Translational Next Generation Sequencing
1. Drivers of melanoma progression and resistance to therapy (collaboration between Pathology, Dermatology, Bioinformatics Unit CCC, Human Genetics)
Our project aims to identify and characterize genetic and non-genetic alterations of metastatic melanomas with a particular focus on acquired alterations during targeted therapy or immune checkpoint inhibition. As tools, we are using next generation sequencing of commercial and customized melanoma-relevant gene panels, RNA sequencing, immunohistochemistry as well as functional studies. We are currently investigating the effect of genetic alterations on therapy response and tumor immunity.
2. Pathogenesis of cutaneous vascular tumors (Pathology, Dermatology, Bioinformatics Unit CCC)
The human skin can give rise to numerous benign, borderline and malignant tumors. One group investigated by us are neoplasia formed by blood vessels. In particular, we are interested in epithelioid hemangiomas, vascular malformations and angiosarcoma. Our goal is to find genetic aberrations that can be used as therapeutic targets but also to unravel the pathogenesis of these diseases.
Maurus K*, Kosnopfel C*, Kneitz H, Appenzeller S, Schrama D, Glutsch V, Roth S, Gerhard-Hartmann E, Rosenfeldt M, Möhrmann L, Fröhlich M, Hübschmann D, Stenzinger A, Glimm H, Fröhling S, Goebeler M, Rosenwald A, Kutzner H, Schilling B (2021): Cutaneous epithelioid hemangiomas show somatic mutations in the MAPK pathway. Br J Dermatol (epub ahead of print) (2021)
Conway JR, Dietlein F, Taylor-Weiner A, AlDubayan S, Vokes N, Keenan T, Reardon B, Margolis CA, Weirather J, Haq R, Schilling B, Hodi FS, Schadendorf D, Liu D, Van Allen EM (2020): Integrated molecular drivers coordinate biological and clinical states in melanoma. Nat Genet 52:1373-83 (2020)
Jessen C, Kreß JKC, Baluapuri A, Hufnagel A, Schmitz W, Kneitz S, Roth S, Marquardt A, Appenzeller S, Ade CP, Glutsch V, Wobser M, Friedmann-Angeli JP, Mosteo L, Goding CR, Schilling B, Geissinger E, Wolf E, Meierjohann S: The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression. Oncogene 39: 6841-6855 (2020)
Appenzeller S, Gesierich A, Thiem A, Hufnagel A, Jessen C, Kneitz H, Regensburger M, Schmidt C, Zirkenbach V, Bischler T, Schilling B, Siedel C, Goebeler ME, Houben R, Schrama D, Gehrig A, Rost S, Maurus K, Bargou R, Rosenwald A, Schartl M, Goebeler M, Meierjohann S: Identification of patient-specific mutations reveals dual pathway activation in most melanoma patients and activated receptor tyrosine kinases in BRAF/NRAS wildtype melanomas. Cancer 125:586-600 (2019)
Thiem A, Hesbacher S, Kneitz H, di Primio T, Heppt MV; Hermanns HM, Goebeler M, Meierjohann S, Houben R, Schrama: IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression. Journal of Experimental & Clinical Cancer Research 38:397 (2019)