AG Kalkavan. Lungenkrebs & metastasiertes Uvealmelanom
Cancer Cell Fate Decisions | Immuno-Oncology
Research Focus
Our major scientific interest is dedicated to understanding Cancer Cell Fate Decision Making and how to perturbate such in Cancer Patients. Our key expertise lies within regulated cell death (RCD) and survival pathways as well as tumor immunology. Using lung cancer as a model, we previously identified subpopulations of Drug-Tolerant Persister cancer cells (DTP) that can activate RCD pathways but manage to survive due to the activation of evolutionarily conserved (stress-)responses via cytochrome c. Strikingly, we thereby uncovered a new role for this crucial protein beyond life (electron transport chain) and death (activation of apoptosome), namely survival via direct activation of the Integrated Stress Response. The molecular events, initiated by sublethal cell death engagement and cytochrome c release, govern stress-driven metastatic spread, dormancy, and drug-persistence leading to minimal residual disease.
We further investigate these intrinsic mechanisms of DTPs, as well as the bilateral perturbations between cancer cells and the Tumor (immune) MicroEnvironment (TiME). By studying these diverse processes underlying Cancer Cell Death Resilience, we aim to identify vulnerabilities that we can exploit for Cancer Therapy. In particular, our documented in-depth expertise in these fundamental research areas enables us to address a key question in Immuno-Oncology “what does it take to transform tolerogenic cell death into immunogenic cell death?” a.k.a. “transforming cold tumors into hot ones”.
Group Leader
Dr. med.
Halime Kalkavan
Specialist for internal medicine, hematology and oncology
Lung Cancer & metastatic Uvealmelanoma
CCFD – IO
Dr. med. Halime Kalkavan
University Medicine Essen
Department of Medical Oncology
WTZ-Forschungsgebäude | 1.Etage | Raum 1.044
Hufelandstr. 55
45147 Essen
Tel.: 0201 723 7294
Fax: 0201 723 947 7294
Join our lab
We are actively recruiting talented scientists from all backgrounds and levels of experience. If you are interested in our work, see „Join our lab!“ on how to apply.
Konstanze Schättel
Labmanagement
WTZ-Forschungsgebäude
1.Etage | Raum 1.007
Dr. med.
Maximillian Webendörfer
Amal Al Kadi
PhD student
WTZ-F room 1.011
Gaurav Borse
PhD student
WTZ-F room 1.011
Julian Eck
cand. med.
WTZ-F room 1.007
Jill Kemper
cand. med.
WTZ-F room 1.011
David Kooshani
cand. med.
WTZ-F room 1.007
Siyang Liu
cand. med.
WTZ-F room 1.011
Palaniappan Ramesh
PhD student
WTZ-F room 1.007
Ankit Singh
PhD student
WTZ-F room 1.007
Zaun, G., Liu, S., Webendörfer, M., Wani, A., Rodriguez, D., Green, D.R. & Kalkavan, H.: Protocol for the establishment of murine orthotopic
lung tumors and the assessment of contralateral pulmonal metastasis by flow cytometry. STAR protocols (2025), 6, 103793.
https://www.sciencedirect.com/science/article/pii/S2666166725001996
Ramesh, P., Kadi, A. R. A., Borse, G. M., Webendörfer, M., Zaun, G., Metzenmacher, M., Doerr, F., Bölükbas, S., Hegedüs, B., Lueong, S. S., Magne, J., Liu, B., Nunez, G., Schuler, M., Green, D. R., & Kalkavan, H.: BCL-B Promotes Lung Cancer Invasiveness by Direct Inhibition of BOK. Cells (2025), 14(4), 246. https://doi.org/10.3390/cells14040246
Lever, M., Bogner, S., Giousmas, M., Mairinger, F.D., Baba, H.A., Richly, H., Gromke, T., Schuler, M., Bechrakis, N.E., Kalkavan, H.: Prognostic value of clinical and radiomic parameters in patients with liver metastases from uveal melanoma. Pigment Cell & Melanoma Research (2024). DOI: 10.1111/pcmr.13184
Khan, S. U., Fatima, K., Malik, F.*, Kalkavan, H.* & Wani, A.* Cancer metastasis: Molecular mechanisms and clinical perspectives. Pharmacol. Ther. (2023) doi:10.1016/j.pharmthera.2023.108522
