Caroline Hutter Group
LCH - the disease
LCH is a rare histiocytic disorder that may affect any age group, but its most severe clinical course predominantly affects young children. LCH has a wide spectrum of clinical manifestations ranging from single bone lesions, which often regress spontaneously, to severe, sometimes life-threatening multi-system disease, which requires intensive therapy. The etiology of LCH is not known, although it is currently regarded as MAPK-pathway-driven myeloid neoplasm by many.
We are particularly interested in the way LCH lesions are composed since we have evidence for considerable cellular heterogeneity within LCH lesions, pointing towards a developmental hierarchy. We are dissecting the composition of LCH samples by applying next-generation sequencing techniques and flow analysis. In addition, we are analyzing peripheral blood of patients diagnosed with LCH to characterize circulating cells associated with this disease. We have also established an in vitro model system for LCH using peripheral blood monocytes which can be differentiated in the presence of Notch ligands in LCH-like cells. This system can be used to analyze signaling pathways involved in the disease. We are currently focusing on the role of the Notch signaling pathway and its potential impact on LCH development, because our previous work suggests that this pathway might be important in LCH pathogenesis. In an important translational project we aim to develop biomarkers that can be used to determine high-risk disease at time of diagnosis and to evaluate treatment response. To do this, we are tracking the level of LCH-associated mutations in the peripheral blood of patients with LCH at time of diagnosis and during treatment. If successful, these biomarkers would fundamentally change diagnosis and enable targeted treatment of children with LCH. To this end, we are collaborating closely with investigators and clinicians worldwide.
- Halbritter F, Farlik M, Schwentner R, Jug G, Fortelny N, Schnoller T, Pisa H, Schuster LC, Reinprecht A, Czech T, Gojo J, Holter W, Minkov M, Bauer WM, Simonitsch-Klupp I, Bock C, Hutter C. Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis. Cancer Discov. 2019 Jul 25. pii: CD-19-0138.
- Schwentner R, Jug G, Kauer MO, Schnöller T, Waidhofer-Söllner P, Holter W, Hutter C. JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans cell histiocytosis-like cells. J Leukoc Biol. 2019 Jan;105(1):101-111.
- Schwentner R, Kolenová A, Jug G, Schnöller T, Ahlmann M, Meister B, Lehrnbecher T, Minkov M, Hutter C. Longitudinal assessment of peripheral blood BRAFV600E levels in patients with Langerhans cell histiocytosis. Pediatr Res. 2018 Nov 24.
- Kolenová A, Schwentner R, Jug G, Simonitsch-Klupp I, Kornauth C, Plank L, Horáková J, Bodová I, Sýkora T, Geczová L, Holter W, Minkov M, Hutter C. Targeted inhibition of the MAPK pathway: emerging salvage option for progressive life-threatening multisystem LCH. Blood Advances. 2017; 1, 352-356.
- Hutter C, Minkov M. Insights into the pathogenesis of Langerhans cell histiocytosis: the development of targeted therapies. Immunotargets Ther. 2016 Oct 12;5:81-91.
- Hutter C, Kauer M, Simonitsch-Klupp I, Jug G, Schwentner R, Leitner J, Bock P, Steinberger P, Bauer W, Carlesso N, Minkov M, Gadner H, Stingl G, Kovar H, Kriehuber E. Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells. Blood. 2012;120(26):5199-208
Team Pathobiology of LCH
DDr. Caroline Hutter (MD PhD)
Group Leadercaroline.hutter(at)stanna.at +43 1 40470 4043
Sebastian Eder, MD, BSc
Bioinformatics, clinical researchsebastian.eder(at)stanna.at +43 1 40170 9169
Raphaela Schwentner, PhD
Postdoctoral Fellowraphaela.schwentner(at)ccri.at +43 1 40470 4042
Eva Krivec, MSc
eva.krivec(at)ccri.at +43 1 40470 4043
Giulio Abgnale, PhD
+43 1 40470 4042
Wouter Van Midden, MSc
wouter.van-midden(at)ccri.at +43 1 40470 4043