Yifat Merbl, PhD, CRI Lloyd J. Old STAR, Tech Impact Award Weizmann Institute of Science Cellular proteasomes are considered the main compartment for protein degradation, and may be considered as the cellular ‘trash cans.’ Importantly, cellular proteasomes are key for antigen processing, cellular inflammation, and responsiveness to immunotherapy. Recently, Dr. Merbl developed state-of-the-art technology to examine the cellular ‘trash can’ in cancer. Much like detective work in which one can go through a person’s trash to learn about his/her lifestyle, inspecting degradation products provides invaluable insights into cellular function, which cannot be captured by snapshots of protein abundance alone. Using this approach, which Dr. Merbl calls proteasome profiling, she mapped the degradation landscape of tumor tissues and adjacent controls. She found distinct proteasome degradation patterns that were associated with the cancer phenotype and associated with lack of response to immunotherapy. Here, she intends to characterize the proteasome degradation landscape in melanoma, aiming to bring insight into mechanisms of immune evasion and lack of response to immunotherapy. Dr. Merbl’s approach should afford a novel paradigm by which proteasome degradation may be targeted in the context of precision oncology. As a CRI Lloyd J. Old STAR, Dr. Yifat Merbl explores the role of the protein destruction center cells, the proteasomes, in tumor immunogenicity and response to immunotherapy. Her research deciphers how different proteasome complexes influence tumor-host interactions and immune responses. By understanding proteasome biology, Dr. Merbl aims to develop novel precision oncology interventions to improve cancer treatment outcomes. Projects and Grants Modulating Tumor Degradation as a Novel Intervention in Cancer Immunotherapy Weizmann Institute of Science (Israel) | Melanoma | 2024 | CRI LLoyd J. Old STAR Mass spectrometry Analysis of Proteolytic Peptides – exploring the tumor degradome as a new front in precision oncology and immunotherapy Weizmann Institute of Science (Israel) | All Cancers | 2024 | Tech Impact Award Controlling proteasomal degradation for enhancing anti-tumor immunity Weizmann Institute of Science (Israel) | All Cancers | 2022 | CLIP Investigator
