Michael Wolfgang of Biological Chemistry and the Center for Metabolism and Obesity Research on how going to school for pig farming leads to a career as a biological chemist
How did you become interested in studying metabolism of the brain?
WOLFGANG: In a very indirect way. In high school I had worked on a farm that grew horseradish and raised pigs and based on my experience there, I wanted to have my own pig farm. I actually went to college to become a pig farmer.
At the University of Illinois Urbana-Champaign, I took a course in reproductive biology and followed that with some lab courses and fell in love with reproduction and development. At that point in my life, I decided to go to graduate school and study primate reproduction at the University of Wisconsin, instead of becoming a pig farmer. For my postdoc, I wanted to work with an organism that was easier to genetically manipulate, so I went to work with mice at Yale in Xin-Yuan Fu’s lab. We found that if we removed a certain protein, STAT3, specifically in the brain, the mice became extremely obese. That was when I became interested in metabolism. I did a second postdoc with Daniel Lane in Biological Chemistry here at Hopkins before I started my own lab.
So sometime in that period you developed an interest in neuroscience too?
WOLFGANG: Sort of. I’m into studying the brain because so much is unknown and what is known can be conflicting. We know very little about the metabolic landscape in neurons in the brain and the fact that the field is wide open appeals to me.
Why is so little known about metabolism in the brain?
WOLFGANG: One of the reasons we know so little about how different cells in the brain metabolize anything is that it’s incredibly heterogeneous. Even within the small region of the brain that we work with, there are many different subtypes of neurons, and neurons are the minority population. There are more glia—support cells that bring in nutrients and remove waste from the neurons-- than neurons themselves.
To counteract this problem, we are developing tools to analyze and manipulate metabolism in specific subtypes of cells. For example, we can target a neuron or glial cell and then turn on or off specific enzymes with synthetic chemicals. In this way we are trying to vary the metabolites within individual populations of cells in the brain and determine the effects, like how this changes feeding behavior in mice.
What else is your lab studying?
WOLFGANG: We’ve been investigating several unique enzymes in the brain. One enzyme is very similar to several others found in the rest of the body that we know a lot about, but this one form of the enzyme is only found in neurons. These enzymes control how fatty acids are used for energy in muscle, heart and liver. But neurons aren’t thought to use fatty acids as an energy source, they use the sugar glucose, so we are trying to figure out why neurons have this enzyme and what is it doing there.
Why is it important clinically to study brain metabolism?
WOLFGANG: For patients with epilepsy, adopting a ketogenic diet that is high in fat and protein and low in carbohydrates can reduce the incidence of seizures. In this case, nutrient intake directly affects the severity of the disease, but no one knows for sure why that is. We hope understanding brain metabolism will lead to better treatments for epilepsy.
Diabetes and obesity are diseases of metabolism. Most of the treatments developed for these diseases have focused on the body’s cells and have largely ignored the differing metabolism of neurons. But, it is the brain that converts signals of hunger and fullness to actions that effect how we eat or exercise. Further understanding how our brains process metabolites may lead to better treatments for metabolic diseases.
--Interviewed by Vanessa McMains
Michael Wolfgang on studying how the brain uses nutrients: