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To die will be an awfully big adventure: PhD Program alum Peter Pan studies neuron aging

By April 13, 2018July 10th, 2023No Comments

Pan as a PhD student in the Garriga lab.

Chun-Liang (Peter) Pan wants to understand the genetic program of neuronal aging and how neurons interact with other cell types to coordinate responses to stress. He studies these questions by taking advantage of the powerful genetic tools and relatively short life span of our favorite worm, C. elegans.

Pan is currently Associate Professor at the Institute of Molecular Medicine at National Taiwan University. He describes his time as a PhD student in Gian Garriga’s lab as “one of the most rewarding phases in my entire life.” In addition to his thesis work on nervous system development and neurite pathfinding, it was here that he took courses in genetics and got a solid foundation in the basic biosciences. He also described his appreciation for the multidisciplinary nature of the HWNI program, and resulting exposure to the cognitive, systems, and engineering aspects of neuroscience.

Following his PhD studies, Pan was a postdoctoral researcher in Steve McIntire’s lab at UCSF, where he began his investigation of the genetic mechanisms that control aging of neurons in C. elegans.

Read on to learn more about Pan’s interesting career path, from National Taiwan University medical school to military service to studying fundamental neuroscience in C. elegans.

Pan with his family.

Georgeann Sack: How did you become interested in neuroscience?

Peter Pan: I was a medical doctor by training. I graduated from medical school roughly twenty years ago. After finishing required military service in Taiwan I received clinical neurology training. After that I began to think about what to do for the future. It is kind of frustrating to practice clinical neurology, because many diseases do not have a cure. I was very interested in studying the mechanisms behind those diseases.

I had this luck to get a fellowship from the Taiwan government, that offered me money to study for a PhD in another country. I was dating someone who is now my wife, and she was at UCSF then. So I applied for a school near the Bay Area, and that is how I got into the Neuroscience Program at Berkeley.

GS: What was your military service like?

PP: For my military service in Taiwan I basically stayed with the air force base and did nothing but stand by. We have an aircraft training program and I was a medical officer then. So I just needed to stay there the whole day without doing anything. If something happened I would need to rush to rescue, but no one expected that to happen. So most of the time I would stay in a small room and have nothing to do.

I actually spent my whole military life reading a very thick volume of the principles of neuroscience textbook. That really gave me a more global knowledge about neuroscience.

Also, I think people in the military have a very different background than medical students. Medical students were kind of privileged. They barely know outside of their small medical bubble. But people in the army were very different. I had a chance to talk to those people and understand how outside people see medical sciences and biological sciences, and that made me realize it is very important to communicate medicine and science to the general public. Especially, you need to use language that they can understand.

Pan as a PhD student in the Garriga lab.

GS: You came into the Berkeley Neuroscience PhD Program with a clinical background, so how did you end up in the Garriga lab?

PP: This is a very interesting history. As a clinician I thought that if I were to choose a lab to join, I should choose a lab that uses mouse as a model, because that is the closest model available to human. So I tried my first two rotations, one in stem cell biology and the other used mouse to treat some genetic disease, and those rotations didn’t work out for me. It was tragic, because I didn’t get anything.

I wanted to do a very different third rotation so that I can determine where I should end up. I was very interested in how the wiring of the nervous system was made through genetic mechanisms. There were not a lot of labs then working on this topic. So I set up an appointment with Gian Garriga and he was so friendly. He has this charm of convincing students that he would be a great mentor, and he was. He was one of the greatest mentors I have seen.

Another thing was that I talked to a different professor. He asked me what I want to do. I said I want to apply what I learn in basic science to translational, clinical application. That pretty much got him mad. He said you only need to care for an important and interesting question in science, but not about how useful it will be in the future. And I think that was very useful advice for me.

Pan as a HWNI PhD student.

GS: What was your experience like as a Berkeley Neuroscience PhD student? You became a PhD student just a few years after the program began, in 2003.

