Research Information
Research Interests
Dr. Cao’s scientific dream is that, given any therapeutic target, we can develop a rational drug discovery strategy that reliably leads to life-saving medicines.
Approximately 80% of human proteins remain undruggable because they lack ligand-binding pockets. Exemplified by cancer drugs lenalidomide and pomalidomide, molecular glue degraders are an emerging class of transformative small-molecule therapeutics that can induce the selective degradation of these previously undruggable proteins. The Cao laboratory is dedicated to transforming molecular glue discovery from rare, serendipitous events into a rational and predictable process. We integrate experimental and computational approaches to establish the fundamental principles governing molecular glue function, translate these principles into a framework for rational drug discovery, identify and advance preclinical candidates, and partner with pharmaceutical companies to deliver new medicines that expand therapeutic options for patients. Our vision is to establish molecular glue discovery as a rational, scalable, and predictive paradigm that makes the undruggable druggable and expands therapeutic opportunities for patients with cancer and other diseases.
Lab Values
Integrity • Creativity • Collaboration
Educational & Training Background
Dr. Cao received his Ph.D. in Microbiology and Cell Science from the University of Florida under the mentorship of Dr. Julie Maupin-Furlow. Inspired by the urgent need for new therapies following the loss of his uncle to pancreatic cancer, he pursued postdoctoral training in Dr. Ning Zheng's laboratory at the Howard Hughes Medical Institute, University of Washington. There, through chemical biology, structural biology, and quantitative biophysics, he elucidated the molecular mechanisms of molecular glues with multiple high-impact publications and led a pancreatic cancer drug discovery program targeting KRAS. This experience reinforced his commitment to bridging fundamental discovery with therapeutic development and laid the foundation for his independent research program.
Selected Publications
Cao S, Kang S, Mao H, Yao J, Gu L, Zheng N. (2022). Defining molecular glues with a dual-nanobody cannabidiol sensor. Nature Communications 13(1): 815.
Cao S*, Garcia SF*, Shi H*, James EI, Kito Y, Shi H, Mao H, Kaisari S, Rona G, Deng S, Goldberg HV, Ponce J, Ueberheide B, Lignitto L, Guttman M, Pagano M, Zheng N. (2024). Recognition of BACH1 quaternary structure degrons by two F-box proteins under oxidative stress. Cell 187(26): 7568–7584.e22.
Cao S. (2024). Lessons from natural molecular glue degraders. Biochemical Society Transactions 52(3): 1191–1197.
Zhao Z*, Xu W*, Feng EY*, Cao S*, Hermoso-López A, Peña-Vega P, Lloyd HC, Porter AKD, Guzmán M, Zheng N, Woo CM. (2026). PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates. Nature Chemical Biology 22: 802–812.
Shi H, Wang X, Yu C, Mao H, Jiao F, Braitbard M, Shor B, Zhang Z, Hinds TR, Cao S, Fan E, Schneidman-Duhovny D, Huang L, Zheng N. (2026). CSN5i-3 is an orthosteric molecular glue inhibitor of COP9 signalosome. Nature 652: 1375–1383.
Google Scholar: https://scholar.google.com/citations?user=FQ78bCQAAAAJ&hl=en&oi=ao