Assoc. Prof. Dr. Umut ŞAHIN

The long term goal of our research is to understand the biology of SUMO proteins, to dissect their functions in health and pathology, and to explore their potential for targeted therapies. To this end, we use multidisciplinary approaches, ranging from cell biology to high resolution imaging, from proteomics to biochemistry, as well as transgenic animal models of disease.
Sumoylation is an essential post-translational protein modification evolved to accomodate the complexities of eukaryotic cells. Small ubiquitin-like modifier (SUMO) protein isoforms can be reversibly linked to lysine residues that reside within specific motifs on thousands of target substrates, leading to modulations in protein function, stability, solubility, localization, and interactor profile. Since its initial discovery 25 years ago, SUMO has been described as a key regulator of genomic stability, cell proliferation, epigenetics, stemness, and infection among other processes.

For more information, refer to our recent reviews:

• Sumoylation on its 25th anniversary: mechanisms, pathology, and emerging concepts
  (Celen and Sahin, 2020, FEBS Journal)
• Sumoylation in Physiology, Pathology and Therapy
  (Sahin, de Thé, Lallemand-Breitenbach, 2022, Cells)

A growing number of key proteins are emerging as prime sumoylation targets, and we aim to define how sumoylation regulates their function. We have recently discovered that the CRISPR-associated Cas9 enzyme was modified by both Ubiquitin and SUMO peptides. We found that modification by SUMO regulates both the stability and guide RNA-directed DNA-binding efficacy of the Cas9 enzyme. We are currently exploring the implications of these findings for genome editing technologies.

We are also exploring the potential of sumoylation for the development of targeted therapies. We recently reported a novel drug inducing SUMO-enforced androgen receptor destruction, causing loss-of-viability in prostate cancer cells.

My lab is particularly interested in neurodegeneration and the development of novel therapeutics for neurodegenerative diseases, specifically ALS (Amyotrophic Lateral Sclerosis). At the basic science level, we study the functions of sumoylation in ALS pathogenesis to better understand the basis of neurodegeneration in ALS patients. To this end, we employ multidisciplinary approaches, including biochemistry, biophysics, proteomics, genetics and transgenic animal models.

At the translational science level, our long term goal is to enforce toxic protein clearance from the motor neurons of ALS patients via pharmacological manipulation of sumoylation.