News

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June 2021

Study published: Transglutaminase 2 promotes colon cancer cell survival - congrats to Patrizia and Ilaria

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June 2021

Esther defended her thesis - Well done Dr. med.!

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May 2021

Michael published Editorial on CHIP

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March 2021

New study published on clonal hematopoiesis - big congrats to Katharina

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Jan 2021

Lena successfully defended her thesis - congrats Dr. Dorsheimer

Nov 2020

Alec Gessner joint the team as PhD student - welcome Alec!

July 2020

New positions available in the lab!

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June 2020

Fighting COVID19 - support by Goethe Corona Fonds

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April 2020

Joining the BD MultiOmics Alliance

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March 2020

New PhD Student positions available!

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Jan 2020

New Review on Clonal Hematopoiesis (CHIP) published

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Dec 2019

Frankfurt University highlights our latest research

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Nov 2019

Lena published bone marrow alterations in CHIP carriers - congrats!

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Oct 2019

Editorial on NATURE paper about stem cell expansion by Michael

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Oct 2019

Ilaria successfully defended her thesis - congrats Dr. Lunger

Oct 2019

Rene received MD stipent from the JackstƤdt-Stiftung at the DGHO - congrats!

Sept 2019

Our CHIP Team scored again - EHJ publication!

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May 2019

ChristinaĀ´s paper about CHIP after autoSCT published in Cell Reports - congrats!

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Jan 2019

New lab positions available (PhD, Postdoc, TA)

Dec 2018

Clonal hematopoiesis contribute to ischemic heart failure - published in JAMA Cardiology

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Dec 2018

New TA position available

Dec 2018

New Postdoc position available

Nov 2018

Public Report about Rieger Lab

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Sept 2018

Excellence Cluster Cardio-Pulmonary-Institute funded!

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Aug 2018

Michael invited speaker at ISEH 2018 in Los Angeles

June 2018

New PostDoc position available

Feb 2018

MiRNA-193b in AML - great story published in JCO

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Dec 2017

Bartosch successfully defended his thesis - congrats Dr. Wojcik

Dec 2017

Bartosch and Fabian published Perspective Article in ONCOTARGET

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ļ»æ

Research Topics

We focus our research on basic mechanisms that control stem cell fate decisions (self-renewal vs. differentiation, lineage choice, quiescence vs. proliferation). These fate decisions need to be strictly balanced for normal tissue regeneration and for emergency situations, and are dysregulated in diseases (e.g. cancer). We utilize various organ stem cell systems (hematopoietic cells, mammary gland, colon) from mice and humans to unravel molecular and functional clues how these decisions are integrated in normal stemcell biology and how malignant stem cells can be targeted for innovative disease treatment.

  • Intrinsic and extrinsic molecular control of hematopoietic stem cell fate decisions
  • Hematopoietic differentiation hierarchy
  • Identification and characterization of leukemia-initiating (stem) cells
  • The role of miRNAs in hematopoietic and mammary gland stem cell biology and cancer
  • New colon cancer-initiating (stem) cell markers and target molecules for diagnosis and therapy

Image cell fate decisions Hematopoietic stem cell fate decision control

Hematopoiesis

In our body, hematopoietic stem cells continuously generate billions of new blood cells of more than ten specialized blood cell lineages (multipotency) while sustaining their number constant life-long (self-renewal). We investigate the molecular control of these stem cell fate decisions, which are orchestrated by a complicated interplay of extrinsic signals, signal transduction pathways, gene expression regulation and pre- / post-translational influences. Hematopoietic stem cells are rare cells in adult bone marrow and enrichment of these cells by multi-parameter fluorescence-activated cell sorting (FACS) and analyses at the single cell level are essential for understanding their biology in detail. Modern imaging approaches (continuous cell tracking) combined with latest molecular and cellular technologies should elucidate these mechanisms in high sequential resolution at the single cell level during differentiation. Hematopoiesis is a massive regenerative process that is hierarchically organized with the stem cell at the apex of the hierarchy. Marker-defined stem cells and progenitor stages with restricted lineage potential can be prospectively isolated ā€“ from mouse and human origin. However, the hematopoietic hierarchy is far better defined in mice than in humans ā€“ and a better resolution of the heterogenic mixture of human stem and progenitor cells is urgently awaited for improved usage of these valuable cells for cell and gene therapeutic approaches.

Hematopoietic differentiation hierarchy Hematopoietic differentiation hierarchy (from Rieger and Schroeder, Cold Spring Harb Perspect Biol 4:a008250, 2012)
mammary gland wholemount Murine mammary gland wholemount

Mammary gland development

The mammary epithelium is composed of ductal, alveolar, and myoepithelial cells, all can be generated from a single mammary stem cell. As a part of our attempt to reveal the basic mechanism which govern the transition of a single stem cell into a fully functional organ, we are investigating the function of selected genes (coding or non-coding) which may regulate mammary gland stem cells self-renewal and differentiation during the four stages of the mammary developmental cycle (virgin, pregnant, lactating, and involution). Our goal is to develop new approaches that will be based on cutting edge technology that will allow us to evaluate the role of individual genes on mammary gland development as well as their involvement during breast cancer oncogenesis, with the hope to find new regulatory genes serving as potential targets for therapy.

Human
   colonosphereHuman colonosphere

Colon carcinoma-initiating stem cells

Colorectal cancer is the second leading cause of cancer related death. Current knowledge suggests that colon cancer is a stem-cell driven malignancy, in which only a small population of cells, termed as cancer-initiating stem cells (CSCs), are able to initiate and sustain tumor growth. Worthy to mention is that CSCs not necessarily arise only from normal stem cells. Similar to normal stem cells, CSCs have the ability to self-renew and to generate the cellular heterogeneity of the tumor by differentiation. CSCs are thought to be resistant to conventional anticancer therapy and so provoke tumor relapse after treatment. Moreover, CSCs share properties of metastasis-initiating cells. CSCs have been initially identified in acute myeloid leukemia, and subsequently in solid human malignancies. Despite the description of some surface markers, only an insufficient purity of colorectal CSCs can be achieved and their biology remains largely undefined. The link of functional behavior at the single cell level with prospective identification of CSCs by surface markers and in vivo functional read-outs helped to identify a more aggressive colon cancer subpopulation, and determined its molecular composition (proteome) in order to identify new vulnerables for targeted cellular therapies and diagnostic markers.

Technologies:

  • Long-term time-lapse imaging and single cell tracking
  • Multiparameter FACS analyses and cell sorting
  • Multiplex intracellular cytometry for signaling and RNA expression
  • Clonal in vitro differentiation assays (CFU, mammosphere assay, tumorsphere assays)
  • Single cell genomic and transcriptomic analyses
  • Organ reconstitution assays by transplantations (congenic and xenograft)
  • Orthotopic transplantation tumor models

Download:     MP4   /   WebM   /   Ogv

Instructive differentiation of granulocyte-macrophage progenitors(GMPs) in macrophages by the cytokine M-CSF. The lineage-commitment marker LysM::GFP is expressed at the lineage-restricted precursor stage. Every single cell is continuously tracked in the developing macrophage colony (orange dots). (from Rieger et al., Science 325, 2009)

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portrait Michael Rieger

Prof. Dr. Michael Rieger

Curriculum Vitae

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