Congratulations to the team on advancing a new therapeutic strategy for wild-type p53 cancers, which represent nearly 90% of pediatric and 50% of adult malignancies. TAPTAC1's unique design unites stapled peptide and PROTAC technologies to simultaneously target HDM2 and HDMX to maximize reactivation of the p53 pathway while diverting HMD2 from p53 to instead degrade BET proteins, resulting in potent and selective anti-cancer activity across liquid and solid tumor models. Special thanks to the Harrington Discovery Institute for their key financial and advisory support throughout the development of TAPTAC1, along with pivotal funding from the William Lawrence and Blanche Hughes Foundation to advance next-generation therapeutics for pediatric cancers.

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Congratulations to Cat Newman (MD-PhD graduate in Chemical Biology) and Micah Gygi (PhD Candidate in Biological and Biomedical Sciences) on the publication of their co-first authored paper in Cell, revealing a new layer of apoptotic regulation mediated by protein-protein and protein-membrane interactions between anti-apoptotic dimers and pro-apoptotic oligomers of the BCL-2 family. We are so grateful for the contributions to this work by the laboratories of Gerard Wong (UCLA), Thomas Wales (Northeastern University), Steven Gygi (Harvard Medical School), and Lixin Fan (NCI SAXS facility).

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Congratulations to Tommy DeAngelo and the lab team on uncovering how venetoclax-resistance mutations alter BCL-2 conformation—and how stapled BAD BH3 helices can overcome these structural barriers to BCL-2 blockade. Lead stapled peptides preserve and even enhance binding across clinical variants, including through compensatory interactions of the hydrocarbon staple itself. The insights provide a blueprint for designing next-generation BCL-2 inhibitors capable of overcoming venetoclax resistance.

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Congratulations to Sophia Tang and the entire collaborative team from the Walensky and Segal labs on the publication of a new strategy to tackle chemotherapy-induced peripheral neuropathy by targeting the IP3 receptor with a BCL-w BH4 mimetic.

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Congratulations to Matt McHenry on the publication of his PhD thesis research on the discovery of a small molecule covalent inhibitor of pro-apoptotic BAX, providing a blueprint for the development of therapeutics that can protect cells from premature or unwanted cell death.

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Loren Walensky is interviewed by Kerry Kavanaugh of Boston 25 News about the lab’s novel stapled lipopeptide inhibitors of SARS-CoV-2.

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Congratulations to Greg Bird and the entire collaborative team on advancing our stapled lipopeptide platform to combat highly pathogenic respiratory and hemorrhagic fever viruses of pandemic potential.

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Congratulations to Tito Adhikary on the publication of his PhD thesis research study that reports a noncanonical role for MCL-1 in the regulation of DNA integrity and cell cycle progression.

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