Research Focus

Our major scientific interest lies in 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 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 persisters, 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

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

Julian Eck

cand. med.
WTZ-F room 1.007

Ankit Singh

PhD student
WTZ-F room 1.007

Palaniappan Ramesh

PhD student
WTZ-F room 1.007

Gaurav Borse

PhD student
WTZ-F room 1.011

Siyang Liu

cand. med.
WTZ-F room 1.011

Amal Al Kadi

PhD student
WTZ-F room 1.011

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 immunotherapyJ 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 melanomaGene 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 regressionNature 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