Dr. Gabriele DUva is finishing up his postdoctoral research at the Weizmann Institute. Here is his account of three years of highly successful research on regenerating heart cells after injury. Among other things, it is the story of the way that different ideas from vastly different research areas can, over the dinner table or in casual conversation, provide the inspiration for outstanding research:

Three years ago, when I joined the lab of Prof. Eldad Tzahor, the emerging field of cardiac regeneration was totally obscure to me. My scientific track at that time was mainly focused on normal and cancer stem cells: cells that build our bodies during development and adulthood. The deregulation of these cells can lead to cancer. I have to admit that I didnt know even the shape of a cardiac cell when my postdoc journey started

Eldads lab was also switching fields well, not drastically, like me, but still it was a transition from a basic research on the development of the heart to the challenge of heart regeneration during adult life.

Two neonatal cardiomyocytes (staining in red) undergoing cell division after treatment with NRG1

In contrast to most tissues in our body, which renew themselves throughout life using our pools of stem cells, the renewal of heart cells in adulthood is extremely low; it almost doesnt exist. Just to give an approximate picture of renewal and regeneration processes: Every day we produce billions of new blood cells that completely replace the old ones in a few months. In contrast, heart cells renewal is so low that, many cardiac cells remain with us for our entire life, from birth to death! Consequently, heart injuries cannot be truly repaired, leading to (often lethal) cardiovascular diseases. This might appear somewhat nonsensical, since the heart is our most vital organ: No (heart) beat no life.

Hence a challenge for many scientists is to understand how to induce heart regeneration Scientists have been trying different strategies, for example, the injection of stem cells. We decided to adopt a different strategy one that mimics the natural regenerative process of healing the heart in such regenerative organisms as amphibians and fish, and even newly-born mice. In all these cases the regeneration of the heart involves the proliferation of heart muscle cells called cardiomyocytes. Therefore the challenge before us was: How can we push cardiomyocytes to divide?

We adopted a team strategy. Cancer turned out to be a somewhat useful model for a strategy. After all, the hallmark of this disease is continuous self-renewal and cell proliferation. Starting from this thought, Prof. Yossi Yarden, a leading expert in the cancer field, suggested: Why dont you try an oncogene, such as ERBB2, whose deregulation can lead to uncontrolled cellular growth and tumour development? The idea was that cardiomyocytes could be pushed into a proliferative state by this cancer-promoting agent. To Eldad, this was a nice life circle closing, since Eldad, when he was a PhD student in Yossis lab, focused exactly on the ERBB2 mechanism of action in cancer progression. I must admit, the idea sounded very intriguing and I really liked it.

Eldad, as a developmental biologist, had a different approach. Based on his field of expertise, his tactic was to apply proliferative (and regenerative) strategies learned from the embryos, when heart cells normally proliferate to form a functional organ. It turned out that a key player in driving embryonic heart growth is again ERBB2!

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Guest post: Dr. Gabriele DUva: How to Grow New Heart Cells [The Weizmann Wave]