#WhyIScience Q&A: A veteran neuroanatomist uses two decades of experience to traverse the complex structures of the brain

Charles Vanderburg talks about the importance of classical neuroanatomy in developing novel genetic tools to study psychiatric disease.

Allison Dougherty, Broad Communications
Credit: Allison Dougherty, Broad Communications

In 2013, neuroanatomist Charles “Chuck” Vanderburg received an unusual request. A sought-after expert in analyzing brain tissue on a micro-scale, Vanderburg was asked to study a unique specimen — a meteorite. Vanderburg went to work, using his microdissection skillset to study the composition of one of the oldest objects on Earth. 

At the Broad Institute of MIT and Harvard, Vanderburg uses his two decades of experience in classical neuroanatomical techniques — basic anatomy, tissue processing, molecular staining, and microdissection — to relate new computational, genetic techniques of mapping the brain to the brain’s key structures. Vanderburg works in Evan Macosko’s lab at the Broad’s Stanley Center for Psychiatric Research, where he uses both innovative genomics and tried-and-true neuroanatomical techniques to uncover mechanisms of psychiatric disease. He is helping to create single-cell gene expression atlases of the mouse, non-human primate, and human brains.

After obtaining his B.S. and Ph.D. at University of Pittsburgh and the University of Medicine and Dentistry of New Jersey, respectively, Vanderburg completed his postdoctoral fellowship at Harvard Medical School. At Harvard, he became fascinated by the modern tools used to study the brain, and joined the Harvard NeuroDiscovery Center as the director of its Advanced Tissue Resource Center. He had a concurrent appointment as an assistant neurologist at Massachusetts General Hospital, holding both positions for 16 years before coming to the Broad in 2018. In and outside of the lab, Vanderburg loves to explore; he's an avid skier and mountaineer. 

We sat down with Vanderburg to talk about his work, his long career on the cutting edge of neuropathology, and his advice to young neuroscientists in this #WhyIScience Q&A. 


Vanderburg uses this workstation to prepare brain tissue for examination under a microscope Credit: Allison Dougherty

What do you do at the Broad?

My job here at the Broad is to take my classical experience in neuroanatomy — which isn't something that's currently taught to a lot of people other than perhaps neurologists, neuropathologists, and anatomy professors — and to apply it to the new understanding of the human brain. The new understanding of the brain is digital, it's single-cell, it's genetic, it's spatial-transcriptomic. I am surrounded by young people who are mathematical and computational experts and know how to run the modern day tools of science. They needed an old-timey brain guy. And I've trained with some of the most old-timey brain people that there are.


What makes you excited about the work you do?

In my other life, I'm a fan of exploration. I love to ski, mountaineer, and climb some of the highest summits. I've skied on literally every continent and have a very adventurous spirit. I love traveling with groups of folks and I feel the same exact way about my mountaineering friends as I do my colleagues in science. Every day or every week, someone new will come to my laboratory with a new mountain to climb or a new scientific approach to explore.


What have been some of the most rewarding parts of your career?

I haven’t just worked on brains. I've worked on everything from copepods, which are bioluminescent sea creatures that flip themselves through the water, to the oldest object on the planet Earth. Somebody brought me a sample containing the Allende meteorite’s carbonaceous chondrites and asked me if I could help him to microdissect them so that they could determine the magnetic field strength of the universe when these objects had formed four-and-a-half billion years ago. The most rewarding thing about it all is that after I’ve gained all of this experience, I can share it and give back to other people.


Why do you feel it’s important to apply classical neuroanatomical techniques to newer, cutting-edge research? 

To study the complexity of the brain, we have to use a multimodal approach. I think of the brain as a machine that we know next to nothing about, and we’re trying to figure out how that machine works. We’ve been able to uncover hundreds of new cell types from tiny anatomical structures within the mouse brainstem with the recent tools that have been developed, like single-nucleus sequencing and spatial transcriptomics. 

We then need to apply the old-timey tools to new technologies to find out where these new cells are in the brain and how they relate to each other. Now we’re trying to apply these new tools to the mouse brain, the non-human primate brain, and eventually the whole human brain. If we don’t know what the component parts are doing and how they relate to each other, we'll never figure out how it works and how to fix it if things go wrong.


What is a current project you’re working on?

Right now, the NIH BRAIN Initiative is about to sequence a human brain at the single-cell level. It will be like the first human genome, so we’re going to have to procure a neuro-typical specimen, whatever that means. There’s age, diversity, gender, and many other very individual human attributes to consider. But when that gets done, we need to know that the first piece of machinery that we take apart is of good quality.

I’m part of a pilot program now with the NIH NeuroBioBank to compare tissue samples from brain banks across the country. They each have their unique tissue collection methods and I’m helping to do a direct quality comparison to try and understand which methods produce the most consistent results. And of course, another really important part of the pilot program is that we’re not just going to do this the old-timey way, we’re going to do it the new-timey way and we’re going to see if the two arenas of neuropathology mesh.


What advice would you give to someone looking to get into your field?

For me, advice-giving is based on listening and finding out what situation a young person might be in. The only thing I can say generally to young people when it comes to neuroscience — or any field for that matter — is that you need to love it. Sometimes it's going to be really hard and you're going to have to just stay the course. Science is a tough job because you can go for years without a win, and it can get to be very trying and frustrating. My advice is if you don't throw in the towel, you will succeed in one way or another. You will.