Translational Myeloma Research Group

The Translational Myeloma Research Group of the Heidelberg Myeloma Center focuses on molecular and pathophysiologic aspects of multiple myeloma, with special interest in mechanisms of drug resistance, spatial heterogeneity of clonal evolution, and novel therapeutic targets.

Current treatment strategies against multiple myeloma are based on a combination of proteasome inhibitors, immune modulatory drugs, and monoclonal antibodies, as well as chemotherapy with autologous stem cell transplantation. Despite improved survival rates, long term remission or even cure is still rarely achieved. Personalizing tumor specific therapy is currently explored to improve the outcome of specific patient groups by correlating genomic, proteomic and clinical data of refractory myeloma patients.

In order to understand mechanisms underlying drug resistance in multiple myeloma, we compare the evolution of the clonal structure of tumor cells along treatment in clinical trials and routine care with the aim to discover novel therapeutic targets in refractory disease. By combining NGS-based readouts (WGS, RNAseq, scRNAseq, scATACseq, CiteSeq) with proteome-based technologies we comprehensively map cellular signaling profiles in order to identify biomarkers as well as novel therapeutic targets. We further focus on tumor heterogeneity within individual multiple myeloma patients to understand the full spectrum of disease biology and specifically the role of residual tumor cells in clinical remission.

Overall, our goal is to understand the complex processes underlying the heterogeneity of this disease. We aim to discover molecular mechanisms that lead to drug resistance, impairment of the immune microenvironment, and result in novel therapeutic targets. Due to our strong clinical affiliation with the University Hospital, we successfully translate our discoveries in clinical application.

The Translational Myeloma Research Group

Our Team

7 Employees

Prof. Dr. Marc-Steffen Raab

Group Leader - Translational Myeloma Research Group

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Anja Baumann

Technician

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Carolin Kolb

Technician

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Jennifer Rohleder

Technician

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Alexandra Poos

Postdoc

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Nina Prokoph

Postdoc

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Julia Lorenz

MD student

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Publications (selected)

2024 - Journal of Clinical Oncology. (Online ahead of print)

Genomic Classification and Individualized Prognosis in Multiple Myeloma.

Maura F, Rajanna AR, Ziccheddu B, Poos AM, Derkach A, Maclachlan K, Durante M, Diamond B, Papadimitriou M, Davies F, Boyle EM, Walker B, Hultcrantz M, Silva A, Hampton O, Teer JK, Siegel EM, Bolli N, Jackson GH, Kaiser M, Pawlyn C, Cook G, Kazandjian D, Stein C, Chesi M, Bergsagel L, Mai EK, Goldschmidt H, Weisel KC, Fenk R, Raab MS, Van Rhee F, Usmani S, Shain KH, Weinhold N, Morgan G, Landgren O

2023 - Nature Communications 14(1): 5011.

Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level.

John L, Poos AM, Brobeil A, Schinke C, Huhn S, Prokoph N, Lutz R, Wagner B, Zangari M, Tirier SM, Mallm JP, Schumacher S, Vonficht D, Solé-Boldo L, Quick S, Steiger S, Przybilla MJ, Bauer K, Baumann A, Hemmer S, Rehnitz C, Lückerath C, Sachpekidis C, Mechtersheimer G, Haberkorn U, Dimitrakopoulou-Strauss A, Reichert P, Barlogie B, Müller-Tidow C, Goldschmidt H, Hillengass J, Rasche L, Haas SF, van Rhee F, Rippe K, Raab MS, Sauer S, Weinhold N

2023 - Blood. (Epub ahead of print).

Resolving therapy resistance mechanisms in multiple myeloma by multi-omics subclone analysis.

Poos AM, Prokoph N, Przybilla MJ, Mallm JP, Steiger S, Seufert I, John L, Tirier SM, Bauer K, Baumann A, Rohleder J, Munawar U, Rasche L, Kortüm KM, Giesen N, Reichert P, Huhn S, Müller-Tidow C, Goldschmidt H, Stegle O, Raab MS, Rippe K, Weinhold N

2023 - Leukemia 37(6):1349-1360.

Preclinical discovery and initial clinical data of WVT078, a BCMA × CD3 bispecific antibody.

Raab MS, Cohen YC, Schjesvold F, Aardalen K, Oka A, Spencer A, Wermke M, Souza AD, Kaufman JL, et al.

2023 - Cancer Cell 41(4):711-725.

The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients.

Friedrich MJ, Neri P, Kehl N, Michel J, Steiger S, Kilian M, Leblay N, Maity R, Sankowski R, Lee H, Barakat E, Ahn S, Weinhold N, Rippe K, Bunse L, Platten M, Goldschmidt H, Müller-Tidow C, Raab MS, Bahlis NJ

2023 - Blood 141(14):1685-1690.

A phase II clinical trial of combined BRAF/MEK inhibition for BRAFV600E-mutated multiple myeloma.

Giesen N, Chatterjee M, Scheid C, Poos AM, Besemer B, Miah K, Benner A, Becker N, et al.

2021 - Nature Communications 12(1):6960.

Subclone-specific microenvironmental impact and drug response in refractory multiple myeloma revealed by single-cell transcriptomics.

Tirier SM, Mallm JP, Steiger S, Poos AM, Awwad MHS, Giesen N, Casiraghi N, Susak H, et al.

2018 - The New England Journal of Medicine 379(19):1811-1822.

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma.

Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, Leleu X, LeBlanc R, Suzuki K, Raab MS, et al.