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Portrait Charlotte Steenblock

The research group focusses on adult stem cells of the hypothalamus-pituitary-adrenocortical (HPA) axis and their role in restraint and metabolic stress.

Recently, we have identified a novel progenitor population in the adrenal cortex. Under normal homeostasis this Nestin-positive cell population is quiescent but under different forms of stress, we have shown an increase in migration and differentiation into steroid-producing cells.

An imbalance of the stress response has been strongly associated with various health conditions. These include mental disorders such as major depression, anxiety disorders, burnout and somatic manifestations such as dermatitis, and metabolic disorders. Our results indicate that an early sensitization of stem cells of the HPA-axis leading to epigenetic changes might be responsible for this increased risk of developing mental disorders in adulthood. Therefore, we are investigating what happens to stem cells under stress and which signal pathways are involved in the stress response by using animal stress models, RT-qPCR, transcriptomic, proteomic and lipodomic approaches.

In vitro, we are able to isolate these stem cells/ progenitors and differentiate them into steroid-producing cells. The long-term goal is to use such cells for regenerative therapies in order to treat diseases such as adrenal insufficiency.

Last year, we started a second project investigating the impact of metabolic diseases on COVID-19. Metabolic diseases are associated with an increased risk of severe COVID-19 and conversely, new-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients. Analyzing pancreatic autopsy tissue from COVID-19 patients using immunofluorescence, immunohistochemistry, RNA scope and electron microscopy, we detected SARS-CoV-2 viral infiltration of beta-cells in all patients. Using SARS-CoV-2 pseudoviruses, we confirmed that isolated human islet cells are permissive to infection. Even in the absence of manifest new-onset diabetes, necroptotic cell death, immune cell infiltration and SARS-CoV-2 viral infection of pancreatic beta-cells may contribute to varying degrees of metabolic dysregulation in patients with COVID-19.

Charlotte Steenblock Research: Figure
Figure: The stress response is activated by both the hypothalamic-pituitary-adrenocortical axis and the sympatho-adrenomedullary system.

Future Projects and Goals

  • Utilize in vitro differentiated murine embryonic stem cells to restore adrenal insufficiency
  • Evaluate the behavior of progenitors of the hypothalamus-pituitary-adrenal (HPA) axis under perturbations of the HPA axis.
  • Characterization of the molecular dynamics involved in the pathogenesis of stress-associated disorders utilizing omics approaches
  • Characterization of the interplay between metabolic disorders, the neuroendocrine stress axis and COVID-19.

Methodological and Technical Expertise

  • Cell/spheroid cultures of adrenal stem cells
  • Transgenic mice
  • Experimental stress models
  • Fluorescence microscopy
  • RNA and protein biochemistry

Currently Recruiting

Charlotte Steenblock is recruiting in the PhD Fall Selection 2021 (call is closed)

Open Projects
  • Characterization of the interplay between metabolic disorders, the neuroendocrine stress axis and COVID-19.
    Preferred Course of Study/Expertise of Candidate: Cell and Molecular Biology
  • Adrenal stem cells under homeostatic and stress conditions
    Preferred Course of Study/Expertise of Candidate: Cell and Molecular Biology

CV

Charlotte Steenblock née Georgi Jakobsen

Since March 2021
Research group leader at the Dept. of Internal Medicine III, University Clinic Carl Gustav Carus, TU Dresden

2016–2021
Principal investigator at the Dept. of Internal Medicine III, University Clinic Carl Gustav Carus, TU Dresden

2010–2015
Postdoctoral research at Biotec, TU Dresden

2005–2009
Postdoctoral research at Johannes Gutenberg University Clinic, Mainz, Germany

2004–2005
Postdoctoral research at University of Southern Denmark, Denmark

2000–2003
PhD thesis, University of Aarhus/Novozymes A/S, Denmark

1994–2000
Studies of Chemistry and Molecular Biology, University of Aarhus, Denmark (MSc)

More Information

www.uniklinikum-dresden.de

Selected Publications

Steenblock C, Richter S, Berger I, Barovic M, Schmid J, Schubert U, Jarzebska N, von Mässenhausen A, Linkermann A, Schürmann A, Pablik J, Dienemann T, Evert K, Rodionov RN, Semenova NY, Zinserling VA, Gainetdinov RR, Baretton G, Lindemann D, Solimena M, Ludwig B, Bornstein SR
Viral infiltration of pancreatic islets in patients with COVID-19.
Nat Commun. 2021;12(1): 3534

Werdermann M, Berger I, Scriba LD, Santambrogio A, Schlinkert P, Brendel H, Morawietz H, Schedl A, Peitzsch M, King AJF, Andoniadou CL, Bornstein SR, Steenblock C
Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state.
Mol Metab. 2021;43:101112

Steenblock C, Todorov V, Kanczkowski W, Eisenhofer G, Schedl A, Wong ML, Licinio J, Bauer M, Young AH, Gainetdinov RR, Bornstein SR
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Neuroendocrine Stress Axis.
Mol Psychiatry. 2020;25(8):1611–1617

Steenblock C, Rubin de Celis MF, Delgadillo Silva LF, Pawolski V, Brennand A, Werdermann M, Berger I, Santambrogio A, Peitzsch M, Andoniadou CL, Schally AV, Bornstein SR
Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress.
Proc Natl Acad Sci U S A. 2018, 115:12997–13002

Steenblock C, Heckel T, Czupalla C, Espírito Santo AI, Niehage C, Sztacho M, Hoflack B
The Cdc42 guanine nucleotide exchange factor FGD6 coordinates cell polarity and endosomal membrane recycling in osteoclasts.
J Biol Chem. 2014, 289(26):18347–59