ChemBio Seminar - Keriann Backus

The ChemBio Seminar Series presents: Keriann Backus

UCLA

Host: Michael Marty

Title: Chemoproteomic approaches to characterize electrophile- and redox-induced cellular stress 

Location: WEL 2.122

Refreshments served at 3:15pm

Cysteine is a unique amino acid, distinguished by its nucleophilicity and sensitivity to oxidative modifications. As a result of this privileged chemistry, cysteine-reactive molecules have emerged as high value tools for functional biology and drug development applications. Exemplifying the importance of these molecules, the recently FDA-approved drug Sotorasib functions by covalently modifying the Gly12Cys oncogenic form of KRAS, a protein long thought to be undruggable. Thus, there is widespread interest in the discovery of new ligandable (potentially druggable) and redox sensitive cysteine residues. Cysteine chemoproteomic platforms, including those from our group, are highly enabling technology to be increasingly used for the discovery of such high value cysteines. Our group recently revealed that stress granules, namely molecular condensates of RNA and proteins that form under cell stress, are induced by cysteine-reactive electrophilic druglike molecules (Nat Chem Bio, 2025). I will discuss our ongoing unpublished efforts using both cysteine and redox proteomic approaches to define the protein targets and molecular mechanisms driving this process and our efforts to establish best practices for cysteine chemoproteomics to ensure on target activity. I will also highlight our broader efforts to establish photocatalytic proximity labeling platforms and their application to defining the protein interactome.