Cyclic Peptides

After completing studies for the A.B., A.M., and Ph.D. degrees in chemistry at Harvard University, David W. Christianson joined the faculty of the University of Pennsylvania, where he is currently the Roy and Diana Vagelos Professor in Chemistry and Chemical Biology. At Penn, Christianson’s research focuses on the structural and chemical biology of the zinc-dependent histone deacetylases as well as enzymes of terpene biosynthesis. His research accomplishments have been recognized by several awards, including the Pfizer Award in Enzyme Chemistry and the Repligen Award in Chemistry of Biological Processes from the American Chemical Society, a Guggenheim Fellowship, and the Elizabeth S. and Richard M. Cashin Fellowship from the Radcliffe Institute for Advanced Study at Harvard University. Christianson is also a dedicated classroom teacher, and his accomplishments in this regard have been recognized by the Lindback Award for Distinguished Teaching at Penn and a Rhodes Trust Inspirational Educator Award from Oxford University. Christianson has also held visiting professorships in the Department of Biochemistry at Cambridge University and the Department of Chemistry and Chemical Biology at Harvard University. Christianson has served with Prof. Anna Pyle as Co-Editor-in-Chief of Methods in Enzymology since 2015.Parisa Hosseinzadeh's work integrates computational and experimental methods to design proteins and peptides, driven by the goal of making these tools accessible everyone. My scientific path began in Dr. Yi Lu’s lab, where I contributed to 19 publications on metalloprotein and enzyme engineering. Among my most notable achievements was redesigning 2V Azurin (Hosseinzadeh*, Marshall* et al., PNAS, 2015), modifying its active site across multiple variants and metals. Another highlight was co-authoring a Science paper (Mirts et al., 2018) with a mentee, underscoring my commitment to mentorship.Shortly before my postdoctoral work, I initiated an independent collaboration that led to my first solo publication (Journal of Molecular Biology, 2020). During my postdoc with David Baker, who received the 2024 Nobel Prize, I adopted computational protein design using tools like (Py)Rosetta, co-authoring five papers—three as co-first author. A key milestone was our 2017 Science publication (Hosseinzadeh*, Bhardwaj*, Mulligan* et al.), which demonstrated accurate cyclic peptide design and opened doors to widespread collaborations. It also introduced me to the Rosetta Commons, a network at the forefront of protein and peptide research.In my lab, we target fundamental and applied challenges in protein and peptide design, focusing on three main areas. First, we advance cyclic peptide design through both computational techniques and wet-lab validation, with multiple papers published and additional manuscripts forthcoming. Our efforts include designing inhibitors and activators for GPCRs and streamlining peptide design workflows. Second, we explore metalloproteins and enzymes, bridging established methodologies with new technologies to tackle structural and functional questions. These projects build on my PhD experience but employ an expanded toolkit, resulting in one published paper and several ongoing endeavors involving Type 1 copper proteins and novel enzymatic activities. Third, we engage in interdisciplinary collaborations on constrained peptides for diverse targets like BMP-2 and MMP-1, leading to published results and ongoing studies.Mentorship is integral to my approach: I measure success through both scholarly achievements and personal growth. I also promote science outreach via Pacific mentorship programs, STEM initiatives for women, and peer-mentorship networks. My perspective was profoundly reshaped 2 years ago by a stroke that caused partial vision loss and limited use of one hand. Sharing this experience in Nature (2024) reinforced my resolve to cultivate an inclusive scientific environment, where resilience and empathy drive innovation, collaboration, and meaningful progress.

• 1. To be determinedYu-Shan Lin2. Using NMR Spectroscopy to Study the Folding and Supramolecular Assembly of Conformationally Constrained β-Sheet PeptidesJames S. Nowick and Jason Zhu3. To be determinedAli Tavassoli4. Using AEP enzymes to cyclize cyclotides: ultrastable constrained peptidesDavid J. Craik5. Translational synthesis of constrained cyclic peptides using genetic code reprogramming”Toby Passioura6. To be determinedParisa Hosseinzadeh and Paris Watson7. To be determinedParisa Hosseinzadeh, Noora Azadvari and Ben Burress-Irving8. To be determinedBen Brown9. To be determinedScott Lokey10. Cyclic peptides as ligands for competition binding assaysJames Inglese11. To be determinedAlvaro Siano12. To be determinedGaurav Bhardwaj13. To be determinedVikram Khipple Mulligan14. To be determinedEugene Serebryany

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