Nick O. Davidson is the division chief of gastroenterology at Washington University in St. Louis, where he has presided for more than a decade, and he has had professorships there in the departments of medicine, pharmacology and molecular biology, and developmental biology. He joined the associate editor ranks of the Journal of Lipid Research last summer and has been providing his expertise in gastroenterology and lipid-related liver conditions such as hepatic steatosis to the journal, which has, in turn, expanded its scope in that currently hot area of lipid research.
Davidson is a unique addition to the JLR leadership in that he is one of only a few associate editors who not only run their own laboratories but also are practicing physicians. In this interview, Davidson tells us about his career path, spanning from the early days as a bright-eyed student keen on biology in Liverpool, England, to the early days of his research career at Rockefeller University working with Dr. E.H. “Pete” Ahrens Jr., a founder of JLR, to the gene expression and regulation research he and his team are hard at work on now in St. Louis.
You were born and grew up in Liverpool, England. What began your interest in science? Was there a defining moment in your childhood or young-adult life that made you decide on a career in science and medicine?
My father was a physician and encouraged my interest in science growing up. I had an inspirational biology teacher in high school, Frank Swallow, who helped develop an interest in developing experimental approaches to fundamental questions. A key moment was when the axolotl (a type of salamander) in the biology lab lost a limb and we got to observe its regeneration.
What about gastroenterology intrigued you, and how did you come about choosing it as your specialty in medical school?
Gastroenterology is so engaging because the specialty encompasses an array of organ systems and pathophysiology. I was fortunate in medical school to have wonderful teachers and mentors, including Roger Williams, one of the founding fathers of liver transplantation. Dr. Williams’ scientific investigation into the etiology and management of liver failure stimulated my interests in hepatic lipid metabolism.
You received your medical degree at Kings College Hospital Medical School in London before coming to America and taking a position in the laboratory of cholesterol metabolism at The Rockefeller University in New York, working with Ahrens. Later, you completed your gastroenterology fellowship at Columbia-Presbyterian Medical Center. What helped you make the decision to leave England and continue your career in the U.S.?
I was extremely fortunate to find my way to Pete Ahrens’ lab at Rockefeller. Dr. Ahrens was on sabbatical in Cambridge, and I wrote to him regarding my interests in understanding hepatic lipid metabolism. Dr. Ahrens wrote the original description of primary biliary cirrhosis, detailing the hepatic and serum lipid abnormalities accompanying cholestasis. We met, and he invited me to join his lab as a clinical scholar. I spent three years primarily engaged in clinical investigation of cholesterol absorption and bile acid metabolism using isotopic and balance methodology.
How would you describe the research focus of your lab?
We focus on two areas of biology. The first area is post-transcriptional regulation of gene expression, specifically RNA editing. We are very interested in the biology of mammalian C-to-U RNA editing and the targets of the enzymatic machinery that mediate cytidine deamination of the apolipoprotein B (apoB) transcript. The field of RNA editing is undergoing a renaissance with the introduction of massively parallel RNA sequencing technology, and we are excited to have new tools to explore this biology in more depth. We hope to identify new targets for C-to-U RNA editing and to understand the role of Apobec-1 and its partners in intestinal biology, including inflammation and cancer.
The second area concerns the regulation of intestinal and hepatic lipoprotein assembly and secretion, specifically the genetic restriction points in chylomicron and very low density lipoprotein production. We are interested in the metabolic compartmentalization of fatty acids and neutral lipid substrates and their trafficking into storage or secretion competent particles. Within the liver, a major focus is toward understanding the mechanisms for compartmentalization of cholesterol for trafficking to the basolateral versus canalicular membrane and the factors that influence the development of gallstone formation.
For 12 years you were part of the faculty at the University of Chicago Medical Center. What do you feel were your most important contributions to science during your time there?
Our most significant contribution was the expression cloning of Apobec-1, the catalytic subunit of the apoB mRNA editing enzyme. We used Xenopus oocytes to express cDNAs from rat enterocytes to identify Apobec-1, the enzyme responsible for C-to-U RNA editing of apoB and the production of apoB48. We subsequently generated a knockout to verify its requisite role in vivo.