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β-cell biology and regeneration - Nikolay Ninov

The pancreatic β-cells are the key metabolic sensors and effectors for insulin release, which is the only hormone known to lower blood glucose concentrations. Type 1 diabetes mellitus is an autoimmune disease characterized by the destruction of beta-cells in the pancreatic islets, leading to insulin deficiency and hyperglycemia.  In contrast, type 2 diabetes commences with insulin resistance followed by beta cell loss and hyperglycemia.  Restoring functional β-cell mass is recognized as a promising therapeutic avenue towards normalizing glycemic control in both type 1 and 2 diabetics.  Thus, our research goal is to understand the molecular and cellular events required for pancreatic β-cell regeneration, and apply this knowledge towards the development of cell replacement therapies for diabetes.

Previous and current research

The goal of our group is to identify new signaling pathways and drugs that enhance endogenous beta-cell regeneration. Using a set of novel transgenic reporter zebrafish lines, which monitor beta-cell proliferation in the living animal, we have performed the first in vivo high-content chemical screen for inducers of beta-cell proliferation, which identified FDA-approved drugs and natural products that expand beta-cell mass. more

Future projects and goals

  • High content in vivo drug screens for inducers of pancreatic β-cell differentiation and replication.
  • Metabolic control of β-cell proliferation.
  • Notch signaling in pancreatic stem cell differentiation and renewal.
  • Novel (drug) targets for pancreatic stem cell activation and differentiation into β-cells.

Group leader

Selected publications

Janjuha S*., Singh SP*., Tsakmaki A., Gharavy NM., Murawala P., Konantz J., Birke S., Hodson D., Rutter G., Bewick G., and Ninov N. Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish. eLIFE (2018), doi: 10.7554/eLife.32965

Spanjaard B.; Hu B.; Mitic N.; Olivares-Chauvet P.; Janjuha S.; Ninov N.; Junker J.P.; Simultaneous lineage tracing and cell type identification using CRISPR/Cas9 induced genetic scars Nature Biotechnology (2018), doi: 10.1038/nbt.4124

Singh SP, Janjuha S, Hartmann T, Kayısoglu O, Konantz J, Birke S, Murawala P, Alfar EA, Murata K, Eugster A, Tsuji N, Morrissey E, Brand M, and Ninov N. Different developmental histories of beta-cells generate functional and proliferative heterogeneity during islet growth. Nature Communications (2017). DOI : 10.1038/s41467-017-00461-3.

Alfar EA, Kirova D, Konantz J, Birke S, Mansfeld J, and Ninov N. Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity. Scientific Reports (2017) 7(1):3994. doi: 10.1038/s41598-017-03873-9.

Kamel M and Ninov N. Catching new targets in metabolic disease with a zebrafish (2017). Current Opinion in Pharmacology. doi.org/10.1016/j.coph.2017.08.007

Singh, SP and Ninov, N. The triumvirate of beta-cell regeneration: Solutions and bottlenecks to curing diabetes. International Journal of Developmental Biology (in press)

Janjuha S*., Singh SP*, and Ninov N. Analysis of Beta-cell Function Using Single-cell Resolution Calcium Imaging in Zebrafish Islets. JoVE (in press)

Contact

Group Leader

Dr. Nikolay Ninov
nikolay.ninov[at]crt-dresden.de


Assistant to Group Leader

Silvia Palme
silvia.palme[at]crt-dresden.de
Phone: +49 (0)351 458 82104

FUNDING