ABSTRACT

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Lisa Leinhos is first author on ‘Hypoxia suppresses myofibroblast differentiation by changing RhoA activity’, published in JCS. Lisa is a PhD student in the lab of Prof. Dörthe Katschinski at the Institute of Cardiovascular Physiology, University Medical Center, Georg-August University, Göttingen, Germany, investigating oxygen sensing and cellular differentiation.

Lisa Leinhos

How would you explain the main findings of your paper in lay terms?

If our skin was a building and its walls were destroyed, it would need many construction workers in order to rebuild it. In our body, these construction workers are represented by specialised cells. An important cell for repair is the fibroblast. As soon as a crack in the building's wall appears, fibroblasts jump into their best work wear and convert to an expert of restoration: the myofibroblast. Myofibroblasts are the bricklayers on the construction site, and provide the necessary material to rebuild the wall of our building. Myofibroblasts are very strong and able to close the crack in the building's wall easily. After the work is done, the crack is sealed in a process called scar formation. However, for this to be possible, fibroblasts must recognise and respond to the messages sent from the construction site in order to become a specialist in repair. There are a number of different messages, including the level of oxygen cells are exposed to. We aimed to understand how the amount of oxygen would affect the conversion of fibroblasts to myofibroblasts. Our research revealed that under low oxygen levels, fewer fibroblasts convert to myofibroblasts. This observation may help us better understand diseases related to impaired or overactive myofibroblast work.

Were there any specific challenges associated with this project? If so, how did you overcome them?

One of the experiments that I had to carry out was a RhoGTPase activity assay. These can be quite challenging. As part of the International Research Training Group 1816 (IRTG 1816), I was given the opportunity to join Prof. Anne Ridley's laboratory at the Randall Centre of Cell and Molecular Biophysics, King's College London, UK. During my highly productive time with the Ridley group, I received training on Rho-GST pulldown assays. Establishing this method in the Katschinski laboratory helped my project to proceed enormously.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

We first identified ARHGAP29 to be hypoxia-inducible in a wide range of cell lines, but its functional role was unclear. Finally, revealing that ARHGAP29 is involved in the observed hypoxia-mediated suppression of the myofibroblast differentiation using primary fibroblasts was a striking moment. Connecting the multiple pieces of our research puzzle, and building up an overall picture was truly a moment that stuck with me.

…revealing that ARHGAP29 is involved in the observed hypoxia-mediated suppression of the myofibroblast differentiation … was a striking moment.

Why did you choose Journal of Cell Science for your paper?

In this study, we addressed fundamental research questions by combining different scientific fields, such as cell biology, molecular biology and hypoxia research. By publishing our findings in the highly reputable Journal of Cell Science, we have obtained a unique opportunity to reach a broad scientific community.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

Dr Anke Zieseniss and Prof. Dörthe Katschinski extended excellent scientific supervision throughout my PhD. Additionally, Dr Katharina Wystub-Lis, my former undergraduate supervisor currently working at the German Research Center for Environmental Health in Munich, provided ongoing guidance and encouragement that helped me develop the fundamental motivation for my scientific research.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

From a very early age, my scientific curiosity has always been prevalent. At the age of eight, I owned my very own microscope, which enabled me to use the nature I was surrounded by while growing up to observe wildlife, dig up long lost treasures and fossils, and always hope to make a breathtaking discovery in my back yard. I first got introduced to academic science through a school internship at the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. From there on, the spark of curiosity that I had as a child grew brighter when I realized how much beneficial impact research had on society.

Primary skin fibroblasts cultured in normoxia (20% O2, left) and hypoxia (1% O2, right) stained for F-actin (red) and the myofibroblast marker αSMA (green). Fewer cells expressed the myofibroblast marker αSMA co-localised with actin stress fibers when cultured in hypoxic conditions.

Primary skin fibroblasts cultured in normoxia (20% O2, left) and hypoxia (1% O2, right) stained for F-actin (red) and the myofibroblast marker αSMA (green). Fewer cells expressed the myofibroblast marker αSMA co-localised with actin stress fibers when cultured in hypoxic conditions.

Who are your role models in science? Why?

I look up to old pioneers of natural science, such as German naturalist and explorer Alexander von Humboldt. The curiosity that drove him to be a true visionary of his time is inspiring, encouraging and applicable to ongoing scientific questions we are trying to explore and solve currently. In addition, I deeply admire Sir David Attenborough. His passion and enthusiasm for nature is truly inspirational. I have always desired to be as excited, passionate and devoted to my research as Sir David is about even the smallest ‘extraordinary’ creature on this planet.

I have always desired to be as excited, passionate and devoted to my research as Sir David is about even the smallest ‘extraordinary’ creature on this planet.

What's next for you?

I am currently finishing my PhD in molecular medicine and I am planning to start an independent research career abroad, in which I want to combine my early interest in regenerative cardiovascular science with my expertise in hypoxia research.

Tell us something interesting about yourself that wouldn't be on your CV

I enjoy touring national history museums. No matter how many times I visit an exhibition, I am always fascinated by the little details incorporated into each part and how nature aesthetics inspire art and designs. I also tend to be rather creative with drawing and doing crafts, which has been very helpful in research. Furthermore, my interest in nature and wildlife has resulted in an accumulation of random facts pertaining to animals – some definitely worthy of starting a conversation!

Lisa Leinhos's contact details: Institute of Cardiovascular Physiology, University Medical Center, Georg-August University, Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.

E-mail: lisa.leinhos@med.uni-goettingen.de

Reference

Leinhos
,
L.
,
Peters
,
J.
,
Krull
,
S.
,
Helbig
,
L.
,
Vogler
,
M.
,
Levay
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M.
,
van Belle
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G. J.
,
Ridley
,
A. J.
,
Lutz
,
S.
,
Katschinski
,
D. M.
, et al. 
(
2018
).
Hypoxia suppresses myofibroblast differentiation by changing RhoA activity
.
J. Cell Sci.
132
,
jcs223230
.