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The Laboratory of Post-Translational Modifications


 Learn More  Meet the Team




Umut Şahin

____________
member,
EMBO Young Investigator Program
Gilead* Fellowship Program 
The Science Academy, Young Scientist Program
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I am an assistant professor in molecular biology & genetics @ Boğaziçi University,  the Center for Life Sciences and Technologies. I manage the Laboratory of Post-Translational Modifications, a biomedical research laboratory supported by the European Molecular Biology Organization (EMBO) and Gilead Sciences, Inc.*

My work is centered around the small ubiquitin-like modifier (SUMO) conjugation system. We are interested in how this pathway regulates essential biological processes and contributes to disease. We engage in translational research & experimental therapeutics, and investigate how genetic and pharmacologic manipulation of the SUMO system may be beneficial in clinical settings.

I received a PhD degree in Molecular Biology & Biochemistry from Brown University with dissertation performed at Sloan-Kettering Institute and Cornell Medical School with Carl Blobel. My thesis work focused on post-translational proteolytic activation of EGF receptor ligands and resulted in a seminal paper in the Journal of Cell Biology, now a citation classic.

I then moved to Pasteur Institute in Paris where I spent several years working in Pascale Cossart s department. For the past 6 years, I was a post-doc with Hugues de Thé ( College de France). Together with Valérie Lallemand-Breitenbach, Hugues and I uncovered the long-sought biochemical function of PML nuclear bodies as cellular machineries of protein sumoylation and destruction. Click here to read the implications of our discovery.

* Gilead Sciences is listed, along with Apple, Google, Microsoft, Amazon and Tesla, among the World’s most innovative companies.

RESEARCH


My group studies the basic science and medical aspects of a vital eukaryotic process called sumoylation, and of the tightly-linked PML protein, a prominent tumor suppressor.


1) Small Ubiquitin-like Modifiers


Sumoylation is a post-translational protein modification essential for life, which involves covalent conjugation of target proteins with the SUMO (small ubiquitin-like modifier) peptide. This may alter target function, enzymatic activity, subcellular localization and stability. Sumoylation also regulates macromolecular interactions, aggregation and solubility. One of the major interests of my group is to explore potential implications of the latter for the pathogenesis and management of neurodegenerative diseases. An unexpected consequence of sumoylation has recently emerged: sumoylation of a target may also trigger its ubiquitination and destruction by the proteasome.




2) Nuclear Organization & PML Nuclear Bodies


Aside from harboring a vast amount of genetic material, the eukaryotic nucleus is highly organized into distinct microenvironments such as PML nuclear bodies. This organization is often compromised in cancer and viral diseases. For example, in acute promyelocytic leukemia (APL), an aggressive subtype of myeloid leukemias, PML nuclear bodies are disrupted. A combination of two potent drugs - arsenic & retinoic acid - can enforce reformation of PML nuclear bodies and cure APL. The scaffold of PML nuclear bodies is the PML (promyelocytic leukemia) protein.




In APL a genetic defect create a fusion oncogene: PML/RARA. The latter impairs the function of PML protein and disrupts PML nuclear bodies. PML nuclear bodies recruit numerous partner proteins, including transcription factors (i.e. P53, Rb) and DNA repair proteins. As a post-doc in Hugues de Thé’s lab, I have recently identified the long-sought biochemical function of PML nuclear bodies as catalytic drivers of partner protein sumoylation and/or ubiquitination & degradation. We have demonstrated that some toxic proteins can be pharmacologically forced and channelled into this “PML/SUMO/Ubiquitin-mediated degradation” system (i.e. HTLV1 Tax oncoprotein) with a clear clinical benefit in leukemia patients.






TEAM


Overview

We are part of the Center for Life Sciences & Technologies in Istanbul, a novel, innovative research center comprising faculty from a dozen disciplines ranging from chemistry to computer science. We employ biochemical, biophysical, genetic, computational and in vivo techniques and collaborate with leading scientists and medical doctors within the country and abroad.

Our EMBO YIP mentors:

1. Prof. Anne Bertolotti @ University of Cambridge, UK
2. Prof. Hugues de Thé @ College de France, Paris
3. Dr. Gerlind Wallon, EMBO Deputy Director


Members



Group Leader


Umut Şahin, PhD
Full CV

Principle Investigator
____________

member,
EMBO Young Investigator Program
Gilead Fellowship Program
The Science Academy , Young Scientist Program
____________

Doctoral work with Prof. Carl Blobel at Memorial Sloan-Kettering Cancer Center & Weill
Medical College of Cornell University, New York, USA

Post-doctoral work with Prof. Hugues de Thé at INSERM & College de France, Paris, FR






Arda Baran Çelen


Graduate Student
B.Sc. Florida State University

Prior to joining the lab, Arda worked as an intern in Carl Blobel’s lab at Hospital for Special Surgery in New York.





Bahriye Erkaya


Graduate Student
M.Sc. Koc University
B.Sc. Bilkent University


Bahriye also studied at University of California, Los Angeles as an exchange student. She had an internship at Cedars Sinai Hospital under the supervision of W.K. Chung, PhD and Bekir Cinar, PhD. and worked in Dr. Ilknur Ay s Lab at Harvard Medical School.





Duygu Yeşildağ


Graduate Student
B.Sc. Istanbul Technical University





Harun Öztürk


Graduate Student
B.Sc. Istanbul University

Summer Internship at TUBITAK MAM in enzyme and microorganism molecular genetics laboratory





Sezgi Canaslan


Graduate Student

Prior to joining tha lab, Sezgi worked in Prof. Georg Halder's lab at KU Leuven VIB Center, Belgium





Yusuf Tunahan Abacı


Graduate Student.
B.Sc. Istanbul Technical University

Prior to joining the lab, Yusuf worked as a research technician in Darwin Berg's lab at the University of California, San Diego




FUNDING


Our research is supported and funded by the European Molecular Biology Organization, Gilead Sciences, Inc., and the Science Academy of Turkey.


Cinque Terre
Cinque Terre
Cinque Terre



PUBLICATIONS


Full list on PubMed or Google Scholar

  • Adult T-cell lymphoma response to arsenic/interferon therapy is triggered by SUMO/PML/RNF4-dependent Tax degradation (2015) Blood. Sahin U/Dassouki Z et al.

  • Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication (2014) Nat Commun. Sahin U et al.

  • Oxidative stress-induced assembly of PML nuclear bodies controls sumoylation of partner proteins (2014) J Cell Biol. Sahin U et al.

  • PML nuclear bodies: assembly and oxidative-stress sensitive sumoylation (2014) Nucleus. Sahin U et al.

  • PML nuclear bodies: regulation, function and therapeutic perspectives (2014) J Pathol. Sahin U et al.


  • CONTACT


    Boğaziçi University

    Department of Molecular Biology & Genetics
    Center for Life Sciences & Technologies
    Istanbul, TR

    Phones: +90 212 359 66 27
    Fax: +90 212 287 24 68

    E-Mail: umut.sahin@boun.edu.tr