Interview with Buck Professor Dr. Henri Jasper: Stem cells and aging, lessons from Drosophila

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Research Background

Dr. Heinrich (Henri) Jasper is a German-American biologist and Professor at the Buck Institute. He received his BS in biochemistry from the University of Tübingen, Germany. He was also a research student at the Max Planck Institutes of Biochemistry and Neurobiology in Munich, Germany. In 2002, he received a PhD in Biology ‘summa cum laude’ from the University of Heidelberg, Germany. After receiving his PhD, Dr. Jasper moved to the University of Rochester Medical Center, first as a researcher in the department of biomedical genetics, then as a tenured research professor at the department of biology. He has been at the Buck Institute since the summer of 2012.

Dr. Jasper’s lab is interested in regulatory mechanisms that control stress tolerance, metabolism and aging. Current projects ongoing in his lab focus on the control of tissue regeneration, metabolic homeostasis, and cell death by insulin and stress signaling pathways. Most of these studies are being conducted inDrosophila melanogaster (fruit fly), taking advantage of the wide range of genetic, molecular, and genomic techniques available for this model organism. During his research seminar at the Buck Institute, Dr. Jasper summarized his lab’s projects, which fall under three main topics.

  • The interaction between the stress signaling pathway and insulin signaling, and its control on metabolic homeostasis and lifespan.
  • The development of the fly retina as a model system in which to assess the regulation of cell survival and cell death decisions. Also using this model to identify molecular and cellular mechanisms governing tissue recovery after genotoxic stress.
  • The study of stem cells in the fruit fly midgut epithelium to address how stress and aging influence the ability of these stem cells to self-renew, and whether optimizing stem cell activity can influence the aging process.

SAGE sat down with Dr. Jasper to ask a few more questions…

What is the big picture of your current research and how does it relate to aging research?

HJ: There are two aspects. One is what I started with, which is the metabolic homeostasis question. We study how the stress system impacts insulin and the metabolism of the animal. It is of course a fundamental problem not just in aging but also in diabetic patients. You need to understand how obesity results in insulin resistance and a decline in metabolic function. It has been shown that the stress signals, particular the signal called JNK, is actually causing the insulin resistance and obesity. In the aging field, we know that there is an age related insulin resistance and a decline of metabolic function as well. By reducing insulin signaling activity in invertebrates, such as the worm and fly, you can extend lifespan. In the mouse model, it is more complex because there is tissue specificity. Suppressing insulin signaling can be bad because you could end up with diabetes. But insulin signaling can also be beneficial, for example, in adipose tissue. When you knock down insulin receptors in adipose tissue, you end up extending lifespan in mice. The second aspect is stem cell function. We are asking fundamentally how aging impacts the regenerative capacity. We know that the decline of regenerative capacity is actually an anti-cancer mechanism. So there is a balance between maintaining regeneration and preventing cancer, and this is what we are trying to figure out. We are trying to improve the regenerative capacity but prevent dysplasia and cancer.

What is the project that you are most excited about right now in your lab?

HJ: The reason that we have so many projects is because I tend to get excited about many different things. So it is hard for me to choose. At this particular point, I am quite excited about the calcium oscillation. Because we developed a new tool, which allows us to look at what is going on in live tissue. And it gives us insight directly into stem cell biology. We can look at the activity when the animal is alive. The level of detail we can go to is amazing. That is what I am excited about in that project. And other projects that I discussed are also exciting, such as understanding hemostasis more globally in order to understand how commensal bacteria impact the gut activity and lifespan. This is where I am right now. But who knows, maybe next week I will be interested in somethings else [laughs].

We know that there are a lot of interventions that can regulate aging in animal models. Do you really believe any? If you have to choose one intervention to apply on yourself, what would you choose?

HJ: I think the dietary restriction is the most likely way to impact lifespan. But it’s also probably the hardest thing to do [laughing while eating potato chips]. I wouldn’t want to do it for sure. You also have to look at those things from the perspective of the quality of life. You’re not going to have a lot of fun on dietary restriction. So to me, it’s not worth it. Instead, we should understand the mechanism of calorie restriction and find out an intervention based on that mechanism to extend the quality of life without any negative effects. I believe that is really the challenge. For other interventions, I do think improving our commensal microbiome is going to have an impact. We have no idea how that would work. But I think there is a promising opportunity there. Another thing that I believe in is to improve the ability of the system to respond to challenges that will have an impact on aging. I do believe that when we are young, our bodies can respond to challenges like stress, damage etc. very effectively. I think this is a critical thing that we need to address. And one of the most promising answers would be regeneration.

After you got your PhD from Germany you directly became a faculty without doing a postdoc. How did that happen?

