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Ashraf Brik

Professor

Technion-Israel Institute of Technology

Talk Information

Implications and Applications of PTMs

19 June 2025, 03:00pm - 03:30pm, in the Pacific Jewel Ballroom
L68 - AW – Ubiquitin Signaling: Chemistry, Biology and Drug Discovery

Ashraf Brik

Award Recipient

2025 Vincent du Vigneaud Award
The Vincent du Vigneaud Awards recognize outstanding achievement in peptide research at mid-career. The du Vigneaud Awards are sponsored by Bachem, and are awarded to two deserving recipients at the biennial American Peptide Symposia.


Biography


Professor Ashraf Brik is a distinguished chemist and chemical biologist, currently serving as a full professor at the Schulich Faculty of Chemistry at the Technion–Israel Institute of Technology. Renowned for his pioneering work in protein synthesis and post-translational modifications, he will be honored with the 2025 Vincent du Vigneaud Award at the American Peptide Society's 2025 Symposium, recognizing his significant contributions to peptide research at the mid-career level.

Academic Background

Born in Abu Snan, Israel, Professor Brik earned his bachelor's degree in chemistry from Ben-Gurion University of the Negev. He pursued his master's and doctoral studies at the Technion, with his Ph.D. research conducted jointly with The Scripps Research Institute under the mentorship of Professors Chi-Huey Wong and Ehud Keinan. His doctoral thesis focused on the design and synthesis of novel catalytic proteins based on polypeptide scaffolds. Following postdoctoral research, he joined the Department of Chemistry at Ben-Gurion University in 2007, where he was promoted to full professor in 2012. In 2014, he returned to the Technion, where he currently holds the Jordan and Irene Tark Chair in Chemistry.

Research Focus

Professor Brik's research centers on developing innovative chemical and semisynthetic methods for the site-specific synthesis of post-translationally modified proteins, such as ubiquitinated and phosphorylated proteins. His work has provided critical insights into the molecular mechanisms of ubiquitin signaling, which plays a pivotal role in various biological processes and diseases. By creating homogeneous protein conjugates, his lab facilitates structural, biochemical, and functional analyses that were previously challenging due to the heterogeneity of naturally modified proteins.

Notable Contributions

Among his significant achievements, Professor Brik's group was the first to chemically synthesize K48-linked tetraubiquitin chains, enabling detailed studies of ubiquitin-mediated processes. His research has led to the development of novel modulators targeting deubiquitinases, DUBs, enzymes implicated in cancer and neurodegenerative diseases. With over 200 publications and more than 11,000 citations, his work has been featured in prestigious journals, including Science, Nature Chemistry, and the Journal of the American Chemical Society.

Professional Engagements

Professor Brik is actively involved in the scientific community, serving on editorial boards of journals such as Cell Chemical Biology and ChemBioChem. He has received numerous accolades, including the Rappaport Prize for Excellence in Biomedical Research in 2024. His research is supported by various international funding agencies, including the European Research Council, ERC, the Israel Science Foundation, ISF, and the US-Israel Binational Science Foundation, BSF. Through his innovative research and leadership, Professor Brik continues to advance the field of chemical biology, contributing to the development of novel therapeutic strategies.


Talk Abstract


Ubiquitin Signaling: Chemistry, Biology and Drug Discovery

Ashraf Brik

Department of Chemistry, Technion – Israel Institute of Technology, Haifa, Israel

Posttranslational modification of proteins by ubiquitin, Ub, such as ubiquitination, mediates various cellular processes, including protein homeostasis, cell cycle, DNA repair, and viral infections. Understanding the role of ubiquitination in these events is the basis for unraveling its precise role in health and disease. Chemical protein synthesis offers great opportunities to dissect the molecular basis of Ub signaling, as demonstrated in various examples1.

In this talk, I will highlight the progress of my laboratory in preparing unique ubiquitin conjugates to advance our understanding of this signal in detail2. As a showcase, I will present the chemical synthesis of tetra-ubiquitinated proteins that are differentially labeled at the Ub chain and the protein of interest to shed light on fundamental aspects of proteasomal degradation3–5. I will also present the novel chemistry that emerged from these synthetic efforts and its utility in peptide and protein synthesis in general6,7.

Finally, I will show how these methods, combined with the Random Non-Standard Peptides Integrated Discovery method (RaPID), allowed us to discover novel cyclic peptides that modulate Lys48- or Lys63-linked Ub chains selectively to interfere with their biological function, for example, proteasomal degradation and DNA repair, and bring forward potential new therapeutic modalities8,9.

  1. Nature Chemistry, 2016, 8, 407–418.

  2. Journal of American Chemical Society, 2017, 139, 4971–4986.

  3. Nature Communications, 2021, 12:6173.

  4. Proc. Natl. Acad. Sci. 2013, 110, 17726-17731.

  5. Accounts of Chemical Research, 2019, 52, 12, 3361-3371.

  6. Angew. Chem. Int. Ed., 2017, 56, 10644-10655.

  7. Nature Communications, 2018, 9, 1-11.

  8. Nature Chemistry, 2019, 11, 644–652.

  9. Nature Communications, 2022, 13, 6174.