Dr. H. Emrah Balcıoğlu

Emrah has worked across multiple disciples at institutions around the world. He earned his double major bachelor’s degree with distinction from departments of Electrical & Electronic Engineering and Physics at Boğaziçi University in Turkey (2008). He then went on to receive his MSc from the Applied Physics and Applied Mathematics Department at Columbia University in the City of New York in the USA (2009). During his MSc studies, he worked under the guidance of Ben O’Shaughnessy, modelling the actin cytoskeleton. For his PhD (2016), he worked under the supervision of Erik Danen in the Department of Toxicology at Leiden University in the Netherlands to invectigate the role of integrin adhesions in cellular mechanotransduction. During his PhD, he also collaborated with Thomas Schmidt’s group, in the Department of Physics of Life Processes to develop imaging and analysis methods. After completing his PhD, he spent two years as a postdoctoral researcher at the Mechanobiology Institute in Singapore under the supervision of Benoit Ladoux to examine the impact of substrate stiffness on collective cell behavior.

Since 2018, Emrah has been based in the Netherlands, using his expertise to understand the interaction between T cells and cancer cells and the tumor microenvironment in solid tumors. T cells are part of the adaptive immune system, identifying and clearing abnormal cells, including virus-infected and tumor cells. Although modifying T cells to recognize tumor cells through chimeric antigen receptors has been effective in treating hematologic cancers, such as diffuse large B cell lymphoma and acute lymphoblastic leukemia, success in solid tumors has been limited. The Laboratory of Tumor Immunology focuses on two main approaches. One is to develop T cell receptor therapies that target germline antigens for solid tumors, with a Phase I MAGE-C2 trial underway for melanoma and head and neck squamous carcinoma and ongoing collaboration with the spin-out company Pan Cancer T to streamline these therapies for various solid tumors. The other approach is to understand the immune mechanisms of response and resistance. These mechanisms are identified through retrospective analysis of archived patient material or through the prospective monitoring of patients receiving (immune) therapies. The TME Facility focuses specifically on extracting spatial information from tissue samples. To develop T cell therapies and better understand identified mechanisms, functional assays are essential. Emrah is working with physicians, biologists, (tumor) immunologists, engineers, and physicists to unravel these mechanisms using two main research lines:

1. Identification of T cell evasion mechanisms in patients
   • Interrogation of immune subsets and mechanisms in multiplex stained and imaged tissues for various tumor types (e.g., TNBC, bladder, oral cavity, multiple myeloma, melanoma)
   • Longitudinal monitoring of T cell subsets in the peripheral blood of oncology patients, such as those treated with monoclonal antibodies (MULTOMAB study)
   • Development of new (machine learning) analysis tools for image and data analysis
2. Development of in vitro assays with functional readouts to identify and target:
   • Shortcomings in T cells in patient solid tumors and their oncogenic drivers
   • Cellular and non-cellular suppressors of T cells in the tumor microenvironment, with a particular focus on the physical properties of the extracellular matrix

