Speaker:Umut Şahin
Title: SUMOylation in health and disease and its potential for targeted therapies
Date/Time: October 16, 2023 1:40 P.M.
Place: FENS G032
The seminar will be held in person, however there will also be an option to attend online using the link below:
https://sabanciuniv.zoom.us/j/7260077994
Abstract: My lab studies the biology of SUMO (Small ubiquitin-like modifier) proteins, their role in pathogenesis, and their potential as drug targets. SUMOylation is an evolutionarily conserved post-translational protein modification essential for normal cell function and is disrupted in multiple disease states, including cancer, neurodegeneration, and infectious diseases. We conduct curiosity-driven fundamental research to dissect the functions of SUMOylation in vital cellular processes, disease biology, drug discovery and genome engineering.
I will present our work demonstrating the role of SUMOylation on the efficacy of the popular CRISPR/Cas9-based genome editing technology with important implications in gene therapy. We have recently reported on our discovery of Cas9 SUMOylation, the first post-translational modification to be described on this important bacterial enzyme. We found that K848, a key residue in the HNH nuclease domain which directly interacts with the target DNA is modified by SUMO, modulating Cas9’s RNA-guided DNA binding efficacy. Our results shed light on the regulatory mechanisms controlling Cas9 behavior in human cells and provide an opportunity to establish a more precisely controlled gene editing platform in the lab and the clinic.
My group is particularly interested in understanding the cellular mechanisms leading to neurodegeneration in ALS (Amyotrophic Lateral Sclerosis), a neurodegenerative disease that represents a critical unmet medical need. We use multidisciplinary approaches including biochemistry, biophysics, proteomics, genetics and transgenic mouse models to explore the potential of SUMOylation as a target process that can be manipulated with therapeutic benefits in ALS. Here, I will discuss our recent efforts to develop and validate a SUMO modulating targeted therapy that can now diminish disease incidence, alleviate symptoms and extend lifespan in a preclinical model of ALS. Our results demonstrate the feasibility of SUMO-mediated protein degradation as a druggable node to treat neurodegenerative diseases and could have direct consequence in patient care.
Bio:Umut Şahin is an associate professor of Molecular Biology and Genetics at Boğaziçi University. He leads a dynamic team conducting cutting-edge research to study the functions of SUMOylation in health and disease processes. His research group takes a multidisciplinary approach to tackle complex problems and integrates basic science with translational medicine.
After making significant contributions to the field of EGFR (epidermal growth factor receptor) signaling during his Ph.D. training with Prof. Carl Blobel (MD, Ph.D.) at Memorial Sloan-Kettering Cancer Center in New York, he joined the laboratory of Prof. Hugues de Thé (MD, Ph.D., College de France, Paris) where he played a key role in elucidating the biochemical functions of PML nuclear bodies and defined these membraneless organelles as cellular hubs for protein SUMOylation.
Umut Şahin was trained as a cell biologist, biochemist and a cancer biologist, and has published numerous research and review articles in high-profile journals (Journal of Cell Biology, Blood, Nature Communications, FEBS Journal, Life Science Alliance, Journal of Pathology, etc), received multiple awards and grants (EMBO Installation Grant, BAGEP, TUBITAK-France Bilateral Grant Program, TUBITAK 2247A National Leader Researchers Program) and established collaborations with local and international groups in academia and biopharma (IPSEN, Gilead, BrainEver).