Assoc. Prof. Umut Şahin from Boğaziçi University is going to be at SABITALKS on February 22 at 14:00. The event will take place in person. You can attend the event in person in TTO (Technology Transfer Office) seminar room.
Location: Istanbul Medipol University Kavacık North Campus: https://goo.gl/maps/JDDjygVtFLWiPiMJA
*Participants from outside SABITA must fill in the participation form.
My lab is interested in studying the biology of SUMO (Small ubiqutin-like modifier) proteins, their role in pathogenesis, as well as their potential for the development of targeted therapies. SUMOylation is an essential post-translational protein modification, evolved to accomodate some of the complexities of eukaryotic cells and to regulate the intricate networks within these systems. Thousands of eukaryotic proteins are subject to and modified by SUMOylation, leading to changes in their structure, function, localization, stability or interactor profile. At the cellular level, SUMOylation is a key regulator of nuclear and genomic integrity, transcription, cell proliferation, stemness, senescence and infection, as well as of epigenetic and metabolic processes. At the physiological level, it acts as a crucial regulator of development. SUMOs’ participation in such an immense range of cellular mechanisms has informed our perspective on numerous pathological conditions, including cancer, neurodegeneration and infectious diseases.
We conduct curiosity-driven fundamental research to dissect the functions of SUMOylation in key cellular processes and pathogenesis, with a major interest in disease biology and drug discovery.
A growing number of bacterial and viral proteins have recently emerged as prime SUMOylation targets, highlighting the role of this modification during infection and innate immunity. My lab has recently focused on the biology of the CRISPR/Cas9 system, a popular genome-editing platform with potential to cure various genetic diseases. 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 stability and RNA-guided DNA binding efficacy. These results shed further light on the regulatory mechanisms controlling Cas9 behavior in human cells, which are important to resolve for safer clinical implementation of the CRISPR/Cas9 technology. We are currently investigating the implications of this discovery for Cas9 specificity and off-target activity, and also whether Cas9 SUMOylation is an evolutionarily conserved mechanism that is consequential for host-pathogen interactions.
My group is particularly interested in understanding the cellular mechanisms leading to neurodegeneration in ALS (Amyotrophic Lateral Sclerosis), with an ultimate goal to develop next generation therapeutics for the treatment of this disease. 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. Following years of in vitro and ex vivo work and in vivopreclinical studies, we have now managed to alleviate the disease-related motor function symptoms and to extend lifespan in an ALS mouse model receiving therapy. Our observations demonstrate the feasibility of SUMO-targeted protein degradation in ALS treatment and could have direct consequence in patient care.
Associate Professor
Department of Molecular Biology and Genetics
Boğaziçi University
Umut Şahin is an associate professor of Molecular Biology and Genetics at Boğaziçi University where he leads an active team that conducts cutting-edge research to study the functions of SUMOylation in health and disease processes. His main focus is proteolysis, the ubiqutin-proteasome system, ubiquitin-like proteins (i.e. SUMO), protein quality control mechanisms and the related pathologies. His research group uses multidisciplinary approaches to integrate basic science with translational medicine.
Following his graduation from Boğaziçi University, he conducted his PhD thesis research under the supervision of Prof. Carl Blobel (MD, PhD) at Memorial Sloan-Kettering Cancer Center (New York) which led to the discovery of the proteases that serve as the main activators of all ligands of the epidermal growth factor receptor (EGFR), which has crucial roles in development and cancer. During his post-doctoral training with Prof. Hugues de Thé (College de France, Paris), he studied the interplay between the cellular SUMO system and PML nuclear bodies, which are membraneless organelles tightly linked to acute promyelocytic leukemia, a rare and aggresive hematological cancer.
He has published numerous research and review articles in high profile journals (Journal of Cell Biology, Blood, Nature Communications, FEBS Journal, Life Science Alliance, etc), received multiple awards and grants (EMBO Installation Grant, BAGEP, TUBITAK-France Bosphorus Bilateral Grant Program, TUBITAK 2247A National Leader Researchers Program, research grants from Gilead, Inc., etc) and collaborated with both local and international groups in academia, as well as in pharmaceutical industry (IPSEN, BrainEver).