Elly Tanaka

Home
Discover
Discoveries
Elly Tanaka

Regrowing arms, legs, or even parts of the heart – what is impossible for us humans comes easily to the axolotl. Molecular biologist Elly Tanaka is researching the molecular basis of these amazing abilities and has discovered key principles of regeneration. Her findings provide insights into how human cells could one day replace lost tissue.

When several trucks pulled up in front of the Vienna BioCenter in 2016, it quickly became clear that this was no ordinary delivery. They were bringing hundreds of water tanks full of axolotls, the mysterious salamanders that can regenerate arms, legs, spinal tissue, and even parts of the heart after an injury. Joining them was molecular biologist Elly Tanaka, coming from Dresden to work initially at the Research Institute of Molecular Pathology (IMP). “These animals are not only the model system I work with, they are the key to a fundamental question of biology: Why can axolotls regrow body parts and we humans can’t?” says Elly Tanaka.

This question is centuries old: Way back in 1768, the Italian naturalist Lazzaro Spallanzani observed that the legs and tails of salamanders grow back after an injury. Since the mid-19th century, scientists have been working on the question of how exactly this regeneration takes place. During the interwar period, when experimental developmental biology was at its peak, the axolotl and its regeneration abilities were also the subject of intensive research. However, systematic research remained problematic for a long time, as the animals were difficult to keep and slow to reproduce. Later on, researchers lacked genetic tools.

In a nutshell

Elly Tanaka decoded central principles of regeneration with the axolotl. She discovered the long-sought-after positional memory, which enables cells in the arm and leg to know which part they need to renew. At the same time, her team is researching how the axolotl’s brain and heart become functional again after injury. Tanaka’s work is clearing the way for a deeper understanding of regeneration and to new perspectives for medicine.

Elly Tanaka holding her Science Award in front of a green area in the arcade courtyard of City Hall — Elly Tanaka is a leading international expert on the regeneration of complex bodily structures. She was presented with the 2025 FWF Wittgenstein Award for her groundbreaking findings. © FWF/Der Knopfdrücker

Portrait of an axolotl on black background — Regrowing arms, legs, or even parts of the heart – what is impossible for us humans comes easily to the axolotl. © IMP/IMBA

Early stages and initial methods

When Elly Tanaka became interested in regenerative biology in the late 1990s, the field was considered outdated. But that was an incentive for Tanaka. “There were many unanswered questions, but hardly anyone was still working on them,” she says. She saw an opportunity to make the axolotl accessible for research using molecular biology tools that were already in use for other model organisms such as flies and mice, but not yet for the axolotl.

During her doctorate, Tanaka investigated how nerve cells wire themselves in frog embryos. Frog embryos were known to have a puzzling characteristic: If a single cell is removed from the early embryo, a whole frog can develop from that individual cell. “I have always been fascinated by how a single part of an animal can contain the information to build an entire organism or replace a missing part,” she says.

Her postdoc studies with Jeremy Brockes in London then led her to focus on regeneration, albeit under difficult conditions. The laboratory had the resources to carry out regeneration experiments on one species of salamander, but there was no way of establishing stable colonies of this species or genetically manipulating the animals. “My lab colleagues went out and caught the salamanders for their research in the wild,” recalls Tanaka. “To be honest, that was too tedious and time-consuming for me, so I worked on cell cultures, not on animals.”

This logistical problem led to her groundbreaking decision: In her first own laboratory in Dresden, which she started in 1999, Tanaka relied on the axolotl. Rather than relying on wild salamanders, she sourced animals for her laboratory from an axolotl colony established in the USA in the 1950s. Other laboratories also worked with the axolotl. Researchers had already carried out traditional regeneration experiments with the animals, and their shorter generation time was better suited for genetic manipulation.

Tanaka's first project: the regeneration of the tail. Axolotl tails are flat, allowing for live imaging and microscopic examinations on living animals, a method she brought with her from her time as a PhD candidate. Together, Tanaka and her own first PhD student, Karen Echeverri, began to experiment – and above all to improvise. They wanted to observe which cells in the regenerating tail contributed to regeneration and how they did it.

