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Portrait Anthony Gavalas

© CRTD

We are interested in understanding how extracellular signals and intrinsic genetic programs interact to initially dictate cell fate decisions in stem and progenitor cells and eventually establish mature phenotypes. Our main focus is the development of the endocrine lineage in the pancreas and the conversion of human pluripotent stem cells into functional beta cells. Key questions that we are addressing concern the signals that guide cell transitions during pancreas differentiation and the regulators of the timing of these transitions.

We have identified a new signal, sphingosine-1-phosphate, which plays a conserved role in the aggregation of endocrine cells to form islets. The same signaling pathway mediates survival of acinar and endocrine progenitors and triggers their differentiation through stabilization of YAP and attenuation of Notch signaling. Extending these findings, we have found that effectors of GPCR signaling regulate lineage allocation during pancreas development.

Additionally, we have found that Aldh1b1, encoding a mitochondrial enzyme, regulates the timing of differentiation in the developing pancreas. The gene is expressed in all pancreatic progenitors during development and in the rare centroacinar cells of the adult pancreas but not in differentiated pancreatic cells. Aldh1b1 elimination during development accelerated differentiation and compromised functionality of the adult beta cells. Recent findings suggest that Aldh1b1 is a metabolic regulator that helps determine chromatin accessibility. Genetic lineage tracing showed that the rare Aldh1b1 expressing cells in the adult pancreas give rise to cells of all three pancreatic lineages during homeostasis. Strikingly, we have found that Aldh1b1 expressing cells are enriched in Kras expression and that Aldh1b1 is required for the development of pancreatic cancer suggesting that these cells might be cancer initiating cells.

Finally, we are taking advantage of these findings to expand in culture pancreatic progenitors derived from human pluripotent stem cells and efficiently convert them into pancreatic islets containing mature beta cells.

Anthony Gavalas Research: Figure
Figure: Centroacinar cells are specifically by expression of Aldh1b1 (green fluorescence)

Future Projects and Goals

  • Identify signaling requirements and the underlying molecular mechanisms for the different pancreatic lineages
  • Explore the role of adult pancreas progenitor cells in cancer development
  • Elucidate the role of metabolism in the differentiation of pancreatic progenitors and beta cell functionality
  • Use directed differentiation of human pluripotent stem cells into pancreatic islets to understand human endocrine development and develop cell therapies for diabetes

Methodological and Technical Expertise

  • Generation of pancreatic islet mini-organs from human pluripotent stem cells
  • Organotypic culture of embryonic pancreas
  • Organoid cultures of embryonic and adult pancreas progenitors
  • All experimental approaches for molecular embryology including genetics, genotyping and immunofluorescence
  • Molecular analyses including flow cytometry, RNA-Seq, ATAC-Seq and qPCR

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Anthony Gavalas is currently offering PhD positions

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Open Project
  • Pancreatic islet mini organs for diabetes cell therapy
    Preferred Course of Study/Expertise of Candidate: Molecular biology and imaging, experience with human pluripotent stem cells

Anthony Gavalas is a PI in the International Research Training Group 2251 “Immunological and Cellular Strategies in Metabolic Disease”, which offers a new training programme combining the expertise of TU Dresden and King’s College London and benefits from the transCampus partnership. Via this programme, it is possible to attain a Ph.D. jointly awarded by TU Dresden and King’s College London. Learn more about it on the TU Dresden website.

CV

since 2020
Professor, TU Dresden Medical School, Dresden, Germany

since 2012
Research Group Leader, PLID/CRTD, Dresden, Germany

2012
Research Group Leader/Associate Professor, BRFAA, Athens, Greece

2003–2011
Research Group Leader/Assistant Professor, BRFAA, Athens, Greece

2002–2003
Welcome Trust Career Development Fellow, King’s College, London, U.K.

1999–2001
Post Doctoral Fellow, NIMR, London, U.K.

1994–1998
Post Doctoral Fellow, IGBMC, Illkirch, France

1994
Ph.D. in Biochemistry and Molecular Biology, Purdue University, U.S.A.

More Information

TUD/PLID website

Selected Publications

Pazur K, Giannios I, Lesche M, Rodriguez-Aznar E, Gavalas A
Hoxb1 regulates distinct signaling pathways in neuromesodermal and hindbrain progenitors to promote cell survival and specification
Stem Cells, 40, 175–189 (2022)

Mameishvili E, Serafimidis I, Iwaszkiewicz S, Lesche M, Reinhardt S, Bölicke N, Büttner M, Stellas D, Papadimitropoulou A, Szabolcs M, Anastassiadis K, Dahl A, Theis F, Efstratiadis A, Gavalas A
Aldh1b1 expression defines progenitor cells in the adult pancreas and is required for K-ras induced pancreatic cancer
PNAS, 116, 20679–20688 (2019)

Giannios I, Serafimidis I, Anastasiou V, Pezzola D, Lesche M, Andree C, Bickle M, Gavalas A
Protein methyltransferase inhibition decreases endocrine specification through the upregulation of Aldh1b1 expression
Stem Cells, 37, 640–651 (2019)

Serafimidis I, Rodriguez-Aznar E, Lesche M, Yoshioka K, Takuwa Y, Dahl A, Pan D, Gavalas A
Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signaling
PLOS Biology, 15, e2000949 (2017)

Anastasiou V, Ninou E, Alexopoulou D, Stertmann J, Müller A, Dahl A, Solimena M, Speier S, Serafimidis I, Gavalas A
Aldehyde dehydrogenase activity is necessary for β cell development and functionality
Diabetologia, 59, 139–50 (2016)

Contact

DZD / Paul Langerhans Institute Dresden of Helmholtz Center Munich

Faculty of Medicine, Technische Universität Dresden

Postal address Fetscherstrasse 74

Visitor address Tatzberg 47/49
01307 Dresden