edit these modifications on target proteins. The overarching goal of the Woo lab is to understand how these small molecules influence protein function and biological signalling using chemical biology and proteomics approaches.

To decrypt the code, the Woo lab uses a range of different backgrounds (chemical biology, molecular biology, organic chemistry, proteomics, and data analysis) which allows them to study complex projects. One of them is focused on trying to understand the natural mechanism of E3 ligases, which are a key player for protein degradation by selecting which proteins get ubiquitylated. It has been shown that small molecule ligands can adapt ubiquitin ligases and chemically induce degradation of new target proteins. However, in many cases, the natural mechanisms of E3 ligases are unknown, which makes the discovery of new chemical adapters challenging. The Woo groups has been studying these E3 ligases using chemoproteomic techniques and developing new ligands as probes for biological inquiry and strategies for therapeutic intervention.

During her talk “Chemical biology studies of the thalidomide binding domain of cereblon” at the 2022 International Symposium on Chemical Biology, Prof. Woo will describe chemoproteomics approaches to target identification in the study of molecular glues like lenalidomide, and how these chemical biology approaches can reveal new insights about the thalidomide binding domain of cereblon.

 

More about Christina M. Woo

Christina M. Woo is an Associate Professor in the Department of Chemistry and Chemical Biology at Harvard University, and an affiliate member of the Broad Institute. She obtained a BA in Chemistry from Wellesley College (2008), and conducted undergraduate research in the laboratory of Professor Dora Carrico-Moniz. She obtained her PhD in 2013 from Yale University under the guidance of Professor Seth B. Herzon as an NSF predoctoral fellow in the synthetic and chemical biology studies of diazofluorene antitumor antibiotics. In 2013, Christina joined the laboratory of Professor Carolyn R. Bertozzi at the University of California Berkeley as a Jane Coffins Child postdoctoral fellow, and continued at Stanford University (2015) as a Burroughs Wellcome Fund postdoctoral fellow, where she developed a mass-independent chemical glycoproteomics platform for the identification of non-templated post-translational modifications. Christina joined the faculty at Harvard University in 2016.

Christina’s independent research focuses on how small molecules influence protein function and biological signalling using large-scale chemical biology approaches. Her research has been recognized by the Camille-Dreyfus Teacher-Scholar Award, Sloan Research Foundation, NSF CAREER, Bayer Early Excellence in Science Award, the NIH DP1 Avenir Award, and the Ono Pharma Foundation Breakthrough Science Award.

In 2020, she earned national recognition with the title Camille-Dreyfus Teacher-Scholar, an honor given to young chemists who excel in the lab and classroom.

 

To go further

• “Mapping the Small Molecule Interactome by Mass Spectrometry”, Biochemistry, 2018.
• “Development of Photolenalidomide for Cellular Target Identification”, JACS, 2022.
• This 2020 interview highlights her commitment to undergraduate education.