Star Scientist of the Month- Dr Kathryn Wolhuter

"My grandpa died of a heart attack when my mum was 13 years old and I witnessed the long-term impact it has had. I decided from early on that combating cardiovascular disease was something really important to me."

27 April 2022

The Institute’s Star Scientist of the Month, Dr Kathryn Wolhuter is part of a team attempting to shed light on potentially the most important vascular gene ever discovered. Dr Wolhuter hopes her work will lead to new treatments for coronary heart disease and spontaneous coronary artery dissection (SCAD).

Congratulations on being named Star Scientist of the Month. You’re clearly very passionate about your work, how did you get into science in the first place?

I have such a cheesy answer to this but it was my primary school science teacher who really made me love science when I was a kid. He was one of those crazy mad professors who got us to do all sorts of experiments including attempting to push a minibus up a hill to teach us about physics. That sparked a curiosity in me and showed me that science is really fun. My grandpa died of a heart attack when my mum was 13 years old and I witnessed the long-term impact it has on families. I decided from an early stage that combating cardiovascular disease was something that was really important to me, so I did my PhD with the British Heart Foundation.

I came to Australia in 2018 and I was lucky to find a position at the Victor Chang Cardiac Research Institute straight away and then started working in Professor Jason Kovacic’s Vascular Biology Laboratory at the start of 2021. We’re currently working on the PHACTR1 gene, which is potentially the most important gene in vascular disease ever discovered. This is research that could really impact a lot of different people because of the variety of diseases that PHACTR1 has been implicated in, including coronary heart disease, migraine, fibromuscular dysplasia and SCAD.

The Kovacic Lab is at the leading edge of unravelling the complex role PHACTR1 plays within the vasculature and Professor Kovacic’s enthusiasm for the project is definitely contagious.

Are you making much progress with PHACTR1?

I have been developing methods to study PHACTR1 which measures changes in multiple factors including gene expression, protein abundance and metabolite production. I have some exciting new data indicating that PHACTR1 can regulate cell metabolism, but we are only just scratching the surface. The relationship between PHACTR1 and cardiovascular disease is highly complex. However, because PHACTR1 plays such a pivotal role in multiple diseases, if we can unravel how it signals, we could potentially treat a variety of illnesses.

Several labs around the world have attempted to understand PHACTR1 signaling, but none have tried to understand this gene at a multiples levels using an integrated, untargeted ‘omics approach. This work would not be possible without the facilities within the Institute’s Innovation Centre. The Centre has not only facilitated our ability to do perform multi-omics, but the quality of the output has been pushed to another level, especially with the Ion Mobility 6560 mass spectrometer from Agilent. Our end goal is to develop a complete picture of this gene’s function, gain an understanding of changes in this gene cause disease and ultimately create drugs that target PHACTR1 to treat vascular disease.

What does a normal day look like in the Innovation Centre?

Normally, I grow a few million human vascular cells which either have normal PHACTR1 expression or have PHACTR1 level altered up or down. I then extract metabolites, proteins and RNA which I analyze concurrently using mass spectrometry and RNA sequencing. By putting my samples though this analysis pipeline I am firstly looking to see which metabolites are present, such as sugars and amino acids, and see if they change with altered PHACTR1 expression using metabolomics. Then using proteomics, I can study if there are changes in protein levels that explain the alterations in metabolism. And finally, I’ll try to find out if altered protein expression is due to PHACTR1 regulating gene expression using RNA sequencing. I then use the bioinformatics facilities within the Innovation Centre to integrate my data and understand PHACTR1 signaling on multiple levels.

Once we have all that information, we can then start testing drugs on the cells to modulate PHACTR1 signaling and hopefully find the best treatments with minimal side effects on patients with vascular disease. It’s translational research at its best!

What’s been one of your proudest career achievements to date?

I think that would be at the end of my PhD. I had my PhD work accepted in Molecular Cell and that was a big moment for me. I basically submitted my PhD and had my paper accepted within about two weeks of each other. That was really nice because you put in all this hard work over several years with your PhD, so it was amazing to see that it really does amount to something at the end of it all.

Do you have any advice for women who are considering pursuing a career in science? Have you faced many challenges along the way?

I think times are changing. I've had a lot of mentors who I feel really do support women in science and have never told me less than that. But there have been times when senior scientists have made off hand remarks that can be incredibly demoralising. Even though we’ve made great strides in equality in science, we still have a way to go and far too often people make silly comments. I’m sure this happens in all industries not just science. But we need to ignore that commentary and focus on our achievements. I’m lucky that others have been battling for women to succeed in this field for a long time and there are lots of amazing resources out there and organisations supporting women in STEM, like Franklin Women.

Unfortunately, I think in school, a lot of people think that science isn't for girls. But that’s not true at all. If you enjoy it, don't give it up as a subject just because someone says physics isn't for girls, or only the boys do that subject. That’s nonsense. If you work hard in science you can succeed and you are at the exact same table as the guys.

Good advice. What do you do when you're not working hard?

I live in Manly and it very much reminds me of my family home in Cornwall in the UK because it's this lovely seaside town.

It’s great to live on the beach and get the ferry into work every day.

On the weekends, I spend my time kayaking and paddle boarding but I’m rubbish at surfing! I’ve just got my Permanent Residency so I can finally start applying for some grants.