Developing New Technologies to Investigate and Heal the Brain

Raju Tomer, who joined Columbia in 2016, wants to better understand the brain by improving the technologies that allow us to see inside it.

Tomer’s lab has a wide-ranging approach to that goal. Several years ago, for example, Tomer and colleagues developed a set of imaging and chemical treatment methods that can turn tissue samples of the brain transparent, giving scientists the chance to study them more easily and in more detail.

And late this summer, his lab published a paper in Nature Biomedical Engineering on a new tool that they developed that can cheaply capture high-level images of brain tissue that were previously only possible to capture with ultra-expensive lab equipment. Tomer hopes to democratize microscopy, a technology that allows scientists to explore wide-ranging biological systems, such as developing embryos, bacteria, and brain tissue.

Tomer sat down to discuss his lab’s new microscopy technology and his work more broadly.

How would you describe the research you do in general? What are your goals?

Our research is heavily focused on developing new technologies that will allow us to better understand how the brain works and what goes wrong in neurological conditions, psychiatric disorders, or as a result of substance abuse or addiction.

We’re still a long way from understanding how the brain works, and how neurological diseases like Alzheimer’s and Parkinson’s, and disorders like addiction or Schizophrenia, manifest in brain structure and function over time. So most of our current focus really is on improving the tools needed to help us tackle those challenges.

What makes this new paper important?

The imaging tools that we use to examine the brain and other tissues—known as light sheet microscopy tools—are very expensive, complex, and not easy to use. They're generally available only in well-resourced specialized labs or advanced core facilities, and aren’t particularly accessible in resource-limited settings.

So in this work we try to address that challenge of accessibility by using everyday components like a laser pocket projector and a Nvidia nano board, which cost a few hundred dollars, to build something similar.

We found that by combining these with some optical and computational tricks we could actually develop a high-performance 3D imaging system that is orders of magnitude cheaper but still gives us comparable or better imaging capabilities and a much more compact device footprint. We demonstrate its applicability to many different types of samples relevant to neuroscience and life sciences research.

Our hope is that by making these advanced imaging capabilities more broadly accessible, many researchers will be able to do research of this kind, broadening what we know about the brain and other organs.

You recently wrote a paper where you used microscopy to look at the effects of ketamine on a mouse’s brain. What made that question interesting to you?

Ketamine has been used as a recreational drug for a long time, and recently it’s become very popular as a fast-acting clinical treatment for depression. Our goal was to find out how it changes the brain over time. We found several interesting things, looking at its effects on the whole mouse brain. We found that ketamine changes the whole dopamine network in the brain, and also that some parts of the brain were positively impacted while others were negatively impacted. Exposure to ketamine over time led to a loss of dopamine neurons in the midbrain regions involved in social behavior. On the other hand, ketamine increases dopamine connections to the part of the brain that handles executive functioning. It also affects the part of the brain that deals with the senses, which explains why it has a dissociative effect.

What drew you to this work?

For me, the drive comes from the curiosity-driven excitement of working on really tough problems. A deep curiosity about how our brain works, how it changes, and how we can fix it is what drew me into neuroscience.

During my Ph.D., I worked on brain gene expression mapping to explore the deep evolutionary origins of our brains. Then, during my postdoc, I dived into developing microscopy, tissue processing, and data analysis techniques to map the finest details of neurons at the whole-brain level.

Now, I’m still driven by that curiosity, and by questions like how to integrate cutting edge brain mapping tools with machine learning, and how to get these new tools to researchers worldwide, especially in places where resources are limited.

What’s your favorite thing to do when you aren’t working on these problems?

I enjoy biking, traveling, movies, and playing table tennis. My 15-mile eBike commute from New Jersey to Columbia is one of the highlights of my day—it’s such a pleasure to ride along the Hudson! Above all, I love spending time with my family, especially helping my two fast-growing kids, watching movies, and shuttling them to their various activities.