Systems Immunology: Dynamics across Cellular Scales beyond Tissue Boundaries

Research Group Leader:

Lorenz Adlung, Ph.D.
I. Medizinische Klinik und Poliklinik
Universitätsklinikum Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Tel.: +49-40-7410-xxxxx
E-Mail: lorenz.adlung@uke.de

Scheme_Adlung_Lab

Project description

Inflammation and tissue repair are tightly intertwined processes with a complex regulatory network of underlying cellular and molecular signatures. The gradual transition between these states relies on a dynamic change of cellular functions and interactions in space and time. Studying these transitions may unravel mechanistic links between physiological tissue maintenance and protection from pathological deteriorations. Rational interventions into these processes will likely aid the personalized prevention and treatment of an array of diseases ranging from autoimmune disorders to carcinogenic malignancies.

A current challenge in clinical practice is the limited availability of human biopsies from the tissue of interest in a time-resolved manner, e.g. before and during treatment. Lack of such data hampers our understanding of sustained organ health or disease onset and progression, respectively. We aim to overcome these limitations by a systems biology approach combining cutting-edge experimental technologies with computational modelling. Global high-throughput screenings on the molecular and cellular level are complemented by targeted measurements to derive predictions and perform validation experiments. The ultimate goal of this approach is to inform treatment and guide clinical decision-making.

We aim to utilize the liver as paradigm to study the balance between inflammatory responses and tissue regeneration. For instance, in the context of autoimmune hepatitis, we are exploring to which extent immune cells in the peripheral blood stream are indicative of the liver tissue environment and if these cells, which are easily accessible along treatment course, are indicative of disease progression. Since inflammation and tissue repair rely on a conserved functional program, we are also investigating these processes in other organ systems to learn more about regulatory principles. Recently, we discovered Lipid-Associated Macrophage (LAM) Cells in the epididymal adipose tissue and found them to be present in liver steatosis, too (Jaitin*, Adlung* et al., Cell 2019). Our hypothesis is that LAM Cells harbor the potential for tissue protection and repair, thereby opposing inflammatory damage in the liver.

General questions of interest:

• How does cellular signal transduction determine cell fate?
• What are causes and consequences of immune cells’ phenotypic plasticity?
• How to link clinical metadata and host cellular and microbial dynamics to infer physiological and pathological properties?

Key methods:

• single-cell and bulk RNA-sequencing of murine and human material for discovery
• ex-vivo cultivation experiments and biochemistry assays for validation
• deterministic and statistical computational modelling for predictions

News:

The Adlung Lab will officially launch on 01.07.2021.

On our interdisciplinary quest, we are always looking for highly motivated individuals to join us.
Please see Open Positions. We encourage particularly people from diverse backgrounds to apply.

Tuganbaev T, Mor U, Bashiardes S, Liwinski T, Nobs SP, Leshem A, Dori-Bachash M, Thaiss CA, Pinker EY, Ratiner K, Adlung L, Federici S, Kleimeyer C, Moresi C, Yamada T, Cohen Y, Zhang X, Massalha H, Massasa E, Kuperman Y, Koni PA, Harmelin A, Gao N, Itzkovitz S, Honda K, Shapiro H, Elinav E.

Diet Diurnally Regulates Small Intestinal Microbiome-Epithelial-Immune Homeostasis and Enteritis
Cell. 2020 Sep 17;182(6):1441-1459.e21. doi: 10.1016/j.cell.2020.08.027.

Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B, Descamps H, Lundgren P, Bleriot C, Liu Z, Deczkowska A, Keren-Shaul H, David E, Zmora N, Eldar SM, Lubezky N, Shibolet O, Hill DA, Lazar MA, Colonna M, Ginhoux F, Shapiro H, Elinav E, Amit I.

Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner.
Cell. 2019 Jul 25;178(3):686-698.e14. doi: 10.1016/j.cell.2019.05.054.

Adlung L, Kar S, Wagner MC, She B, Chakraborty S, Bao J, Lattermann S, Boerries M, Busch H, Wuchter P, Ho AD, Timmer J, Schilling M, Höfer T, Klingmüller U.

Protein abundance of AKT and ERK pathway components governs cell type-specific regulation of proliferation.
Mol Syst Biol. 2017 Jan 24;13(1):904. doi: 10.15252/msb.20167258.

Wolf D, Rippa V, Mobarec JC, Sauer P, Adlung L, Kolb P, Bischofs IB.

The quorum-sensing regulator ComA from Bacillus subtilis activates transcription using topologically distinct DNA motifs.
Nucleic Acids Res. 2016 Mar 18;44(5):2160-72. doi: 10.1093/nar/gkv1242.

Raue A, Steiert B, Schelker M, Kreutz C, Maiwald T, Hass H, Vanlier J, Tönsing C, Adlung L, Engesser R, Mader W, Heinemann T, Hasenauer J, Schilling M, Höfer T, Klipp E, Theis F, Klingmüller U, Schöberl B, Timmer J.

Data2Dynamics: a modeling environment tailored to parameter estimation in dynamical systems.
Bioinformatics. 2015 Nov 1;31(21):3558-60. doi: 10.1093/bioinformatics/btv405.

Boehm ME, Adlung L, Schilling M, Roth S, Klingmüller U, Lehmann WD.

Identification of isoform-specific dynamics in phosphorylation-dependent STAT5 dimerization by quantitative mass spectrometry and mathematical modeling.
J Proteome Res. 2014 Dec 5;13(12):5685-94. doi: 10.1021/pr5006923.


Beer R, Herbst K, Ignatiadis N, Kats I, Adlung L, Meyer H, Niopek D, Christiansen T, Georgi F, Kurzawa N, Meichsner J, Rabe S, Riedel A, Sachs J, Schessner J, Schmidt F, Walch P, Niopek K, Heinemann T, Eils R, Di Ventura B.

Creating functional engineered variants of the single-module non-ribosomal peptide synthetase IndC by T domain Exchange.
Mol Biosyst. 2014 Jul;10(7):1709-18. doi: 10.1039/c3mb70594c.