Keisuke Ishihara is a postdoc in the lab of Elly Tanaka and has been at the IMP for two years. He has been investigating how animal organs develop and form their complex structures, using organoids as models. After six years as a postdoctoral researcher, he has decided to make the next step in his academic career: in December 2022, he will take up a position as Assistant Professor in Computational and Systems Biology at the University of Pittsburgh School of Medicine. He will be hiring lab members starting early 2023.
How did your academic journey begin?
I grew up in Japan and the US. When I was in high school in Tokyo, I was part of the chemistry club – I was kind of a nerd. I liked mixing things and seeing them change colour or texture before my eyes. That started my journey: I went on to study chemical engineering for my undergraduate studies at Princeton University.
How did you go from chemical engineering to molecular biology?
For my thesis work, I had the chance to work in a lab that studied, surprisingly enough, fruit flies. When I first saw the beauty of the fly embryo under a fluorescence microscope, I was immediately drawn to molecular biology. I’m a very visual person, so, for me, microscopy was what finally connected chemistry to the dynamic shape changes of cells and tissues. At the same time, the engineering curriculum had trained me in physical modelling. So, combining all these approaches – microscopy, measurements, and theory – to address questions in biology motivated me to do a PhD. For my PhD in Systems Biology at Harvard University, I investigated how the frog egg – a giant cell – manages to find its own centre when dividing after fertilisation. I took a reconstitution approach by rebuilding the chemical reactions that happen inside the egg under the cover slip and by applying microscopy to understand how the egg organises in space and time. For my postdoc that spanned Dresden and Vienna, I continued with the reconstitution approach, but at the multi-cellular scale, using organoids as models to understand how stem cells can self-organise to build complex tissues and organs.
You will soon be heading your own research group. Can you tell us more about that?
When I started applying for group leader positions, I was looking for a nurturing environment for my research. I looked specifically for places with a strong focus in bioengineering and quantitative biology. I found a perfect fit at the Department of Computational and Systems Biology at the University of Pittsburgh. The faculty works on all sorts of biological questions like protein structure, cell signalling, genomics, development, and evolution with a strong underlying focus on quantitative approaches.
My goal as an Assistant Professor will be to lead a group that develops new chemical and genetic tools to sculpt 3-dimensional tissues to make better organoids. So far, the organoid field has largely focused on controlling cell fate. What I’m interested in is controlling the shape of organoids. How can we engineer organ size and curvature? In larger organs, there’s a lot of internal architecture that is hard to analyse and engineer, and my postdoc research was the first to address this challenge directly. My dream is to tune the shape of organoids and their internal structures along with cell fate to make designer organoids matched to specific applications. In my lab, I will start by focusing on cardiac and brain organoids, which I learned a lot about from groups here at the Vienna BioCenter.
What do you think is important to keep in mind as a mentor?
One important aspect is to keep conveying the excitement and motivation for research to the group. As a group leader, you don’t get to do much research yourself. One advice that I already received was to be a very good ‘cheerleader’ for your students. I’d like to achieve this by designing research projects with the students, in a way that aligns with their interests. I want my lab members to take ownership of their project and to feel like they are really bringing an important piece to the overarching puzzle. This will prepare them for anything they want to do in the future!
What’s an important take-away you would like your students to learn?
From my experience, I know that research projects can go in a direction that wasn’t planned. It’s important to realise that this is normal – there are times when things don’t work the way they were supposed to, and you are surprised. As researchers, I think we have to be patient and open to new ways of looking at things. This requires a lot of courage, too. I know all too well how it feels to have to give up on your favourite hypothesis or to realise that what you were doing was simply wrong. Embracing your curiosity, taking breaks, and coming back to the problem refreshed are what helps go through the frustrating times.
What kind of lab culture would you like to foster?
My job is to create a small, cohesive group where members can easily learn from each other. Open communication is very important. I want to make sure students are comfortable asking questions from the very beginning. With my lab members, I’d like to assemble and continuously improve a lab manual for both technical and non-technical aspects of research life. This should be a fun process and useful for new members.
Do you see your lab members taking your research out of the lab?
Yes, absolutely. I’d like to encourage creative forms of artistic expression that might come out of our science. In Vienna, I had the chance to participate in a public exhibition organised by the Max Perutz Labs. Thanks to the researchers and resident artists in the lab of Jörg Menche, the visitors could interact with my 3D organoid data in Augmented Reality via their smart phones. This created a very different level of intimacy from what a computer screen can do. It made me realise that my lab’s focus on 3D data opens up new possibilities for artistic expression and science communication.
You will soon be hiring students. What kind of profiles are you looking for?
Since our research will be multidisciplinary, combining wet and dry lab work, I will be looking for people who aren’t afraid of trying new things. Some students may be stronger in one or the other field, but ideally they would be curious to learn something about both. The focus of a student may even change in the course of their project. At Pittsburgh, I will be taking students from several PhD programs. If anyone is interested in joining my group, I’d be happy to advise on which program might work best for their background and research interests. The students I will be recruiting for fall 2023 should apply for a PhD program with December 2022 deadlines.
Published in November 2022.
Interested in Keisuke’s research? Email him at ishihara[at]pitt.edu.