Our laboratory's research is dedicated to investigating intrinsic resistance mechanisms to contemporary (immuno)therapeutic agents, with a particular emphasis on leukemia, though our scope is not limited to this disease alone. We are especially interested in uncovering the (epi)genetic and cellular adaptive responses that are modified during the development of acquired resistance to such treatments. Our goal is to deepen the understanding of how leukemic (and other cancer) cells evade therapeutic interventions, providing insights that could lead to the development of alternative and novel effective treatment strategies.
The foundations of our research group are built on understanding mechanisms by which cancer cells, particularly leukemia cells, develop resistance to current off-the-shelf therapies. We delve into the intricate biology of the cell, drawing on genetics, immunology, and biochemistry to comprehend the complex interplay between them during drug resistance.
Specifically, our current projects investigate the interplay between metabolic regulation and innate nucleic acid receptors in AML during resistance to hypomethylating agents, aiming to identify key pathways and potential therapeutic targets. Additionally, we explore strategies to overcome drug resistance by modulating intrinsic nucleic acid receptor pathways within leukemia cells.
Beyond hematologic malignancies, our research also explores the tumor microenvironment's role in fostering resistance and the ways in which immune modulation can be harnessed to enhance therapeutic efficacy. Through a multidisciplinary approach, we work to collectively advance our understanding of these fundamental processes and hope to contribute to the development of next-generation therapies that can provide more durable and effective responses for patients with relapsed/refractory leukemia as well as other malignancies.
- Czech M*, Schneider S*, Peltokangas N*, El Khawanky N, Ghimire S, Andrieux G, Hülsdünker J, Krausz M, Proietti M, Braun LM, Rückert T, Langenbach M, Schmidt D, Martin I, Wenger V, de Vega E, Haring E, Pourjam M, Pfeifer D, Schmitt-Graeff A, Grimbacher B, Aumann K, Kircher B, Tilg H, Raffatellu M, Thiele Orberg E, Häcker G, Duyster J, Köhler N, Holler E, Nachbaur D, Boerries M, Gerner RR, Grün D, Zeiser R. Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease. Sci Transl Med. 2024 Feb 21;16(735):eadi1501. doi: 10.1126/scitranslmed.adi1501. Epub 2024 Feb 21. PMID: 38381845.
- Vinnakota JM, Biavasco F, Schwabenland M, Chhatbar C, Adams RC, Erny D, Duquesne S, El Khawanky N, Schmidt D, Fetsch V, Zähringer A, Salié H, Athanassopoulos D, Braun LM, Javorniczky NR, Ho JNHG, Kierdorf K, Marks R, Wäsch R, Simonetta F, Andrieux G, Pfeifer D, Monaco G, Capitini C, Fry TJ, Blank T, Blazar BR, Wagner E, Theobald M, Sommer C, Stelljes M, Reicherts C, Jeibmann A, Schittenhelm J, Monoranu CM, Rosenwald A, Kortüm M, Rasche L, Einsele H, Meyer PT, Brumberg J, Völkl S, Mackensen A, Coras R, von Bergwelt-Baildon M, Albert NL, Bartos LM, Brendel M, Holzgreve A, Mack M, Boerries M, Mackall CL, Duyster J, Henneke P, Priller J, Köhler N, Strübing F, Bengsch B, Ruella M, Subklewe M, von Baumgarten L, Gill S, Prinz M, Zeiser R. Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome. Nat Cancer. 2024 May 13. doi: 10.1038/s43018-024-00764-7. PMID: 38741011.
- Maas-Bauer K*, Stell AV*, Yan KL*, de Vega E*, Vinnakota JM*, Unger S, Núñez N, Norona J, Talvard-Balland N, Koßmann S, Schwan C, Miething C, Martens US, Shoumariyeh K, Nestor RP, Duquesne S, Hanke K, Rackiewicz M, Hu Z, El Khawanky N, Taromi S, Andrlova H, Faraidun H, Walter S, Pfeifer D, Follo M, Waldschmidt J, Melchinger W, Rassner M, Wehr C, Schmitt-Graeff A, Halbach S, Liao J, Häcker G, Brummer T, Dengjel J, Andrieux G, Grosse R, Tugues S, Blazar BR, Becher B, Boerries M, Zeiser R. ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease. Nat Commun. 2024 Jan 10;15(1):446. doi: 10.1038/s41467-024-44703-7. PMID: 38199985; PMCID: PMC10781952.
