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The Otsuki group investigates how complex vertebrate tissues – such as limbs and jaws – can be regenerated.
What kind of cells do we need for regeneration? How many, and in which combinations? What are the molecular mechanisms that ensure that a regenerated tissue has the correct size, shape and function?
To answer these types of questions, we study a highly regenerative salamander species called the axolotl – one of the only four-legged vertebrates able to regenerate tissues as diverse as skeleton, nervous system and internal organs. We de-construct the regeneration process in vivo using top-down methods such as -omics tools, genetics, and live imaging. Reciprocally, we construct tissues from the ground up by engineering the regenerative principles that we discover into cells in vitro. Uncovering regenerative principles in the axolotl could help identify and overcome roadblocks to regeneration in humans.
To identify cells important for regeneration, we make use of genetic reporters that light up specific groups of cells in the living tissue. This illumination allows us to track cells under the microscope and determine their contributions to the regenerated tissue in time and space. We can selectively profile the illuminated cells to identify the genes that they express and the mechanisms that support their functions.
We use -omics approaches to decode the gene regulation mechanisms that underlie regeneration. Targeting these mechanisms can allow us to control and reprogram the functions of regenerative cells.
For example, we recently discovered that a transcription factor called Hand2 is responsible for ‘little finger-side’ (posterior) identity in the axolotl limb. We found that treating ‘thumb-side’ (anterior) cells with a molecule called Shh forced them to switch on Hand2 and switch over to a posterior identity, thereby changing their functions during regeneration.
The lessons that we learn from studying regeneration in vivo can act as stepping stones towards building tissues in vitro. We are creating 3D assemblies of axolotl cells – called spheroids – that serve as a platform to explore the potential of regenerative cells for tissue engineering.
All research is conducted in accordance with national and EU ethical regulations, with a commitment to welfare and the 3Rs principles.
Otsuki L, Plattner SA, Taniguchi-Sugiura Y, Falcon F, Tanaka EM
Download|2025
Arbanas L I, Cura Costa E, Chara O, Otsuki L, & Tanaka EM
Download|2024
Cura Costa E*, Otsuki L*, Rodrigo Albors A, Tanaka EM, Chara O
Download|2021
Leo Otsuki is a developmental biologist with a background in genetics. He carried out his PhD with Prof. Andrea Brand (University of Cambridge, UK) studying neural stem cell quiescence in Drosophila melanogaster. For his postdoctoral research, he joined the group of Prof. Elly Tanaka (IMBA Vienna, Austria), where he pursued his interest in stem cell regulation in the context of vertebrate limb and spinal cord regeneration. He established his group at the Hubrecht Institute in 2025. His group studies the molecular principles of tissue regeneration in the axolotl, with the aim of applying this knowledge to construct and pattern complex tissues.
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We are seeking a motivated PhD student to develop a 3D axolotl limb cell culture system to study regenerative programs and tissue patterning. The project will use transgenically labelled axolotl cells (see Otsuki et al. 2025) to build an in vitro system that can be used to study interactions among regenerative cells and assemble them into 3D tissues.
This fully funded position is part of the DRIVE-RM regenerative medicine consortium (https://drive-rm.nl/talent-development-program/) and applications should be submitted through the Hubrecht International PhD Program (https://www.hubrecht.eu/hipp/). Applications are open until 15th September 2025, with an expected starting date in Spring 2026.
Previous experience with model organisms and/or with cell culture is highly desirable. Please note that you must have studied biology, or biological study modules, in order to work with animals in the Netherlands. If in doubt, please contact Leo in advance.