References

🠖 2022

• Balcioglu, Hayri E., Rolf Harkes, Erik H. J. Danen, and Thomas Schmidt. 2022. “Substrate Rigidity Modulates Traction Forces and Stoichiometry of Cell–Matrix Adhesions.” The Journal of Chemical Physics 156 (8): 085101. https://doi.org/10.1063/5.0077004.
• Barin, Nastaran, Hayri E. Balcioglu, Iris de Heer, Maurice de Wit, Martine L. M. Lamfers, Martin E. van Royen, Pim J. French, and Angelo Accardo. 2022. “3D‐Engineered Scaffolds to Study Microtubes and Localization of Epidermal Growth Factor Receptor in Patient‐Derived Glioma Cells.” Small 18 (49): 2204485. https://doi.org/10.1002/smll.202204485.
• Phanthunane, Chumut, Rebecca Wijers, Maria De Herdt, Senada Koljenović, Stefan Sleijfer, Robert Baatenburg de Jong, José Hardillo, Reno Debets, and Hayri E. Balcioglu. 2022. “Intratumoral Niches of B Cells and Follicular Helper T Cells, and the Absence of Regulatory T Cells, Associate with Longer Survival in Early-Stage Oral Tongue Cancer Patients.” Cancers 14 (17): 4298. https://doi.org/10.3390/cancers14174298.
• Rijnders, Maud, Hayri E. Balcioglu, Debbie G.J. Robbrecht, Astrid A.M. Oostvogels, Rebecca Wijers, Maureen J.B. Aarts, Paul Hamberg, et al. 2022. “Anti–PD-1 Efficacy in Patients with Metastatic Urothelial Cancer Associates with Intratumoral Juxtaposition of T Helper-Type 1 and CD8+ T Cells.” Clinical Cancer Research 28 (1): 215–26. https://doi.org/10.1158/1078-0432.CCR-20-3319.
• Rijnders, Maud, Debbie G. J. Robbrecht, Astrid A. M. Oostvogels, Mandy van Brakel, Joost L. Boormans, Maureen J. B. Aarts, Hayri E. Balcioglu, et al. 2022. “A Blood-Based Immune Marker for Resistance to Pembrolizumab in Patients with Metastatic Urothelial Cancer.” Cancer Immunology, Immunotherapy, August. https://doi.org/10.1007/s00262-022-03250-0.
• Verploegh, Iris S C, Andrea Conidi, Rutger W W Brouwer, Hayri E. Balcioglu, Panagiotis Karras, Samira Makhzami, Anne Korporaal, et al. 2022. “Comparative Single-Cell RNA-Sequencing Profiling of BMP4-Treated Primary Glioma Cultures Reveals Therapeutic Markers.” Neuro-Oncology 24 (12): 2133–45. https://doi.org/10.1093/neuonc/noac143.

🠖 2021

• Hammerl, Dora, John W.M. M. Martens, Mieke Timmermans, Marcel Smid, Anita M. Trapman-Jansen, Renée Foekens, Olga I. Isaeva, et al. 2021. “Spatial Immunophenotypes Predict Response to Anti-PD1 Treatment and Capture Distinct Paths of T Cell Evasion in Triple Negative Breast Cancer.” Nature Communications 12 (1): 5668. https://doi.org/10.1038/s41467-021-25962-0.
• Mutsaers, Pim, Hayri E. Balcioglu, Rowan Kuiper, Dora Hammerl, Rebecca Wijers, Mark van Duin, Bronno van der Holt, et al. 2021. “V-Domain Ig Suppressor of T Cell Activation (VISTA) Expression Is an Independent Prognostic Factor in Multiple Myeloma.” Cancers 13 (9): 2219. https://doi.org/10.3390/cancers13092219.
• Phanthunane, C., R. Wijers, M. de Herdt, T.P.M. Langeveld, S. Koljenovic, S. Dasgupta, S. Sleijfer, et al. 2021. “B-Cell Clusters at the Invasive Margin Associate with Longer Survival in Early-Stage Oral-Tongue Cancer Patients.” OncoImmunology 10 (1): 1882743. https://doi.org/10.1080/2162402X.2021.1882743.

🠖 2020

• Balcioglu, Hayri E., Lakshmi Balasubramaniam, Tomita Vasilica Stirbat, Bryant L. Doss, Marc-Antoine Fardin, René-Marc Mège, and Benoit Ladoux. 2020. “A Subtle Relationship between Substrate Stiffness and Collective Migration of Cell Clusters.” Soft Matter 16 (7): 1825–39. https://doi.org/10.1039/C9SM01893J.

🠖 2019

• Kunert, Andre, Edwin A. Basak, Daan P. Hurkmans, Hayri E. Balcioglu, Yarne Klaver, Mandy van Brakel, Astrid A. M. Oostvogels, et al. 2019. “CD45RA+CCR7− CD8 T Cells Lacking Co-Stimulatory Receptors Demonstrate Enhanced Frequency in Peripheral Blood of NSCLC Patients Responding to Nivolumab.” Journal for ImmunoTherapy of Cancer 7 (1): 149. https://doi.org/10.1186/s40425-019-0608-y.
• Yeo, Subhash, Suda, Balcıoğlu, Zhou, Thuya, Loh, et al. 2019. “FBXW5 Promotes Tumorigenesis and Metastasis in Gastric Cancer via Activation of the FAK-Src Signaling Pathway.” Cancers 11 (6): 836. https://doi.org/10.3390/cancers11060836.