HJ: Things can happen right [laughs]? I did my PhD at the University of Heidelberg in Germany. This university is really one of best places to do life science in Europe. I was involved in a lot of developmental biology, and that was the best place to do it. My advisor was recruited to the University of Rochester, where we continued to some of the work. People in the University of Rochester were really excited about what we were doing. After I finished my PhD, I was looking around for a postdoc, and they really wanted me to stay. They first gave me a Research Assistant Professorship and then gave me tenure track. But I am not sure I would recommend this career path. Because normally you are allowed to apply for grants and get funded, but in reality you would hardly ever get funded. It’s because you are not ready to be independent as a Research Assistant Professor. So that would be a challenge. It was ok for me because I had learned to write grants at that point, and I was very lucky to work with outstanding graduate students at the time to publish good papers. And doing a postdoc in a big lab is not a bad thing: you learn to network, and you get to know new people, techniques, and the environment. It would help you develop your own research.

How is conducting research in Germany different or similar to academic research in the US?

HJ: The reason I stayed in the US is because I think the academic environment in the US is more dynamic due to the funding environment. It’s so challenging to get funded. It’s always a challenging environment that rewards you for being creative, efficient and productive. I feel like in Europe it matters more who you know than what you do. Never-the-less, Germany right now is a good place for research because they have invested in science quite heavily over the past 20 years. And the funding environment is great compared to the US. They have done a good job trying to break open the heretical system that I talked about. Now it’s very easy to become independent early on and less related to your mentor. Germany actually adopted a lot of great practices from the US. So the environment there is very good right now. Sometimes their funding environment is very tempting.

Why did you choose to study the fly?

HJ: I started working on developmental biology when I was an undergraduate student. I was at the Max Planck Institute for Developmental Biology in Tübingen. The director there was Nüsslein-Volhard, who is a Nobel Prize winning scientist. She did a big fly screening in the mid-80s where they identified basically every single gene that is required for early development. And when you looked at that work, pretty much everything we know, such as growth factors and singling pathways, ultimately were discovered and characterized in the fly. And it was all done in the early 90s. When I was an undergraduate student, I was working close to that but I wasn’t working on flies. I was working on frogs (xenopus), which is another classic developmental model. The problem with frogs was that it is very difficult to study genetics in frogs, because they have a lot of redundancy in their genome; there were no tools available. I was doing transcriptome analyses in the frog at the very early stage. I identified a lot of genes that were very interesting, and then I got stuck. I couldn’t do a knock out and I couldn’t do an over-expression. And next door, people were working on flies and they had mutants and could rescue these mutants. The ability to manipulate the system in the fly is so much better. So I decided to go to a fly lab for my PhD research. Once you understand what you can do in the fly, it’s very hard to go back. We have started to do mouse work now. I have to say that it is interesting, but it takes forever.

How do you manage so many people in your lab?

HJ: The exciting thing about coming to the Buck was that I was able to get a lot of independent and self-motivated postdocs. They are all very excited about what they are doing, and they have their own ideas. So all I need to do now is try to help them, either by helping them to narrow the focus of their work, or by helping them write papers or apply for fellowships. At this point, it‘s not a hard job for me anymore, because they are the ones that are driving the projects, and I am just there to support them. I already have 8 postdocs and 3 graduate students, and I don’t think I will go much more than this. I would say that maybe 15 people are the maximum for me. I like to meet with everyone once a week for half an hour for a one-on-one meeting.

How do you help your postdocs get jobs in academia or industry?

HJ: I help them as much as I can. But sometimes, it’s hard to give good advice. I can share my connections and network, and I know when there are job postings. But to advise someone to be successful in the current environment is hard. A lot of things depend on luck right now. But I always share my experiences and try to explain what I think would be good steps for each postdoc.

What do you do for fun? I know you like bike riding. Anything else?

HJ: I don’t like biking at all! I am from the northern part of Germany where biking is the way to go to work. I always do that, and it’s a good work out. Biking to the Buck is very hard because of the hill. It is terrible! I do bike maybe twice a week. I play soccer for fun. We play soccer on Wednesday every week at the Buck. The other fun is pretty standard: I go to the wine country, and to the beach. That is another reason to come work here.

For more on Dr. Jasper’s research check out the Jasper Lab Website.

Jonathon Fulkerson
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About Jonathon Fulkerson

After 15+ years as an IT professional. Jonathon decided to return to school in hopes of one day troubleshooting the most universal problem effecting all. Death, pain, and suffering by aging. As an undergraduate he is currently performing research in Dr. Richard Bennetts lab at the University of Southern Indiana, as well as volunteering for various organizations including the Buck Institute for research on Aging.

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