Solute Carriers in cancer
Arbeitsgruppe Dr. Ruth Eichner
Research Interests
Solute Carrier proteins (SLCs) are the largest family of membrane transporters in the human genome. They orchestrate the import and export of nutrients and metabolites and therefore play a key role in cellular metabolism and growth. In cancer, SLCs are frequently overexpressed to meet the increased metabolic needs of malignant cells. Next to their potential as therapeutic targets, they also play important roles as drug transporters and as mediators of established anti-cancer agents.
Our lab focuses primarily on cell surface SLCs in hematological malignancies such as leukemia, lymphoma or myeloma. We are interested in elucidating the (aberrant) proteostatic and metabolic regulation driving their expression in cancer as well as their impact on cellular differentiation, cancer initiation and progression. Based on these mechanistic insights, we aim to establish respectivce SLCs as biomarkers and therapeutic targets alone or as part of combinatorial approaches to improve and broaden the diagnostic and therapeutic possibilities in hematological cancer. To achieve this, we combine various approaches from genetic screens via proteomics and metabolics analyses to imaging studies, advanced protein biochemistry and cell biological methods. Analyses of patient-derived primary material and preclinical mouse models complement the experimental spectrum and strengthen the translational impact.
Heider M, Eichner R, Stroh J, Morath V, Kuisl A, Zecha J, Lawatscheck J, Baek K, Garz AK, Rudelius M, Deuschle FC, Keller U, Lemeer S, Verbeek M, Götze KS, Skerra A, Weber WA, Buchner J, Schulman BA, Kuster B, Fernándes-Sáiz V, Bassermann F. The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma. Mol Cell. 2021 Feb 3:S1097-2765(20)30988-6. doi:10.1016/j.molcel.2020.12.046. Online ahead of print.
Eichner R, Fernández-Sáiz V, Targosz BS, Bassermann F. Cross Talk Networks of Mammalian Target of Rapamycin Signaling With the Ubiquitin Proteasome System and Their Clinical Implications in Multiple Myeloma. Int Rev Cell Mol Biol. 2019;343:219-297. Review.
Sedlyarov V*, Eichner R*, Girardi E, Essletzbichler P, Goldmann U, Nunes-Hasler P, Srndic I, Moskovskich A, Heinz LX, Kartnig F, Bigenzahn JW, Rebsamen M, Kovarik P, Demaurex N, Superti-Furga G. The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. Cell Host Microbe. 2018 Jun 13;23(6):766-774. *equal contribution
Hashimoto M, Girardi E, Eichner R, Superti-Furga G. Detection of Chemical Engagement of Solute Carrier Proteins by a Cellular Thermal Shift Assay. ACS Chem Biol. 2018 Jun 15;13(6):1480-1486.
Eichner R, Heider M, Fernández-Sáiz V, van Bebber F, Garz AK, Leemer S, Rudelius M, Targosz BS, Jacobs L, Knorn AM, Slawska J, Platzbecker U, Germing U, Langer C, Knop S, Einsele H, Peschel C, Haass C, Keller U, Schmid B, Götze KS, Kuster B, Bassermann F. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to extert antitumor activity and teratogenicity. Nat Med. 2016 Jul;22(7):735-43.
Bassermann F, Eichner R, Pagano M. The ubiquitin proteasome system - implications for call cycle control and the targeted treatment of cancer. Biochim Biophys Acta. 2014 Jan;1843(1):150-62. Review.
Fernández-Sáiz V, Targosz BS, Lemeer S, Eichner R, Langer C, Bullinger L, Reiter C, Slotta-Huspenina J, Schroeder S, Knorn AM, Kurutz J, Peschel C, Pagano M, Kuster B, Bassermann F. SCFFbxo9 and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma. Nat Call Biol. 2013 Jan;15(1):72-81.
Puissegur MP*, Eichner R*, Quelen C, Coyaud E, Mari B, Lebrigand K, Broccardo C, Nguyen-Khc F, Bousquet M, Brousset P. B-cell regulator of immunoglobulin heavy-chain-transcription (Bright)/ARID3a is a direct target of the oncomir microRNA-125b in progenitor B-cells. Leukemia. 2012 Oct;26(10):2224-32. * equal contribution
Stroh, J., Seckinger, A., Heider, M., Rudelius, M., Eichner, R., Schick, M., Slawska, J., Emde, M., Salwender, H., Bertsch, U., et al. (2022). MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma. Blood Adv. 6(2):515-520. doi:10.1182/bloodadvances.2021005532.
Kornauth, C., Pemovska, T.,Vladimer, G.I., Bayer, G., Bergmann, M., Eder, S., Eichner, R., Erl, M., Esterbauer, H., Exner, R., et al. (2022). Functional precision medicine provides clinical benefit in advanced aggressive hematological cancers and identifies exceptional responders. Cancer Discov. 12(2):372-387. doi: 10.1158/2159-8290.CD-21-0538.
Promotionsprogramm "Translationale Medizin", TU München
Deutsche Jose Carreras Leukämiestiftung
Deutsche Krebshilfe
DFG (FOR 5560)
TranslaTUM Seedfund
Principal Investigator
Dr. med. Ruth Eichner, Ph.D. M.Sc.
E-Mail(link sends e-mail)
Laboratory:
Center for Translational Cancer Research (TranslaTUM)
Lab Members (alphabetical)
Carla Bühring-Uhle, M.D. student
Dr. med. sci. Michael Dietachmayr, Resident & Postdoc
Mohamed Elbahloul, M.Sc., PhD-Student
Eva Henkel, B.Sc. Technician
Dr. med. sci. Manuel Knauer, Resident & Postdoc
Cosima Nather, M.D. student
Paul Smit, M.D. student
Application
With regard to scientific positions or internships, written applications including CV are welcome and should be forwarded by e-mail to Dr. Ruth Eichner.