Conversations with Lipid Award Winners: Dr. William Griffiths

Posted on April 19, 2021

Bill Griffiths

The Schroepfer Medal recognizes a scientist who has made significant and distinguished advances in the steroid or sterols field. The award originated from colleagues of George Schroepfer, and it is presented to a distinguished scientist every other year at the American Oil Chemists Society Meeting.

Dr. Griffiths received this award for his work using mass spectrometry to study cholesterol biosynthesis and metabolism in three focused areas: (i) sterols and oxysterols in neurodegeneration, (ii) oxysterols in the immune system, and (iii) oxysterol imaging in the brain.

Tell us a little bit about yourself (current role, background, family, etc.)

I hold the Chair in Mass Spectrometry in Swansea University in Wales, UK. I have been in Swansea since 2007 having previously been a postdoc at the University in 1980’s. My interest is in cholesterol biosynthesis and metabolism, and we use mass spectrometry so identify and quantify sterols, oxysterols and bile acids. I run the group with my colleague Professor Yuqin Wang; we first met when we worked at Karolinska Institutet in Stockholm the 1990’s. Before Stockholm I was a lecturer in Chemistry at the University of the West Indies, Kingston, Jamaica. I learnt so much about teaching while in Jamaica and Karolinska Institutet is a marvelous place to do research.

What do you consider the largest breakthrough in lipid research in recent years?

This is a difficult question, but what interests me at the moment is the concept of different pools of cholesterol in the plasma membrane. It seems that the smallest pool i.e. “accessible cholesterol”, is the most important. Accessible cholesterol appears to be the key to regulating cholesterol synthesis, intracellular esterification of cholesterol and expression of the LDL-receptor. What’s more oxysterols are important in defining the size of this pool and this may be an explanation why some oxysterols have anti-bacterial and anti-viral activities.

Did you always envision yourself becoming a scientist? If not, what did you want to be when you grew up? Who influenced you to become a scientist?

Yes, I have always been interested in biochemistry, although my training is in chemistry. When I was very young I wanted to be a footballer (soccer player) and I always dreamt of being a sportsman of some sort, but I never had sufficient talent. Both my parents were clinically trained so becoming a scientist was not a surprise.

What motivated you to research the structural characterization of sterol compounds?

This was due to a combination of factors. I like chemistry, structures and reaction mechanisms. As I was trained in mass spectrometry I found that could combine this with my interest in chemical structures and sterols are the perfect size of molecule that you can visualize being synthesized in cells and broken down in the mass spectrometer. I guess too that when I got interested in sterols they were really out of fashion so I was able to carve out a little niche for myself.

Your current research interests seem to be centered around oxysterols. What has interested you about this class of lipids? What are the implications of a better understanding of oxysterols in human metabolism?

Oxysterols are challenging molecules and that’s what makes them so attractive. There are so many potential isomers, they are always present against a massive background of cholesterol and they don’t have strong chromophores or ionize well. What’s more some are unstable making their handling tricky. It’s funny when I first entered oxysterol research in the late 1990’s many people had demonstrated oxysterol activity in vitro, but there were few if any studies which showed a biological activity in vivo, and the prevailing view was that they were simply transporters of cholesterol back to the liver or just intermediates in bile acid biosynthesis. However, the work from David Russell in Dallas and Ulf Diczfalusy in Stockholm showing that macrophages make high levels of 25-hydroxycholesterol when challenged has convinced the lipid community that these molecules are important. I think the most exciting areas of oxysterol research at present are the involvement of 25-hydroxycholesterol in immunity and in the production of 24S-hydroxycholesterol by neurons and its implication in neurodegenerative mechanisms. I like to think that one of our current projects “mass spectrometry imaging of oxysterols” is going to be really important to furthering our understanding of the role of oxysterols in brain.

What are your hobbies? What do you like to do outside of the lab?

My main hobby is running. I run very slowly, but I go for a jog every morning, we live by the coast so I can run along the sea wall and watch the sun come up. I used to play rugby, a game a bit like American football but without the padding. I was never much good but I enjoyed it and like to watch International matches, but I get incredibly nervous when my team is playing.

What was your favorite and least favorite course in school? What was the hardest course for you while you were in school?

My best subject in School was Chemistry, I was never interested in modern languages, so that would be my least favorite. I wish I had learnt more mathematics at School. In the UK in the 1970’s at 16 you could only choose three subjects to concentrate on, I chose chemistry, physics and biology, I wish I could have done mathematics as well, but not at the expense of one of the other three.

What does winning the American Oil Chemists’ Society’s Schroepfer Medal mean to you?

George Schroepfer wrote the “classic” 195-page review on Oxysterols published in 2000, to receive an award associated with George Schroepfer is a great honor for anyone working in the Oxysterol field. To follow in the footsteps my mentors Jan Sjövall, Cedric Shackleton and Ingemar Bjorkhem tells me that I must have done something of scientific value along the way.

Dr. Griffiths' award presentation is April 28, 2021, 10:45-11:45 a.m. CDT. You can join the livestream on the AOCS website, on AOCS Fan FaceBook Live, or on AOCS YouTube Live.

Avanti's own Director of Research Chemistry and former postdoc of Professor Schroepfer, Dr. Shengrong Li, will be moderating the Schroepfer Medal Award Lecture.

Again, we would like to congratulate Dr. William Griffiths on his incredible achievements and thank him for taking time to catch up with us!

Click HERE to learn even more about his exciting research!