Congratulations to William J Griffiths for winning the Schroepfer Medal.
The Schroepfer Medal recognizes a scientist who has made significant and distinguished advances in the steroid field. The medal was established to honor the memory of George J. Schroepfer, Jr., a leader in the sterol and lipid field for more than 40 years. The award aims to foster Schroepfer's ideals of personal integrity, high scientific standards, perseverance and a strong spirit of survival, tempered by charm and wit.
This spotlight will help you get to know Dr. Griffiths, including an overview of his current research and how AOCS has helped develop his career.
Plan to attend Dr. Griffiths' award presentation on April 28, 2021, 10:45-11:45 a.m. CDT (Chicago USA; UTC-5). You can join the livestream on our website, on FaceBook Live, or on YouTube Live. The abstract for this presentation is at the end of this blog post.
Can you tell us about current research?
My group uses mass spectrometry to study cholesterol biosynthesis and metabolism. At the moment the group’s research is focused on three areas of research: (i) sterols and oxysterols in neurodegeneration, (ii) oxysterols in the immune system, and (iii) oxysterol imaging in the brain. All three areas are interrelated and rely on derivatization technology developed in the group.
What was your reaction when you learned you had won the award?
When I heard the good news that I was to receive the 2021 AOCS Schroepfer Medal I was absolutely delighted. It is a huge honor to be following in the footsteps of great sterol scientists.
How has AOCS helped develop your career?
The AOCS through George Schroepfer and previous recipient of the AOCS Schroepfer Medal have had a huge influence on my career. I was lucky to work with Jan Sjovall (recipient 2004) for almost 15 years and he introduced me to the field of bile acid analysis. While working with Jan in Stockholm, I met Cedric Shackleton (recipient 2010) when he visited from California, and together we have collaborated for many years looking at metabolism of cholesterol precursors, particularly those elevated in Smith-Lemli-Opitz syndrome. When in Stockholm I also met Author links open overlay panel Ingemar Björkhem (recipient 2006) whose inspirational work on oxysterols I followed very closely. As is the case with Jan and Cedric, I have been lucky to collaborate with Ingemar over the last twenty years in the study of oxysterols and their importance in biology. In 2007 I move to back to Swansea University, and one of the important reasons for returning to Swansea was that the Chair of Research in the Medical School at that time was Steve Kelly (recipient 2016). Of course, much of my work on oxysterols has been massively aided by the 193-page textbook review written by George Schroepfer and published in Physiological Reviews in 2000.
Award presentation abstract
Bile acid precursors: Intermediates in cholesterol removal or signalling molecules?
The bile acid “family” consists of mainly of C24 and C27 acids and C27 bile alcohols. The dominant pathway, at least in mammals, is the neutral pathway starting with 7α-hydroxylation of cholesterol by CYP7A1. However, there are numerous minor pathways which may have evolved as a route to biosynthesise bioactive intermediates, and it is these minor pathways that have been the main interest of the author over these last three decades. Mass spectrometry in combination with chromatography has greatly simplified the study of bile acids and their precursors over this time. Today, LC-MS instruments run with minimal operator input 24/7, something that the author could only dream of in the 1980’s, and provide reproducible chromatography, mass resolution in excess of 200,000 and mass accuracy of < 5 ppm, also delivering automated MS/MS and MSn, allowing identification of cholesterol metabolites at pg levels, and now even mass spectrometry imaging in tissue. Influenced by two previous recipients of Schroepfer Medal, Jan Sjövall and Ingemar Björkhem, the author has utilised LC-MS to study oxysterols, the primary cholesterol oxidation products, and their down-stream metabolism to bile acids. Following Sjövall-like methods of sample preparation and derivatisation the author and his collaborators have uncovered many unexpected cholesterol metabolites in body fluids and postulated pathways for their conversion to bile acids. Many of these intermediates have turned out to be biologically active, acting as ligands to e.g. nuclear receptors and G protein-coupled receptors. This leads to the question, have these minor bile acid biosynthesis pathways evolved to generate signalling molecules, with the ultimate formation of bile acids in the hepatocyte just providing an added bonus. In this paper, the author will expand on this hypothesis detailing methods for sterol identification, including new methods for sterol imaging in tissue, and discuss some of the unexpected pathways uncovered.