Research Groups

Portrait Anthony Gavalas

Anthony Gavalas

Cell fate decisions of pancreas progenitor and stem cells

Previous and Current Research

We are interested in understanding how extracellular signals and intrinsic genetic programs interact to dictate cell fate decisions in stem and progenitor cells. The main focus is the development of the endocrine lineage in the pancreas and the conversion of pluripotent stem cells into functional beta cells.

We have modeled two processes of interest, the development of the pancreas endocrine lineage and the specification of a motor neuron population in the mammalian hindbrain using directed differentiation of mouse ES cells and inducible expression of selected transcription factors. 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. 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 a rare population of the adult pancreas. Aldh1b1 elimination during development accelerates differentiation and compromises functionality of the adult beta cells. On the other hand, the rare Aldh1b1 expressing cells, in the adult pancreas, have stem cell features suggesting that this gene mediates self-renewal of pancreas progenitors. Such findings are being exploited for the efficient conversion of human pluripotent stem cells into beta cells.

Anthony Gavalas Research: figure
Figure: Centroacinar cells are specifically by expression of Aldh1b1 (green fluorescence)
Future Projects and Goals
  • Identify distinct signaling requirements for the different pancreatic lineages
  • Isolate and functionally analyze the adult pancreas stem cells
  • Understand the metabolic requirements for the maintenance of pancreas progenitor cells
  • Use directed differentiation of human pluripotent stem cells into beta cells to understand human endocrine development and develop cell therapies for diabetes.
Methodological and Technical Expertise
  • Directed neural differentiation of mouse embryonic stem cells
  • Generation of beta like cells from human pluripotent stem cells
  • Organotypic culture of embryonic pancreas
  • Organoid cultures of embryonic and adult pancreas progenitors
  • All experimental approaches for molecular embryology
Selected Publications

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
PLoS Biology, 15, (e2000949) (2017)

Anastasiou V, Ninou E, Alexopoulou D, Gouti M, Müller A, Dahl A, Solimena M, Serafimidis I, Gavalas A
Aldehyde dehydrogenase activity is necessary for beta cell development and functionality in mice
Diabetologia, 59:139–50 (2016)

Ioannou M, Serafimidis I, Sussel L, Arnes L, Singh S, Vasiliou V, Gavalas A
ALDH1B1 is a potential stem / progenitor marker for multiple pancreas progenitor pools
Dev. Biol. 374:153–63 (2013)

Serafimidis I, Heximer S, Beis D, Gavalas A
GPCR signaling and S1P play a phylogenetically conserved role in endocrine pancreas morphogenesis
Mol. Cell. Biol. 31:5702–11 (2011)

Gouti M, Briscoe J, Gavalas A
Anterior Hox genes interact with components of the neural crest specification network to induce neural crest fates
Stem Cells, 29:858–70 (2011)

CV

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.

Contact

Paul Langerhans Institute Dresden
Center for Regenerative Therapies Dresden
Fetscherstraße 105
01307 Dresden

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