A5005060569- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Cytokine Signaling Pathways and Interactions
- Genomics and Chromatin Dynamics
- Chronic Lymphocytic Leukemia Research
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Multiple Myeloma Research and Treatments
- Nuclear Structure and Function
- Advanced Breast Cancer Therapies
- Monoclonal and Polyclonal Antibodies Research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- HER2/EGFR in Cancer Research
- Cancer-related Molecular Pathways
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Virus-based gene therapy research
University of Veterinary Medicine Vienna
2015-2024
University of Veterinary Medicine
2020
Ludwig Boltzmann Institute for Cancer Research
2015-2019
Boehringer Ingelheim (Austria)
2017
The transcription factor STAT5 is an essential downstream mediator of many tyrosine kinases (TKs), particularly in hematopoietic cancers. activated by FLT3-ITD, which a constitutively active TK driving the pathogenesis acute myeloid leukemia (AML). Since critical diverse malignant properties AML cells, direct targeting significant clinical value. Here, we describe development and preclinical evaluation novel, potent SH2 domain inhibitor, AC-4-130, can efficiently block pathological levels...
Abstract The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; DM ) in acute leukemia (AML) with a combination of hypermorphic N-terminal mutations ( NT ), promoting expression the leukemia-associated p30 isoform, and amorphic C-terminal mutations. most frequently co-mutated genes AML are GATA2 TET2 , however molecular mechanisms underlying this co-mutational spectrum incomplete. By combining transcriptomic epigenomic analyses - patients models...
Abstract Despite recent approval of targeted drugs for acute myeloid leukemia (AML) therapy, chemotherapy with cytosine arabinoside and anthracyclines remains an important pillar treatment. Both primary secondary resistance are frequent associated poor survival, yet the underlying molecular mechanisms incompletely understood. In previous work, we identified genes deregulated between diagnosis relapse AML, corresponding to therapy naïve resistant states, respectively. Among them was MTSS1 ,...
Abstract The transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis immunity, but their enhanced expression activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, these kinase blockers are not selective against STAT3/5 frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated efficacy of JPX‐0700 JPX‐0750 as dual...
Abstract STAT5 is a member of the signal transducer and activator transcription family proteins widely recognized as an oncogenic master regulator hematological malignancies. To date, therapeutic approaches to attenuate aberrant activity have focused on upstream kinase targets such JAK2, Bcr-Abl, Flt3, Flt3-ITD. there no STAT5-selective inhibitor in clinical development. More recently, PROTAC been deployed successfully against STAT3 isoform demonstrated efficacy safety preclinical models. We...
CRISPR/Cas9 screening has revolutionized functional genomics in biomedical research and is a widely used approach for the identification of genetic dependencies cancer cells. Here, we present an efficient versatile protocol cloning guide RNAs (gRNA) into lentiviral vectors, production supernatants, transduction target cells 96-well format. To assess effect gene knockouts on cellular fitness, describe competition-based cell proliferation assay using flow cytometry, enabling many genes at same...
Abstract The cell dose in umbilical cord blood units is a major determinant for the outcome of hematopoietic transplantation. Prostaglandin analogs and dipeptidylpeptidase-4 (DPP4/CD26)-inhibitors enhance ability stem cells (HSCs) to reconstitute hematopoiesis. Here we explored synergism between treprostinil, stable prostaglandin agonist, DPP4/CD26-inhibitor vildagliptin. combination treprostinil forskolin caused modest but statistically significant increase surface levels DPP4/CD26 on...
ABSTRACT The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; DM ) in acute leukemia (AML) with a combination of hypermorphic N-terminal mutations ( NT ), promoting expression the leukemia-associated p30 isoform, and amorphic C-terminal mutations. most frequently co-mutated genes AML are GATA2 TET2 , however molecular mechanisms underlying this co-mutational spectrum incomplete. By combining transcriptomic epigenomic analyses - patients models...
Abstract Activation of the transcription factor STAT5 is essential for pathogenesis acute myeloid leukemia (AML) containing FLT3 internal tandem duplication (ITD). ITD a constitutively active tyrosine kinase (TK) that drives activation leading to growth and survival AML cells. Although there has been some success in identifying TK inhibitors block function ITD, treatment options are still limited. This mainly due drug resistance development by mutations allow continued STATs. Since...
Background: The transcription factor CCAAT‐enhancer‐binding protein alpha (C/EBPα) is a master regulator of granulopoiesis and regulates the switch between proliferating, uncommitted progenitors cell‐cycle‐arrested, differentiated myeloid cells. Usage two alternative translation initiation sites in CEBPA mRNA results expression full‐length C/EBPα p42 (42 kDa) shorter p30 isoform (30 kDa). mutations are found 9–15% Acute Myeloid Leukemia (AML) patients. N‐terminal frameshift gene lead to...
Abstract NUP98-fusion proteins cause acute myeloid leukemia via unknown molecular mechanisms. All share an intrinsically disordered region (IDR) featuring >35 repeats of Phenylalanine-Glycine (FG) in the NUP98 N-terminus. Conversely, different C-terminal partners are often transcriptional and epigenetic regulators. Given these structural features we hypothesized that mechanisms oncogenic transformation by hard-wired their protein interactomes. Affinity purification coupled to mass...