H. Kalkavan, S. Rühl, J.J.P. Shaw & D.R. Green: Non-lethal outcomes of engaging regulated cell death pathways in cancer. Nature Cancer. 1–12 (2023) doi:10.1038/s43018-023-00571-6
H. Kalkavan, M.J. Chen, J.C. Crawford, G. Quarato, P. Fitzgerald, S.W.G. Tait, C.R. Goding, D.R. Green: Sublethal Cytochrome-c release generates drug-tolerant persister cells. Cell. (2022). doi:10.1016/j.cell.2022.07.025
D.A. Rodriguez, G. Quarato, S. Liedmann, B. Tummers, T. Zhang, C. Guy, J. Crawford, G. Palacios, S. Pelletier, H. Kalkavan, P. Fitzgerald, S. Balachandran, D. R. Green: Caspase 8 and FADD repression of cGAS-STING-induced ZBP1 expression controls spontaneous necroptosis. PNAS (2022). doi.org/10.1073/pnas.220724011
L. Such, F. Zhao, D. Liu, B. Thier, V.T.K. Le-Trilling, A. Sucker, C. Coch, N. Pieper, S. Howe, H. Bhat, H. Kalkavan, C. Ritter, R. Brinkhaus, S. Ugurel, J. Köster, U. Seifert, U. Dittmer, M. Schuler, K. S. Lang, T.A. Kufer, G. Hartmann, J.C. Becker, S. Horn, S. Ferrone, D. Liu, E. Van Allen, D. Schadendorf, K. Griewank, M. Trilling, A. Paschen: Targeting RIG-I overcomes melanoma-intrinsic resistance to T cell immunotherapy. J Clin Investigation (2020). doi:10.1172/jci131572
Herbert, K., Binet, R., Lambert, J.-P., Louphrasitthiphol, P., Kalkavan, H., Sesma-Sanz, L., Robles-Espinoza, C. D., Sarkar, S., Suer, E., Andrews, S., Chauhan, J., Roberts, N. D., Middleton, M. R., Gingras, A.-C., Masson, J.-Y., Larue, L., Falletta, P. & Goding, C. R. BRN2 suppresses apoptosis, reprograms DNA damage repair, and is associated with a high somatic mutation burden in melanoma. Gene Dev 33, 310–332 (2019)
Cunha, L. D., Yang, M., Carter, R., Guy, C., Harris, L., Crawford, J. C., Quarato, G., Boada-Romero, E., Kalkavan, H., Johnson, M. D. L., Natarajan, S., Turnis, M. E., Finkelstein, D., Opferman, J. T., Gawad, C. & Green, D. R. LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance. Cell 175, 429-441.e16 (2018)
Kalkavan, H. & Green, D. R. MOMP, cell suicide as a BCL-2 family business. Cell Death and Differentiation 25, 46 (2018). Collection: The Best of Cell Death & Differentiation 2018-2019
Follis, A., Llambi, F., Kalkavan, H., Yao, Y., Phillips, A. H., Park, C.-G., Marassi, F. M., Green, D. R. & Kriwacki, R. W. Regulation of apoptosis by an intrinsically disordered region of Bcl-xL. Nature Chemical Biology 1–8 (2018). doi:10.1038/s41589-018-0011-x
Kalkavan, H., Sharma, P., Kasper, S., Helfrich, I., Pandyra, A. A., Gassa, A., Virchow, I., Flatz, L., Brandenburg, T., Namineni, S., Heikenwalder, M., Höchst, B., Knolle, P. A., Wollmann, G., Laer, D. von, Drexler, I., Rathbun, J., Cannon, P. M., Scheu, S., Bauer, J., Chauhan, J., Häussinger, D., Willimsky, G., Löhning, M., Schadendorf, D., Brandau, S., Schuler, M., Lang, P. A. & Lang, K. S. Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression. Nature Communications 8, ncomms14447 (2017)
Göbel, C., Breitenbuecher, F., Kalkavan, H., Hähnel, P., Kasper, S., Hoffarth, S., Merches, K., Schild, H., Lang, K. & Schuler, M. Functional expression cloning identifies COX-2 as a suppressor of antigen-specific cancer immunity. Cell Death & Disease 5, e1568 (2014)
We are actively recruiting talented scientists from all backgrounds and levels of experience. If you are interested in our work, please contact Dr. Kalkavan.
Students interested in Masterstudent Program or PhD or MD positions as well as Postdocs should include a short cover letter and their CV, any science classes taken, wet lab and/or bioinformatics skills, and references including any previous research mentors.
Please also explain in your email your motivation for joining the lab and career plans.
We thank for funding our research
