G. (Gulce) Sari, PhD

Viruses are responsible for 12-20% of all human cancers and starting from my BSc studies, I have been fascinated by the chess-like battle between the immune system, viruses and tumours. I strongly believe that a better understanding of the molecular events leading to immune escape by viruses and virus-induced cancer is crucial for the development of improved therapeutics.

My education and extensive professional experience have shaped me to become a highly successful immunologist with a special interest in the detailed molecular characterization of immunological processes to study the immune escape mechanisms in chronic hepatitis B virus infections and HBV-related cancer development.

I am currently a postdoctoral researcher in the Immunology of Viral Hepatitis Group at Erasmus Medical Center and I perform thorough molecular and mechanistic characterization of HBV immune evasion to provide the solid basis to increase our overall understanding of virus-host interactions and ultimately yield effective therapeutic intervention strategies.

Viral Immunology, Antigen Presentation, Immunotherapy, Immune Evasion, Cancer

Gulce Sari performed her PhD studies at Erasmus University Medical Center in Rotterdam, The Netherlands between 2017 and 2020.

Projects she was involved in included translational virus-host interaction studies on several mouse models for chronic viral hepatitis, such as chronic HEV infection studies on human liver-chimeric mouse model and the LCMV immunocompetent infection model for the evaluation of novel immunomodulators.

She has performed pre-clinical assessments of the novel immunomodulatory compounds targeting exhausted CD8 T cells in cancer immune evasion or a chronic infectious disease setting. She has also evaluated pegIFNlambda as a new treatment candidate against chronic HEV infections and had a patent now for the treatment chronic HEV infections using pegIFNlambda (Inventor, U.S. Application Nos. 63/119,524 and 63/149,788).

She worked as a postdoctoral researcher at the University of Massachusetts Medical Center, USA between December 2020 and December 2022. Her projects focused on the mechanisms which control the display of foreign antigens to the immune system by MHC class I molecules. Largely independently, she combined CRISPR-Cas9 system with immunological tools and mouse models to address fundamental immunological questions as “What are the (in)direct regulators of MHC I antigen presentation? How do tumours escape the immune detection? Are these mechanisms reversible or a dead-end?”. In the translational part, she identified MHC I related risk factors in immunotherapy resistance of lung cancers and melanomas.

As a senior postdoctoral researcher, in the Viroscience Department at Erasmus MC, she characterized the phenotype, functional characteristics and fine antigen specificity of virus-specific T-cells in HSV-1 infected human corneas and trigeminal ganglia. Using single cell analysis of T-cell receptors and transcriptome in trigeminal ganglia and cornea T cell pools, she determined the fine antigen specificity, function and spatial orientation of dominant CD8 T-cell clones.

She has been working as a postdoctoral researcher in the Gastroenterology and Hepatology Department since August, 2023. Her research here is devoted to understand why immune responses are insufficient to clear hepatitis B virus (HBV) in chronically infected patients, and how anti-viral therapy can revert this. Besides this, she focuses on immune escape mechanisms and how to revert them in the HBV-induced hepatocellular carcinoma.

See also: Orchid.org

1. Sari g and Rock KL. Tumor immune evasion through loss of MHC class-I antigen presentation. Current Opinion in Immunology 83, 102329
2. Sari G*, Zhu J*, Ambardekar C, Yin X, Boonstra A, Feng Z, Vanwolleghem T. The viral open reading frame 3 protein is required for hepatitis E virus fecal shedding and persistent infection in humanized mice. Journal of  Virology 2021; 95:23, e00585-21 (* shared first authorship).
3. Sari G, Mulders CE, Zhu J, van Oord GW, Feng Z, Kreeft-Voermans JJC, Boonstra A, Vanwolleghem T. Treatment induced clearance of HEV by IFN-lambda in liver humanized mice. Liver International 2021; 41(12): 2866–2873.
4. Sari, G., van Oord, G.W., van de Garde, M.D.B., Voermans, J.J.C., Boonstra, A., Vanwolleghem, T., Sexual dimorphism in hepatocyte xenograft models. Cell Transplantation 2021, 30, 09636897211006132.
5. Sari G, Meester EJ, van der Zee LC, Wouters K, van Lennep JR, Peppelenbosch M, Boonstra A, Van der Heiden K, Mulder MMT, Vanwolleghem T. A mouse model of humanized liver shows a human-like lipid profile but does not form atherosclerotic plaque after western type diet. Biochemical and Biophysical Research Communications 2020 pii: S0006-291X(20)30136-4. 
6. Sari G, van de Garde MDB, van Schoonhoven A, Voermans JJC, van der Eijk AA, de Man RA, Boonstra A, Vanwolleghem T, Pas SD. Hepatitis E Virus Shows More Genomic Alterations in Cell Culture than In Vivo. Pathogens 2019 pii: E255. doi:10.3390/pathogens8040255.
7. Januzzi AT, Yilmaz AM, Arslan S, Sari G, Beklen H, Fedorova M, Arga KY, Karademir-Yilmaz B, Alpertunga B. Higher proteotoxic stress rather than mitochondrial damage is involved in higher neurotoxicity of bortezomib compared to carfilzomib. Redox Biology 2020, 101502.
8. Karademir B*, Sari G*, Jannuzzi AT, Musunuri S, Wicher G, Grune T, Mi J, Hacioglu-Bay H, Forsberg-Nilsson K, Bergquist J, Jung T. Proteomic approach for understanding milder neurotoxicity of carfilzomib against Bortezomib. Scientific Reports 2018; 8(1):16318. (* shared first author)
9. Sari G, Okat Z, Sahin A, Karademir B. Proteasome Inhibitors in Cancer Therapy, and their Relation to Redox Regulation. Current Pharmaceutical Design 2018; 24(44):5252-5267.
10. Ozbeyli D, Sari G, Ozkan N, Karademir B, Yüksel M, Sirvanci S, Kasimay O. Effects of different exercise modalities in ovariectomized rats treated with D-galactose. Behavioural Brain Research 2017, doi.org/10.1016/j.bbr.2017.03.044.
11. Sari G, Torcun CC, Grune T, Ozer NK, Karademir B. Proteasome inhibitors in cancer therapy: treatment regiemen and peripheral neuropathy as a side effect. Free Radical Biology & Medicine 2016, 103:1-13.
12. Sari G, Yazar M, Tozkir H, Duymaz J, Gürkan H. Identification of a novel HLA-A*26 allele, HLA-A*26:01:36, in a Turkish family by sequence-based typing. Tissue Antigens 2014, 84(6):580-1. doi: 10.1111/tan.12461.

• 2021 - Nederlandse Vereniging voor Hepatologie (NVH) Thesis Printing Grant
• 2020 - Dutch Society of Immunology (NVVI) Travel Grant
• 2019 - Full Bursary-Young Investigator Award, EASL ILC, Vienna, Austria
• 2016 - Best Oral Presentation, 1st International Cell Death Research Congress, Izmir, Turkey
• 2015 - Young Scientist Award, SFRR-E Meeting, Stuttgart, Germany
• 2015 - Erasmus Staff Training and Mobility Grant
• 2014 - Cooperation in Science and Technology Short Term Scientific Mission Grant