PP: I often say to other people that graduate life at Berkeley is one of the most rewarding phases in my entire life. Although the first year was extremely stressful. I took courses in genetics and the course was great but it also required an extensive amount of reading, endless homework assignments, and midterms. So it was very stressful for the first year, but it was also very helpful because as a clinician I don’t have a very solid ground in basic biosciences, and that helped me tremendously.

One thing I noticed that makes Berkeley a little bit different from other top schools in the United States was that people at Berkeley are not only extremely smart, they are also friendly.

GS: Tell me more about thesis work at UC Berkeley.

My thesis work focused on how neurons get positioned in the right place, and how their processes were guided to the right target cells. These were important questions, because without this, you are not going to make the right connections within the brain and that is critical for function.

Mouse and fly brains have a lot of neurons and is very complicated, so we used a tiny worm that lives freely in the soil. It is called C. elegans. It has only about 300 neurons and the genetic tools are very powerful.

We used those tools to analyze a few mutant worms. We disrupted some genes, and saw if that affected how the neurons move to their destination, or how axon or synapse got connected. We want to figure out genetic programs that specify migration of neurons and connection of their axons during development.

Figure from “C. elegans AP-2 and Retromer Control Wnt Secretion by Regulating MIG-14/Wntless,” Dev Cell (2008).

Figure from “C. elegans AP-2 and Retromer Control Wnt Secretion by Regulating MIG-14/Wntless,” Dev Cell (2008). Click image to view article in full.

GS: Was there one discovery you made during your PhD that you were particularly surprised by?

PP: One very surprising finding is that, during my second project, we wanted to work out a gene and how that gene controlled neuronal migration. We initially thought, and everybody hypothesized, that this gene must function in the neurons because it controls how neurons uptake materials from the outer environment, so it has to function inside the neurons. But it turned out that gene did not function in the neuron. It functioned in a non-neuronal tissue. That tissue secretes a signal to attract the neurons to undergo migration. This function was very unexpected.

That 2008 paper in Developmental Cell has gotten the most citations out of all my publications because it tells people a lot about how attractive and repulsive signals were recycled and secreted and formed appropriate distribution in the environment for the neurons to navigate through.

GS: You are currently Associate Professor at National Taiwan University. What made NTU a good fit for you?

PP: National Taiwan University has all kinds of disciplines like engineering, physical sciences, liberal arts, and the medical school. I am always very interested not only in the medical sciences but also the physical sciences.

Another important thing is that there was already a very well established C. elegans lab at the NTU campus. The principal investigator of that lab, Yi-Chun Wu, had spent a year in the Garriga Lab for her sabbatical so we kind of knew each other. I felt more secure and that I would get some advice and support from her. The colleagues and students at NTU were very helpful.

GS: Tell me more about the research you do in your lab now.

PP: For my current research I am focused on two topics. One is aging of the nervous system. The second is how the nervous system deals with stress, and how the nervous system passes information about stress to other tissues and coordinates the response of all the tissues in the organism.

Pan lab pics.

GS: How will your research advance our understanding of how the brain works?

PP: To make direct inference to human disease or human biology is probably not so easy, but many genes that we work on in C. elegans have similar counterparts in the human genome so maybe some of them will perform similar functions in the human brain.

For example, two years ago we published a paper about how C. elegans receives temperature information, and the worm used that information to determine how long it is going to live. At warmer temperature, animals live a shorter time, at cooler temperature animals tend to live longer. This had been shown in mouse, but it is difficulty to study because mice live for more than two years and their body temperature remains consistent. If you are going to study mutant, long-lived mice, it could suck up the entire PhD life of the students. C. elegans live roughly three weeks. We can analyze a couple of genes in a reasonable time. We found that genes sensitive to temperature change are functionally connected to transcription factors that control gene expression, many of them have counterparts in the human genome. Those transcription factors modify global gene expression patterns to adjust C. elegans life span to environmental temperatures. As these genes have counterparts in vertebrates, we hope that someday someone working with primates or mouse can help us to make this connection.