Short bio

Elly Tanaka has headed the IMBA – Institute of Molecular Biotechnology of the Austrian Academy of Sciences since 2024. From 2016 to 2024, she was a group head at the neighboring Research Institute of Molecular Pathology (IMP) at the Vienna BioCenter. Before coming to Vienna, Elly Tanaka was a researcher at the DFG Center for Regenerative Therapies at Dresden University of Technology from 2008 to 2016, where she was director from 2014 to 2016. In 1999, she founded her first laboratory at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, where she conducted research until 2008. Tanaka’s research awards include the Ernst Schering Prize, the Erwin Schrödinger Award, the FEBS EMBO Women in Science Award, and the Schleiden Medal, as well as two Advanced Grants and a Synergy Grant from the European Research Council ERC. She is an elected member of the US National Academy of Sciences and a full member of the Austrian Academy of Sciences. The FWF has supported Tanaka's research since her arrival in Vienna, and she also received the FWF Wittgenstein Award in 2025.

“I have always been fascinated by how a single part of an animal can contain the information to build an entire organism or replace a missing part”

Initially, the researchers introduced dyes into muscle cells, but at the time, methods involving a green fluorescent protein known as GFP as a marker for certain structures or genes were beginning to emerge. In improvised experiments, they attached razor blades to an electrophoresis device, introducing GFP into spinal cord cells for the first time. This enabled them to track how cells behave during regeneration over longer periods of time. “We have refined this technique over time and still use it to study spinal cord regeneration,” explains Tanaka.

The reactions to her work were mixed. Some thought it was revolutionary to track cells during regeneration, others criticized it as too descriptive. “There were people who immediately wanted to find the one molecule that drives regeneration. They thought it was boring that we were ‘just observing cells’.” Tanaka, however, remained true to her approach. “There will always be doubters. But to understand the mechanisms of regeneration, you first have to understand what happens during regeneration.”

Although Tanaka initially investigated tail regeneration for the sake of simplicity, she could not escape the fascination of arm and leg regeneration for long. “Arms and legs are canonical places to study regeneration, many traditional experiments have been conducted on these limbs. Once Karen Echeverri got the electroporation working in the spinal cord, she applied the technique to the arms and legs to understand which cell types contribute to regeneration there.”

Check this out on scilog

The Miraculous Cell Memory of the Axolotl

Genomics and new technologies

At the same time, the laboratory began expanding its molecular toolbox for the axolotl. “Excellent people in my lab drove this work. Ji-Feng Fei, who now runs his own laboratory in China, had a wonderful talent for developing genome engineering methods for the axolotl.” From classic mammalian methods such as TALENs to the then brand new CRISPR/Cas9 gene scissors, he developed ways to specifically modify the axolotl genome.

But for a long time, axolotl research faced an almost insurmountable hurdle: The genome of the axolotl, which is about 10 times larger than that of humans, had not been fully sequenced. Without full knowledge of the “genome text,” it is difficult to edit it. With colleagues in Dresden, the Tanaka group set to work decoding the seemingly endless axolotl genome. This is no easy task, because the axolotl genome is full of constantly repeating sections, like a giant jigsaw puzzle in which many pieces look almost identical. Sorting this data was so complex that bioinformaticians first had to develop new methods to accomplish this task. The triumph came in 2018, when the complete genome was finally available. “That gave us what we needed to precisely edit the axolotl genome,” says Tanaka.

At the same time, thanks to the complete genome, it became clear how chromatin changes and histone marks control regeneration. “In 2024, we published findings based on genome sequencing, showing that the chromatin in cells at different parts of the leg is different even before regeneration: This chromatin structure acts as a zip code that tells the cells where they are and which arm or leg structure they should regrow.”

With the new focus on the genome and genome editing, the decision was made to relocate to Vienna. “While the focus in Dresden was on cell biology, the focus in Vienna was on genomics – and this gave us the perfect environment to use genomics to gain a deeper understanding of regeneration. Although we had already developed transgenic axolotl lines in Dresden, this work really picked up speed when we moved to Vienna: We now have over 300 transgenic axolotl lines in our colony to study different areas of regeneration.”

Elly Tanaka heads the IMBA – Institute of Molecular Biotechnology of the Austrian Academy of Sciences. Tanaka's scientific awards include the Ernst Schering Prize, the Erwin Schrödinger Award, and the Schleiden Medal, as well as two Advanced Grants and a Synergy Grant from the ERC. The FWF has supported Tanaka’s research since her arrival in Vienna.

Breakthroughs

Tanaka and her research group have achieved a number of breakthroughs thanks to the new methods. First of all, in 2009 they were able to clarify a key question of regeneration: where the regenerating cells come from in the first place. In the axolotl, wounds first develop a layer of cells, the blastema, and only then does the new arm or leg form. But which cells make up the blastema?

An earlier assumption was that cells must completely reprogram themselves to an embryonic state in order to form a new body part. However, Tanaka’s research has shown that most cells retain their original identity during regeneration – muscle stays muscle, bone stays bone. That realization made it clear that axolotl regeneration is not based on the principle of complete “reprogramming.”

