Conversations with Lipid Leaders: Dr. Miriam Greenberg

Posted on May 19, 2021

Greenberg Wayne State

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

I am a professor in the Department of Biological Sciences at Wayne State University, Detroit, Michigan. I am very grateful to WSU for providing an environment that allowed my research to thrive. I have been blessed with wonderful graduate students who came to our department from all over the world. The best ideas in my lab have come from the students.

I live in Ann Arbor with my partner. My young adult daughter lives nearby and is studying to be a teacher. She has a terrific way with young children. I think she will be a great teacher.

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

The exciting field of oxidative lipidomics continues to uncover new roles of lipid peroxidation in cellular and mitochondrial function, cell death pathways, and disease.

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 think that I always saw myself as a scientist, but I remember the exact moment that I knew that I wanted to focus on genetics. It was during my college genetics class, when I realized that every living thing is connected by the same basic genetic code. Obviously, there are variations among organisms, but the basic principle is universal. I am still in awe of that concept.

My high school chemistry teacher (Ray Rasmussen) was a wonderful influence because of her strong support. At that time, women were not equally supported in science. (Sadly, we have not yet reached a point of equality to this day).

What caught your interest and motivated you to get involved in the

research of cardiolipin and its role in mitochondrial and cellular function?

As a graduate student in Susan Henry’s lab in Albert Einstein College of Medicine, I studied how inositol synthesis was regulated and how inositol was a major regulator of phospholipid synthesis in the yeast model. When I started my own lab (1986), I wanted to continue to focus on lipid biology and to address important unanswered questions in the field. At that time, little was known about how inositol synthesis is regulated in higher eukaryotes or about the function of cardiolipin and how its synthesis was regulated.

None of the genes for cardiolipin-biosynthetic enzymes had been identified at that time. Mitochondrial lipid biology had an added level of complexity. But the universality of this lipid suggested that it played an important role in cell function, so that’s what I decided to focus on. With considerable naivete, I would add, as I had no background in mitochondria or cardiolipin research, which ruled out ‘hitting the ground running.’ My lab carried out many studies of cardiolipin synthesis and function with the idea in mind that it was important but without knowing of a link to any human genetic disorder.

In 2000, I was extremely fortunate to be on sabbatical in the Netherlands (Utrecht University) when it was discovered in Amsterdam by the group of Peter Barth and Ronald Wanders (Academic Medical Center) that the genetic disorder known as Barth syndrome was caused by defective cardiolipin remodeling. This was a major breakthrough by the young scientist Peter Vreken in the Barth/Wanders group. (Very sadly, Peter Vreken died later that year). Peter Barth and Ronald Wanders invited me to Amsterdam to talk about this remarkable finding, and they were wonderfully collaborative and generous. This was a major turning point in my research, as much of the cardiolipin research in my lab is directed at understanding the mechanistic link between cardiolipin deficiency and Barth syndrome. It was also a wonderful collegial event in my career, as my friendship with Peter and Ronald continues to this day. They are really incredible scientists and human beings. Peter put a name to a life-threatening genetic disorder, which gave families hope. The amazing Barth Syndrome Foundation was started by families at that time. Ronald’s studies of fatty acid metabolism are the pre-eminent studies in the field.

Your research surrounding cardiolipins has brought key insights into Barth syndrome. What are some of the key findings that your group has made that have implications for understanding and treating this condition?

One of our key findings is that cardiolipin deficiency leads to decreased acetyl CoA synthesis and perturbation of the TCA cycle. The likely cause of this metabolic dysfunction is that cardiolipin is required for 1) optimal activity of pyruvate dehydrogenase, and 2) iron-sulfur biogenesis. Therefore, cardiolipin-deficient cells have decreased acetyl CoA as a result of decreased pyruvate dehydrogenase activity. Further, activities of TCA cycle enzymes that require iron-sulfur cofactors, aconitase and succinate dehydrogenase, are decreased in cardiolipin mutants. Together, these deficiencies lead to decreased function of the TCA cycle.

These findings suggest that future treatments for Barth syndrome may include supplementation of simple metabolites that are limiting because of decreased TCA cycle function, and possibly drugs that increase activity of pyruvate dehydrogenase. They also potentially identify physiological modifiers of the Barth syndrome phenotype.

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

I enjoy gardening, bread baking, going on long walks, playing the piano. I took up sourdough bread baking during the lockdown and am fascinated by the complex contributions of the microbes to making a good sourdough. The lockdown also gave me time to ‘smell the flowers’ and garden with more thought and enjoyment. I used to play chamber music and hope one day to get back to it.

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

Favorite courses in college – Genetics and Music Theory

Hardest – organic chemistry

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

I very much appreciate receiving monolysocardiolipin from Avanti. This is the hallmark lipid that accumulates in Barth syndrome. (Walt Shaw was kind enough to send me for free an amount that I needed to carry out important experiments at a time when I couldn’t afford to purchase the catalog amount. I greatly appreciate his support).

We would like to thank Dr. Miriam Greenberg for taking time to catch up with us!

Click HERE to learn even more about her exciting research!