Dr. rer. nat. Renata Varaljai

Research Focus

My research focuses on understanding melanoma evolution, tumor–immune interactions, and treatment-induced adaptation through integrative liquid biopsy and computational approaches. I investigate how dynamic changes in tumor and immune biology can be monitored using circulating biomarkers, including circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), epigenetic biomarkers, and immune-associated soluble factors (e.g., cytokines).

A major focus of my work is the development of multimodal liquid biopsy strategies for longitudinal monitoring of melanoma patients undergoing targeted therapy and immune checkpoint inhibition. By integrating genomic, epigenomic, transcriptomic, inflammatory, and clinical data, I aim to identify biomarkers that predict treatment response, therapy resistance, minimal residual disease, and disease progression.

Within CRC1752 DYNAMO, I investigate how systemic immune dynamics and neutrophil heterogeneity influence response and resistance to immune checkpoint inhibitors in melanoma. My research seeks to identify circulating and tissue-based immune signatures associated with therapeutic outcome and to elucidate how neutrophil-driven remodeling of the tumor microenvironment shapes anti-tumor immunity.

My work combines translational patient cohorts, including clinically annotated longitudinal plasma and tissue cohorts, with statistical and bioinformatic analyses, multi-omic biomarker discovery, and spatial tissue profiling using multiplex immunofluorescence and high-dimensional imaging approaches. Functional validation is performed using in vitro co-culture systems and ex vivo patient- and mouse-derived tumor fragment models (PDTFs and MDTFs), providing complementary platforms to investigate tumor evolution, immune remodeling, and therapeutic response.

By integrating liquid biopsy technologies, computational biology, spatial immunophenotyping, and experimental model systems, my goal is to develop clinically actionable biomarkers and advance precision medicine approaches for melanoma patients.

Current projects:

1. Deciphering neutrophil heterogeneity and its implications for immune checkpoint inhibitor response in melanoma (CRC1752 DYNAMO, Project B06)
2. Leveraging circulating transcriptomic signatures for minimally invasive prediction of disease progression
3. Systemic inflammatory signaling and immune response pathways in melanoma
4. Genetic and epigenetic liquid biopsy approaches for early melanoma detection
5. Multimodal liquid biopsy integration for melanoma monitoring

Key publications:

1. Váraljai R, ZimmerL, Al-Matary Y, Kaptein P, Albrecht LJ, ShannanB, BraseJC, Gusenleitner D, Amaral T, Wyss N, Utikal J, Flatz L, Rambow F, Reinhardt HC, Dick J, Engel DR, Horn S, Ugurel S, Sondermann W, Livingstone E, Sucker A, Paschen A, Zhao F, Placke JM, Klose JM, Fendler WP, Thommen DS, Helfrich I, Schadendorf D, Roesch A.Interleukin-17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma. Nature Cancer 2023 Sept;4(9):1292-1308.doi: 10.1038/s43018-023-00610-2.

2. Albrecht LJ, Höwner A, Griewank K, Lueong SS, Neuhoff N, Horn PA, Sucker A, Paschen A, Livingstone E, Ugurel S, Zimmer L, Horn S, Siveke JT, Schadendorf D, Váraljai R*, Roesch A*. Circulating cell-free messenger RNA enables non-invasive pan-tumor monitoring of melanoma therapy independent of the mutational genotype. Clin Transl Med. 2022 Nov;12(11):e1090. doi: 10.1002/ctm2.1090.
3. Váraljai R*, Horn S, Sucker A, Piercianek D, Schmitt V, Carpinteiro A, Becker KA, Reifenberger J, Roesch A, Felsberg J, Reifenberger G, Sure U, Schadendorf D, Helfrich I. Integrative Genomic Analyses of Patient-Matched Intracranial and Extracranial Metastases Reveal a Novel Brain-Specific Landscape of Genetic Variants in Driver Genes of Malignant Melanoma. Cancers (Basel) 2021 Feb 10; 13(4):731. doi: 10.3390/cancers13040731
4. Váraljai R, Elouali, S, Lueong SS, Wistuba-Hamprecht K, Seremet T, Siveke JT, Becker, JC, Sucker A, Paschen A, Horn PA, Neyns B, Weide B, Schadendorf D, Roesch A. The predictive and prognostic significance of cell-free DNA concentration in melanoma. J Eur Acad Dermatol Venereol. 2021 35: 387-395. doi: 10.1111/jdv.16766
5. Váraljai R, Wistuba-Hamprecht K, Seremet T, Diaz JMS, Nsengimana J, Sucker A, Griewank K, Placke JM, Horn PA, von Neuhoff N, Shannan B, Chauvistré H, Vogel FCE, Horn S, Becker JC, Newton-Bishop J, Stang A, Neyns B, Weide B, Schadendorf D, Roesch A.Application of Circulating Cell-Free Tumor DNA Profiles for Therapeutic Monitoring and Outcome Prediction in Genetically Heterogeneous Metastatic Melanoma. JCO Precis Oncol. 2019 Feb 15;3:PO.18.00229. doi: 10.1200/PO.18.00229
6. Egea-Rodriguez S, Váraljai R, Nordmann TM, Lubis R, Philip M, Rambow F, Roesch A, Flaig M, Horn S, Stoll R, Zhao F, Paschen A, Klebl B, Hickson ID, Schadendorf D, Mann M, Helfrich I. RECQL4 affects MHC class II-mediated signalling and favours an immune-evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melanoma. Clin Transl Med. 2025 Jan;15(1):e70094. doi: 10.1002/ctm2.70094.