- Marek J, Hanesch L, Krabbe T, El Khawanky N, Heidegger S, Altomonte J. Oncolytic virotherapy with chimeric VSV-NDV synergistically supports RIG-I-dependent checkpoint inhibitor immunotherapy. Mol Ther Oncolytics. 2023 Aug 5;30:117-131. doi: 10.1016/j.omto.2023.08.001. PMID: 37654972; PMCID: PMC10465858.
- El Khawanky N, Hughes A, Yu W, Myburgh R, Matschulla T, Taromi S, Aumann K, Clarson J, Vinnakota JM, Shoumariyeh K, Miething C, Lopez AF, Brown MP, Duyster J, Hein L, Manz MG, Hughes TP, White DL, Yong ASM, Zeiser R. Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia. Nat Commun. 2021 Nov 8;12(1):6436. doi: 10.1038/s41467-021-26683-0. PMID: 34750374; PMCID: PMC8575966.
- Filgueiras IS, Torrentes de Carvalho A, Cunha DP, Mathias da Fonseca DL, El Khawanky N, Freire PP, Cabral-Miranda G, Schimke LF, Camara NOS, Ochs HD, Peron JPS, Cabral-Marques O, de Vasconcelos ZFM. The clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations. PLoS Negl Trop Dis. 2021 Aug 5;15(8):e0009575. doi: 10.1371/journal.pntd.0009575. PMID: 34351896; PMCID: PMC8341629.
- Freire PP, Marques AH, Baiocchi GC, Schimke LF, Fonseca DL, Salgado RC, Filgueiras IS, Napoleao SM, Plaça DR, Akashi KT, Hirata TDC, El Khawanky N, Giil LM, Cabral-Miranda G, Carvalho RF, Ferreira LCS, Condino-Neto A, Nakaya HI, Jurisica I, Ochs HD, Camara NOS, Calich VLG, Cabral-Marques O. The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2-infected patients by sex and age. JCI Insight. 2021 May 24;6(10):e147535. doi: 10.1172/jci.insight.147535. PMID: 34027897; PMCID: PMC8262322.
- Mathew NR, Vinnakota JM, Apostolova P, Erny D, Hamarsheh S, Andrieux G, Kim JS, Hanke K, Goldmann T, Chappell-Maor L, El Khawanky N, Ihorst G, Schmidt D, Duyster J, Finke J, Blank T, Boerries M, Blazar BR, Jung S, Prinz M, Zeiser R. Graft-versus-host disease of the CNS is mediated by TNF upregulation in microglia. J Clin Invest. 2020 Mar 2;130(3):1315-1329. doi: 10.1172/JCI130272. PMID: 31846439; PMCID: PMC7269577.
- Cabral-Marques O, Schimke LF, de Oliveira EB Jr, El Khawanky N, Ramos RN, Al-Ramadi BK, Segundo GRS, Ochs HD, Condino-Neto A. Flow Cytometry Contributions for the Diagnosis and Immunopathological Characterization of Primary Immunodeficiency Diseases With Immune Dysregulation. Front Immunol. 2019 Nov 26;10:2742. doi: 10.3389/fimmu.2019.02742. PMID: 31849949; PMCID: PMC6889851.
- Martin SK, Fitter S*, El Khawanky N*, Grose RH, Walkley CR, Purton LE, Ruegg MA, Hall MN, Gronthos S, Zannettino ACW. mTORC1 plays an important role in osteoblastic regulation of B-lymphopoiesis. Sci Rep. 2018 Sep 28;8(1):14501. doi: 10.1038/s41598-018-32858-5. PMID: 30266921; PMCID: PMC6162303.
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| Name | Position | Phone |
|---|---|---|
| Mikhaleva, Ekaterina | Master Student | +49 89 4140 7932 |
| Shankar, Soundarya | Master Student | +49 89 4140 7932 |
| Wang, Kai | Master Student | +49 89 4140 7932 |
| Zakaria, Zeina | Master Student | +49 89 4140 7932 |
Written applications including CV are welcome and should be forwarded by email to Dr. Nadia El Khawanky.
Dr. El Khawanky supervises Master's Theses every semester. Applications should be forwarded by email to Dr. Nadia El Khawanky.
- European Hematology Association Junior Research Grant
- Wilhelm Sander Stiftung
- TranslaTUM Seed Fund