Conversations with Lipid Leaders: Dr. Dan Raben

Posted on February 22, 2021

19Teacher Raben

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

I’m currently a Professor of Biological Chemistry at Johns Hopkins University School of Medicine. I’ve been involved in lipid research since the mid-1980s, and I’m one of the two co-founders (with Binks Wattenberg) of the ASBMB Lipid Research Division. I grew up in a lower middle-class family in St. Louis Missouri. I received my BS in Chemistry/Cell Biology from the University of Michigan and my PhD in Biochemistry from Washington University.

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

This is always a difficult question to answer. There are a lot of exciting discoveries from the lipid research world and selecting one of them wouldn’t be fair to the others. And I just can’t decide which one is the “largest breakthrough”. There has been increasing interest in the role of membrane contacts in lipid transfer and the development and metabolism of lipid droplets. Both involve some intriguing studies. I am also particularly enamored by the recent structures of some of the lipid metabolism enzymes. These structures are providing a lot of insights into how these enzymes work, especially in a physiological context.

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?

I’ve been interested in science as far back as I can remember. I think I was convinced becoming a scientist would be cool when I was in the 6th grade. My earliest memory is being fascinated by my big blue “Human Body” book. What intrigued me was not so much the anatomy but the mystery of how it all worked. That led me into becoming interested in understanding how a lot of things in nature worked and, as they say, the rest is history.

What caught your interest and motivated you to get involved in the chemistry and biochemistry of lipids and lipid enzymes?

As a graduate student, I on worked on a project trying to understand how membranes induced the growth arrest of certain cells when they reached a confluent density. As a postdoctoral fellow in Dennis Cunningham’s laboratory at the University of California at Irvine, I was trying to find the membrane protein that was cleaved by thrombin to stimulate to growth of some fibroblasts. We were mutagenizing cells and looking for those that didn’t grow in response to thrombin treatment. I thought using growth response as an assay was less than ideal as it took hours to observe the thrombin-induced growth response. I wanted to use a faster assay. It was during this time the “PI Cycle” rose to fame which fueled my interest. In this cycle, agonists induced the hydrolysis of a phosphoinositide that led to the generation of inositol trisphosphate and diacylglycerol. It was also suggested that since phosphoinositides are often enriched in arachidonic acid, hydrolysis of these diacylglycerols could account for the observed release of arachidonate in response to agonists. I knew thrombin stimulated the release of arachidonic acid in platelets and decided to see if that could be used as an assay in fibroblasts. It worked, and I started looking at membrane lipid metabolism involved in the alpha-thrombin stimulated growth of some fibroblasts. It first became clear that some of the diacylglycerols whose levels increased in response to thrombin treatment were coming from a source other than the phosphoinositides. When I became an Assistant Professor, we showed that the diacylglycerols were initially derived from the phosphoinositides followed by diacylglycerol increases derived from phosphatidylcholine. That led us into thinking about the involved enzymes and their regulation.

How did you identify diacylglycerol kinases and phospholipases as the families of lipid-metabolizing enzymes that you wanted to study most? What is the significance of understanding these enzymes and controlling their activity?

As the studies above progressed, there was increasing interest in the localization and regulation of enzymes involved in generating diacylglycerols as well as phosphatidic acid. That’s how we got interested in the diacylglycerol kinases and phospholipases D. These enzymes, as many lipid metabolizing enzymes, are fascinating as they work at a membrane interface and are referred to as interfacial enzymes. Their mechanisms of catalysis and regulation often have so special or unique characteristics that bear on their physiological roles.

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

My two passions in my life are my family and my job as a scientist. I’ve been very fortunate that my hobby is actually my job. I do enjoy wines and recently got into learning about them. But I think more about science than I do wines. I know I seem boring, but I often wonder about the hobbies of artist and musicians like Picasso or Beethoven or what they did when they “retired”. I’m not so sure it was much their profession. In fact, many artists, including musicians, I know retire only to continue being engaged in their art albeit in a different capacity. That’s how passions work.

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

I think my least favorite and hardest classes were art classes. That may explain my answer above. I enjoy music and art, particularly sculptures, but I lack any hint of talent in these pursuits.

Do you have a favorite Avanti product or category of products? Maybe a product that you’ve found most helpful in your research?

I really don’t have a favorite. I just know that when I need a lipid, I know what company to turn to. Avanti has been a trusted and reliable source of lipids and a great advocate and supporter of lipid research and lipid researchers.

To learn more about Dr. Dan Raben's research, click HERE