Exploring Regeneration

Nature has always captivated Henri Jasper. As a child, he followed tropical ants in Ecuador, watching them cut and carry leaves back to their colonies, sometimes collecting them for observation before setting them free.

“It was one of those things I could spend afternoons on, trying to follow their path. That’s where my interest in the natural world started,” says Henri, Principal Fellow, Regenerative Medicine.

After spending his childhood in Ecuador and Peru, Henri returned to his native Germany to attend university, where he studied developmental biology, first in frogs as an undergraduate at the University of Tübingen and then in fruit flies as a Ph.D. student at the University of Heidelberg.

The same pathways that influence a cell’s development also control how cells respond to stress in adult organisms, he says. Studying these common pathways eventually led Henri toward an interest in aging. If he could change how cells respond to stress, perhaps he could help fruit flies—and, potentially, humans—live better and longer.

Model Organisms

Though he started his Ph.D. in Germany, Henri finished it at the University of Rochester in New York, having followed his advisor across the Atlantic. There, and later at the Buck Institute in California, he explored how regulating pathways, such as insulin signaling, could influence a fly’s longevity.

“Early on, we found a genetic condition associated with extended lifespan in flies. The key gene involved in this condition interacted with the insulin signaling pathway, which was known to play an important role in aging. This led us to explore the role of the insulin signaling pathway in controlling stress response, stress tolerance, the health of the animal, and, accordingly, longevity,” Henri says. “Because of that work, I got more and more involved in the aging field, which was really exploding at the time.”

But Henri soon found himself at a crossroads. He could either continue studying flies, or switch to worms, which were the standard model organism for aging research at the time. That is because experiments in longevity were much faster to do in worms than in flies. Even though it risked Henri’s competitive advantage in the field, he stuck with flies because he saw a path towards using them to study the fundamental processes behind aging and tissue maintenance.

He was particularly interested in how their intestines regenerate, a process that also happens in humans. He and his team began probing the role of specific genes and pathways in regulating the activity of stem cells, which have the unique potential to develop into many different types of cells. In the intestine, these cells are constantly developing into cells that make up the intestinal wall, playing a key role in the regeneration of the intestine. However, aging impacts the capacity of these cells to regenerate the intestine, ultimately limiting lifespan.

“It was a great entry point to start exploring how aging impacts such regenerative processes more broadly,” he says.

Henri’s next step took him to industry, where he sought to translate his work in flies to models for human disease, ultimately aiming to target a range of degenerative age-related diseases. “Moving to Genentech allowed me to ask new questions and explore how stem cells can be manipulated to improve how tissues function. It also provided opportunities to translate our research to vertebrates, and use those insights to ultimately try to help people.”

Coaxing Cells

At Genentech, Henri is pursuing regenerative approaches that may restore function in diseased tissue rather than just preventing more damage.

“That’s what many current medicines do—you have a disease and you try to slow it down, be it cancer or inflammatory disease,” he says. “With age-related macular degeneration [AMD] in the eye, for example, current therapies only slow down the progression of the disease. There is no restoration of vision once you have lost it.”

Henri and his team are using regenerative medicine to ask new questions. Can we restore vision in patients with AMD? Can we bring back heart function after a heart attack? Can we regenerate skin after it is burned?

Understanding how our cells lose the ability to regenerate as we age may inform Henri’s team as they seek to develop new therapeutic approaches for chronic and aging-related diseases. Henri notes that these diseases “are a consequence of long-term inflammatory processes, defective wound healing, and, very clearly, impaired stem cell function.”

His main focus is coaxing stem cells inside the patient’s body to become cells that repair diseased tissue. The eye is a natural target for this approach, thanks to what scientists have learned from other animals.

“There are amphibians, fish and birds that can repair the retina by activating a specific type of stem cell called the Müller glial cell,” Henri says. “Mammals have lost the capacity to regenerate the retina, but they still have these Müller glial cells.”

The hope is to restore vision in mammals by identifying and delivering the right proteins to these stem cells to coax them into becoming functional cells, like photoreceptors, or cells in the eye’s retina that convert light into signals that are sent to the brain and are important for our color vision and night vision.

FROM FLY GENETICS TO HUMAN AGING: INSIGHTS INTO REGENERATIVE MEDICINE

Listen to Henri discuss how model organisms can help us understand ways to delay the onset of disease or engage repair mechanisms once a disease has arisen.

Cultivating Passion and Ownership

As he advances his work at Genentech, Henri is helping the next generation of scientists come into their own. He’s passing on what he learned from his own mentors and role models, including his Ph.D. mentor from the University of Rochester.

“Dirk Bohmann taught me that being a good leader and mentor means allowing people to follow their scientific curiosity while providing the right support when they need it,” says Henri. “I try to emulate this in my lab by giving people a sense of ownership and responsibility for their work, while ensuring that they define their questions clearly and design the best experiments to test their ideas. Ultimately, the most important thing is for everyone in the lab to be passionate and excited about discovery.”

Henri notes that Genentech’s culture of embracing curiosity and collaboration has and will continue to play an important role in this field. It isn’t an easy process to translate the basic research into potential new therapies, but as Henri notes, Genentech is a place “where people truly are encouraged to explore their scientific questions, eager to lead new projects and collaborate closely with diverse disciplines in order to make things happen.”

Extending Health

Thanks to discoveries at Genentech and beyond, aging research has made leaps and bounds over the last decade. As with any rapidly evolving field, however, there will likely be setbacks down the road. “You can imagine that the next decade is going to have a lot of failures. But the potential for revolutionary new treatments is immense,” Henri says.

More and more regenerative treatments are entering or approaching clinical trials, including cell therapies for diseases of the retina and lung, and gene therapies that reprogram cells inside the heart or pancreas. This research could help identify strategies to restore organ function for people with a wide range of illnesses.

“It’s a different paradigm for medicine. One that revolves around tissue rejuvenation and lifespan extension. But most importantly, it aspires to allow patients to live healthy lives for longer,” Henri says.



Henri Jasper is a Principal Fellow, Regenerative Medicine at Genentech. Learn more about his work here.