Olov Andersson's Group

Bridging developmental biology and drug discovery, we use the zebrafish model to elucidate organogenesis and related mechanisms of disease.

We are currently focusing on pancreatic beta-cell regeneration. Increasing the number of insulin-producing beta-cells might prove a better treatment for diabetes, which is at present controlled but not cured by insulin injections. Diabetes is characterized by elevated blood glucose levels, a consequence of insufficient insulin supply and/or insulin resistance. Despite mechanistic differences, both type 1 and late-stage type 2 diabetes feature depletion of beta-cells. Experimental ablation of beta-cells by chemical treatment or partial pancreatectomy in zebrafish and rodents is followed by significant recovery of the beta-cell mass, indicating that the pancreas has the capacity to regenerate. This regenerative capacity could potentially be exploited therapeutically - if the underlying mechanisms were better understood.

A microscopic image picture of a zebrafish embryo's pancreas
By three days after fertilization, the zebrafish has already developed a pancreas (exocrine pancreas shown in green; endocrine pancreas shown in red), liver and gut tube (both shown in white).

We perform unbiased chemical-genetic screens in zebrafish to identify compounds, signals and cellular mechanisms that promote beta-cell regeneration. The zebrafish model is particularly good for studying pancreatic development in vivo. First, the simplicity of its organ structures (e.g. the zebrafish embryo has only one pancreatic islet during the first week of development) allows rapid analysis of cellular changes. Second, zebrafish embryos are amenable to efficient transgenesis and drug delivery.

 

By using a wide range of techniques, we are investigating three different cellular mechanisms of beta-cell regeneration:

  • Induction of beta-cell neogenesis
  • Promotion of beta-cell proliferation
  • Generation of ectopic insulin-producing cells

In sum, we aim to identify and characterize compounds, signalling pathways and cellular mechanisms that can induce or increase beta-cell regeneration, with the overarching goal of developing new therapies for diabetes.

Group Members

Collage of portraits.

 

Group Members
Olov Andersson Associate Professor/Principal Investigator
Lorenzo Buttò PhD student
Jeremie Charbord Research Specialist
Lian Chu Research Specialist
Daniel Colquhoun Postdoctoral researcher
Sophie Kipper Master student
Ka-Cheuk Liu Research Specialist
Kyle Mamounis Postdoctoral researcher
Jiarui Mi PhD student
Lipeng Ren PhD student

Selected Publications

Efficient knock-in method enabling lineage tracing in zebrafish.
Mi J, Andersson O
Life Sci Alliance 2023 May;6(5):

In vivo drug discovery for increasing incretin-expressing cells identifies DYRK inhibitors that reinforce the enteroendocrine system.
Chu L, Terasaki M, Mattsson CL, Teinturier R, Charbord J, Dirice E, Liu KC, Miskelly MG, Zhou Q, Wierup N, Kulkarni RN, Andersson O
Cell Chem Biol 2022 Aug;():

MNK2 deficiency potentiates β-cell regeneration via translational regulation.
Karampelias C, Watt K, Mattsson CL, Ruiz ÁF, Rezanejad H, Mi J, Liu X, Chu L, Locasale JW, Korbutt GS, Rovira M, Larsson O, Andersson O
Nat Chem Biol 2022 Jun;():

Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification.
Liu KC, Villasenor A, Bertuzzi M, Schmitner N, Radros N, Rautio L, Mattonet K, Matsuoka RL, Reischauer S, Stainier DY, Andersson O
Elife 2021 Aug;10():

Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation
Karampelias C, Rezanejad H, Rosko M, Duan L, Lu J, Pazzagli L, Bertolino P, Cesta CE, Liu X, Korbutt GS, Andersson O
Nature Communications volume 12, Article number: 3362 (2021)

In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR.
Charbord J, Ren L, Sharma RB, Johansson A, Ågren R, Chu L, Tworus D, Schulz N, Charbord P, Stewart AF, Wang P, Alonso LC, Andersson O
Nat Metab 2021 May;3(5):682-700

Linda Lindell
31-05-2023