JakStat Monarchies

Jak-Stat

One of the world's leading research groups, studying signal transmission by JAKs and STATs.

For over a decade, the Consortium has been funded as a Special Research Program (SFB) by the Austrian Science Fund (FWF). It has made substantial contributions to the current understanding of the functions of Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) in homeostasis and disease. This progress has been fuelled largely by the generation and analysis of advanced transgenic mouse models for a number of human disorders, such as haematopoietic malignancies as well as infectious, inflammatory, and metabolic diseases.

Today, the JAK-STAT pathway is recognised as one of the twelve core pathways in the initiation and progression of cancer and a central communication node for the immune system.

Our Mission

Seven internationally competitive research teams in Vienna join forces to deploy next-generation sequencing and proteome technologies based on strong bioinformatics competence. We share the vision of advancing the knowledge of chromatin architectures that govern (patho)-physiological processes. JAK-STAT serves as a paradigm to identify hierarchies, key players ('monarchs'), and co-factors shaping the chromatin landscapes of hematopoietic immune cells and structural non-immune cells under healthy and diseased conditions. The chromatin architecture of these cells defines their transcriptional profiles that are either a prerequisite for or a consequence of, disease.

Our Research Areas

Infection, Immunity & Inflammation

The research area focuses on JAK-STAT function in haematopoietic and structural cells after immune-, inflammation- or stress-related stimuli. We investigate STATs 1 (incl. isoforms), 2, 3, 5 shaping the chromatin activities of bone marrow derived and tissue resident macrophages under homeostatic and differentiation conditions as well as upon infection with microbes. The impact of the JAK family member Tyrosine Kinase 2 (TYK2) on the gene control layers of naïve immune cells and the crosstalk between immune cells is the other focal point.

Hematopoietic Malignancies

Constitutive JAK and/or STAT activation is found in most myeloproliferative neoplasms and in many other hematopoietic malignancies. It is frequently a biomarker of poor prognosis. The underlying molecular aberrations include activating mutations in or overexpression of signaling components (cytokine receptor, JAK, STAT), or rare JAK fusion proteins.

Homeostatic Cell Type – Specific Regulation

Cellular and tissue homeostasis is the result of variables being regulated on chromatin level such that the internal environment remains stable and fairly constant even though the external environment varies. Cell type-specific homeostatic chromatin landscapes are maintained by tonic (constitutive) signals
provided by auto- and paracrine acting cytokines and growth factors as well as by cell-cell contacts. All SFB members contribute to the generation of a map of the JAK-STAT-shaped chromatin landscape of various hematopoietic and structural cell types under homeostatic in comparison to stressed or diseased conditions.