🠖 2018

• Pomp, Wim, Koen Schakenraad, Hayri E. Balcıoğlu, Hedde van Hoorn, Erik H. J. Danen, Roeland M.H. Merks, Thomas Schmidt, and Luca Giomi. 2018. “Cytoskeletal Anisotropy Controls Geometry and Forces of Adherent Cells.” Physical Review Letters 121 (17): 178101. https://doi.org/10.1103/PhysRevLett.121.178101.
• Seddiki, Rima, Gautham Hari Narayana Sankara Narayana, Pierre-Olivier Strale, Hayri Emrah Balcioglu, Grégoire Peyret, Mingxi Yao, Anh Phuong Le, et al. 2018. “Force-Dependent Binding of Vinculin to α-Catenin Regulates Cell–Cell Contact Stability and Collective Cell Behavior.” Edited by Manuel Théry. Molecular Biology of the Cell 29 (4): 380–88. https://doi.org/10.1091/mbc.E17-04-0231.

🠖 prior to 2018

• Balcioglu, Hayri E., Hedde van Hoorn, Dominique M. Donato, Thomas Schmidt, and Erik H. J. Danen. 2015. “The Integrin Expression Profile Modulates Orientation and Dynamics of Force Transmission at Cell–Matrix Adhesions.” Journal of Cell Science 128 (7): 1316–26. https://doi.org/10.1242/jcs.156950.
• Balcioglu, Hayri E., Bob van de Water, and Erik H.J. J. Danen. 2016. “Tumor-Induced Remote ECM Network Orientation Steers Angiogenesis.” Scientific Reports 6 (1): 22580. https://doi.org/10.1038/srep22580.
• Fokkelman, Michiel, Hayri E. Balcıoğlu, Janna E. Klip, Kuan Yan, Fons J. Verbeek, Erik H. J. Danen, and Bob van de Water. 2016. “Cellular Adhesome Screen Identifies Critical Modulators of Focal Adhesion Dynamics, Cellular Traction Forces and Cell Migration Behaviour.” Scientific Reports 6 (1): 31707. https://doi.org/10.1038/srep31707.
• Jansen, Karin A., Dominique M. Donato, Hayri E. Balcioglu, Thomas Schmidt, Erik H.J. Danen, and Gijsje H. Koenderink. 2015. “A Guide to Mechanobiology: Where Biology and Physics Meet.” Biochimica et Biophysica Acta (BBA) – Molecular Cell Research 1853 (11): 3043–52. https://doi.org/10.1016/j.bbamcr.2015.05.007.
• Stachowiak, Matthew R., Patrick M. McCall, Todd Thoresen, Hayri E. Balcioglu, Lisa Kasiewicz, Margaret L. Gardel, and Ben O’Shaughnessy. 2012. “Self-Organization of Myosin II in Reconstituted Actomyosin Bundles.” Biophysical Journal 103 (6): 1265–74. https://doi.org/10.1016/j.bpj.2012.08.028.
• Stachowiak, Matthew R., Mark A. Smith, Elizabeth Blankman, Laura M. Chapin, Hayri E. Balcioglu, Shuyuan Wang, Mary C. Beckerle, and Ben O’Shaughnessy. 2014. “A Mechanical-Biochemical Feedback Loop Regulates Remodeling in the Actin Cytoskeleton.” Proceedings of the National Academy of Sciences 111 (49): 17528–33. https://doi.org/10.1073/pnas.1417686111.
• Truong, Hoa H., Jiangling Xiong, Veerander P. S. Ghotra, Ella Nirmala, Lizette Haazen, Sylvia E. Le Dévédec, Hayri E. Balcioğlu, et al. 2014. “β 1 Integrin Inhibition Elicits a Prometastatic Switch Through the TGFβ–MiR-200–ZEB Network in E-Cadherin–Positive Triple-Negative Breast Cancer.” Science Signaling 7 (312). https://doi.org/10.1126/scisignal.2004751.
• Xiong, Jiangling, Hayri E. Balcioglu, and Erik H.J. Danen. 2013. “Integrin Signaling in Control of Tumor Growth and Progression.” The International Journal of Biochemistry & Cell Biology 45 (5): 1012–15. https://doi.org/10.1016/j.biocel.2013.02.005.