Kleiter-lab: Research
Ongoing
Define the role of NR2F6 in ILCs biology during colitis
Research hypothesis
We hypothesize that the nuclear orphan receptor NR2F6 regulates gut ILC development and homeostasis and subsequently influences colitis disease progression in mice and men.
Research design:
The proposed research integrates analysis of ILC cell-intrinsic functions of NR2F6 in development, gut homeostasis, and inflammatory bowel disease (DSS colitis high/low) with a particular focus on NKp46+ILCs. To pinpoint the intrinsic roles of NR2F6 in NKp46+ILCs we will establish a conditional NKp46 (NCR1) cell-specific Nr2f6-deficient mouse line. ILCs will be characterized phenotypically and functionally to reveal underlying mechanisms in vivo and in vitro. As a crucial translational step, we will finally knock out NR2F6 in human HSPCs and explore functional consequences during differentiation under ILC promoting conditions in vitro.
Funded by: ÖGGH Wissenschaftsförderung
(https://www.oeggh.at/preise-foerderungen-stipendien/wissenschaftspreistraeger/)
NR2F6 intrinsic role in anti-tumor NK cell responses
Research question:
How does the nuclear receptor NR2F6 intrinsically govern the development, homeostasis, and function of NKp46+NK and ILC1 cells under steady-state conditions, particularly in the context of cancer disease progression and immune checkpoint blockade (ICB)?
Research design:
This study employs a targeted approach utilizing a conditional NKp46 (NCR1) cell-specific Nr2f6-deficient mouse line. Initially, we aim to assess the impact of NR2F6 deficiency on the development and peripheral homeostasis of NKp46+NK and ILC1 cells as well as their functional capacities. Subsequently, we will explore the anti-tumor activity exhibited by Nr2f6-deficient NKp46+NK and ILC1 cells during cancer progression and metastasis, both in the absence and presence of immune checkpoint inhibition. In a critical translational phase, we will proceed to knockout NR2F6 in primary human NK cells and the human NK-92 cell line, investigating the ensuing functional consequences.
Funded by: Land Tirol & Austrian Science Fund
(https://www.fwf.ac.at/forschungsradar/10.55776/PAT6014624)
(https://www.fwf.ac.at/forschungsradar/10.55776/DOC82)
Publications
https://pubmed.ncbi.nlm.nih.gov/?term=Hermann-Kleiter-N+or+Kleiter-N&sort=pubdate&size=200
Contact
Institute for Cell Genetics
Medical University Innsbruck
Peter-Mayr Str. 1a; A-6020 Innsbruck, Austria/Europe
Tel.: +43(0) 512/9003-70528;
Email: natascha.kleiter@i-med.ac.at
Web: https://www.i-med.ac.at/kleiterLab/
ORCID: https://orcid.org/00000-0003-4389-9813
