Lung Cancer & metastatic Uvealmelanoma

Dr. Kalkavan is an Advanced Physician Scientist with an exceptional dedication to biomedical research. She is a consulting physician in haemato-oncology and internal medicine, experienced in clinical trials from phase I to III. Her major scientific discoveries and advancements are in the fields of molecular cancer cell biology and tumor-immunology. Her seminal work on anti-tumoral immunity elicited by non-cytopathic viruses provided the basis for an academic spin-off, with the aim to bring this novel treatment approach to cancer patients. In Professor Dr. Douglas Green’s Lab in the Department of Immunology at St. Jude Children’s Research Hospital (Memphis, TN) she explored the phenomenon of drug-tolerant persister cells in cancer. She discovered that the engagement of the core apoptotic machinery drives the properties of such persisters by the activation of the Integrated Stress Response (ISR) and thereby increases cancer aggressiveness.

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 engagement of evolutionarily conserved (stress-)responses. These molecular events 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”.

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.