Another thing I found very interesting is that C. elegans, like humans, can be trained to like or dislike something. But if you want to figure out what genes control humans to display that kind of experience-dependent behavior, it is not going to be an easy task. With C. elegans we can manipulate a bunch of genes and see how the odor affects behavior, making the worm be attracted or not attracted.

GS: And are you looking at behavior in your lab?

PP: We have recently begun to work on behavior, and are looking at how worms are attracted by some odors or how they avoid some stimulation. For this we are setting up a lot of new equipment and imaging facilities.

Pan with his students at National Taiwan University.

GS: Who are your scientific heroes?

PP: Gian Garriga is always one of my role models because he was so available to the students. Although he did science using very rigorous and strict criteria, he was actually a very generous person. He was always generous about sharing ideas and even data. I think Gian was remarkable in that aspect.

During my PhD and postdoctoral studies, Cori Bargmann was an icon for all the young students in science. I think she is one of the best advocates of science and how to promote science to the public.

GS: What is the structure in your lab like? Is it very similar to a lab in the US or are there differences in training or the hierarchy of the lab?

PP: It is completely different. In the US, for neuroscience, because it is a PhD level program we have only PhD students and postdocs. Taiwan was completely different because students don’t want to study PhD because the biotechnical industry in Taiwan is not very strong. People with PhD are afraid that they could not find good jobs, and that prevents students from entering the PhD Program. So we mainly rely on Master’s Program students who only spend two years on their degree. The turnover of people in my lab is always really fast. I feel that I am always training new people.

GS: What publication are you most proud of?

PP: One is the aging paper that I published in 2011 in PNAS. It was the first paper that described aging of the neurons in C. elegans. Before that paper, people believed that neurons in C. elegans do not age. Our paper revised that concept and provided evidence that morphologically, neurons in C. elegans do change over time and there were specific pathways that modulate the speed of neuronal aging in C. elegans.

When I was writing that paper, my postdoc mentor was about to leave science and shut down his lab, and I was about to transition from the US to Taiwan, and my wife was about to deliver a baby. So it was a time when everything was rapidly changing and I didn’t even have a desk to sit down and write the paper. That was very difficult on me, but we managed to get it published. So that was a very memorable publication.

Figure from “A C. elegans Thermosensory Circuit Regulates Longevity through crh-1/CREB-Dependent flp-6 Neuropeptide Signaling,” Dev Cell (2016). Click image to view article in full.

The other paper was the 2016 paper in Developmental Cell. This paper took one year and three months for us to get it accepted. It argued against a finding previously published in Nature. The reviewers proposed a lot of concerns and questions so the editor initially rejected our paper. I went back and forth with the editors a lot of times and tried to convince her to give us a second chance. The revision took over a year, but eventually we convinced the editor and the reviewers that the paper should be published.

GS: It sounds like you like a challenge.

PP: Now publication has become more like this. The journals expect large amounts of data. It is getting harder and harder to publish papers.

GS: Is there anything else you want to share?

PP: To tell you the truth, when I was in Helen Wills, sometimes I thought the size of the program was pretty small compared to programs at other universities. But in hindsight I thought that the smaller program enables you to develop closer relationships with the students and faculty in the program. Although I majored in molecular and developmental genetics, being in Helen Wills exposed me a lot to the cognitive, systems, and engineering aspects of neuroscience. That is extremely helpful but I didn’t really realize that when I was a graduate student.

Also, I had a very stupid idea because I was a medical student by training, I thought I would be better off in a program that was associated with a medical school. And Berkeley was not like that. In the end I found the experience at Berkeley really dragged me out of my comfort zone and showed me a completely different aspect of scientific experience. I would encourage people to join Berkeley because it offers you a completely different perspective about science.

It is not good to spend too much emphasis on applying scientific research to clinical medicine or industry to boost up the economy. I want to say that science is science, and scientists should stick to science for its own good.

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