The next major step in 2018 was to identify the actual cells behind the construction plan. Tanaka succeeded for the first time in showing that within a radius of 500 micrometers of the injury, a group of connective tissue cells, the fibroblasts, lose all their cell properties and build up the blastema. “We were able to show for the first time using molecular biology that there are no ‘reserved’ stem cells in the axolotl’s arms and legs that are just standing by, waiting to contribute to tissue regeneration after an injury.”

This finding was also important in the context of mammalian regeneration, such as in humans: If the axolotl used specialized stem cells for regeneration, which are not present in mammals, this mechanism would not be an option for humans. But Tanaka went on to compare the axolotl with frogs, because unlike the axolotl, the adult frog cannot regenerate after injury. “We wanted to find out whether this is because the key cells – the fibroblasts – do not fully dedifferentiate in frogs,” explains Tanaka. This was indeed the case. “This is interesting, because now we want to understand how we can get mammalian cells – which also fail to dedifferentiate – to manage this step.”

But one crucial question remained: How do the cells know which part of the body to rebuild? If the axolotl loses its arm at the shoulder, the entire arm grows back, but if it loses just a hand, only the hand grows back. The answer lies in the epigenetic signature of the fibroblasts: Chromatin patterns reveal their position in the body, as Tanaka and her team were able to show in 2024.

Finally, in 2025, the team made one of its most important discoveries: how cells “remember” their position. The Hand2 gene plays a key role. This gene is active on the side of the arm or leg where the little finger grows back. After an injury, Hand2 ramps up regeneration: It activates signals on the thumb side and the little finger side, which instruct the cells how to grow and shape the reconstructed arms and legs.

Surprisingly, Hand2 is not only temporary: It is already active at a low level in the connective tissue cells of the back half of the arm or leg before an injury, but not on the front side, and thus forms the long sought-after positional memory.

Elly Tanaka in the laboratory behind a terrarium with an axolotl — New perspectives for medicine: Elly Tanaka decoded key principles of regeneration using the axolotl. © Johannes Hloch

Present and future

Today, Tanaka's laboratory not only examines arms and legs, but also many other organs. The liver, heart, brain, and retina are being researched using over 300 transgenic lines. This expansion of her research was also made possible by funding from the FWF. Most recently, Elly Tanaka received the 2025 FWF Wittgenstein Award.

“We are particularly interested in the question of cell competence,” explains Tanaka. “What enables a differentiated cell to regenerate?” In the leg, her group was able to show that fibroblasts become stem cells. In the heart, on the other hand, they were able to prove that heart muscle cells – which were long thought to be unable to divide in adult animals – begin to divide again after an injury. This realization is of major signifigance for humans: After a heart attack, large quantities of heart cells die, and the affected tissue permanently loses function. The team now wants to decode the signals that drive and control heart regeneration.

The Tanaka group is also investigating how nerve cells in the retina react to injuries and how this ability changes with age. The team has already succeeded in differentiating human embryonic stem cells into retinal tissue, specifically into the pigment epithelium of the retina. With the help of this tissue, they are looking for active substances that can be used to repair defects in the pigment epithelium that lead to blindness if left untreated.

At the same time, the group is devoting itself to another neuroscientific focus: the regeneration of the brain. Today, her lab adapts state-of-the-art methods from neuroscience, such as whole brain imaging, to understand how neuronal circuits in the axolotl rewire after an injury, and whether behavior is truly restored afterwards.

Tanaka is also concerned with another fundamental question: How does the adult animal manage to coordinate the right signals over such large amounts of tissue and distances? “In the embryo, these signals act in small structures, in the adult everything is much larger. How does that work?” The first indications come from Tanaka's original area, the regeneration of the tail. When an adult axolotl loses its tail, it regenerates a complete set of vertebrae whose size is precisely adapted to the size of the adult animal. The axolotl uses completely different mechanisms for this than during embryonic development. “But how does the tissue determine the correct size?”

The answer to this question has direct implications for regenerative medicine: Once we understand these principles, they could be applied to human stem cells and organoids could be developed to serve as models for regenerative medicine.

When Tanaka began her research, she hadn’t really thought of medical applications. “I was interested in the understanding how it worked – and I still am.” Today, however, it is becoming increasingly clear how important her work could be for medicine. “We want to grow organoids and use them to research the regeneration of the arm and leg in the human system and ideally influence it in a targeted way.”

Improvised experiments with razor blades and dyes gave rise to modern regeneration research. The axolotl, an unusual animal, has become a model that is changing not only our understanding of itself but perhaps one day also human medicine.