Faculty Highlight: Justin Wolter – Genetics of risk and resilience in neurodevelopment

A single genetics course completely changed Dr. Justin Wolter’s career path. As an undergraduate at Utah State University, Wolter happened to take a genetics class during his last semester pursuing a bachelor’s degree in Psychology. Now, 17 years later, he joins UW-Madison’s Laboratory of Genetics and the School of Medicine and Public Health as an Assistant Professor. Dr. Wolter is using cutting-edge genomic approaches to study how genetic diversity shapes brain development, and how changes in development affect risk and resilience to neurological disorders.

Dr. Justin Wolter

Wolter got his Ph.D. from Arizona State in Molecular and Cellular Biology in the lab of Marco Mangone, studying how the evolution of microRNAs affects gene regulation. The Mangone lab used C. elegans as a model organism, and from that experience Wolters gained a deep love of basic biology. He went on to do postdoctoral work at UNC-Chapel Hill in the labs of Mark Zylka and Jason Stein, where he studied neurodevelopmental disorders and human genetics.  While there, Wolter and colleagues utilized an exciting approach to study molecular phenotypes of cells collected from many different individuals, grown together in a pool.  This pooled phenotyping strategy coupled with genome sequencing enables what the team called “cellular GWAS”, enabling a genome-wide association study on the cellular phenotypes.

 

Dr. Wolter is also joining CGSI as an affiliate member. As we welcome him, we asked a few questions:

Where are you from originally? 

I grew up in Vermont, where I loved the mountains and greenery of rural life. I spent most of my time playing in the woods, turning over rocks, and going as fast as I could on skis.

What attracted you to UW-Madison?

I had been to a few conferences at UW over the years, and always loved the scientific environment. Plus, no other school has a Terrace! When I started narrowing my interests in evolution and neurodevelopment, I learned of some of the great labs at UW that have shaped those fields, and have had my eye on UW-Madison as a forever home since then.

What are you most excited about coming here? 

There is so much to look forward to!  But most importantly, the people.  The depth and breadth of research is spectacular, where collaboration, not competition, is the norm. And UW’s stellar reputation for recruiting and training fantastic students makes it a perfect place to build a team full of nice people who are scientific killers.

What projects do you have planned for your lab?

The initial projects in my lab will focus on two questions in the context of human and mouse neurodevelopment using cutting-edge genetic, sequencing, and genome editing approaches.

The first project is investigating how common genetic variation affects outcomes in autism spectrum disorder. There are hundreds of genes linked to autism, many emerging environmental risk factors, and a staggering diversity of autistic features in patients. But even within tightly defined autism subtypes there is huge variation in patient outcomes. Genetic background is likely the major driver of this diversity. However, most of the current genetic approaches are correlational, and so we know very little about the molecular mechanisms by which genetic background affects autism severity. To address this, we are using libraries of genetically diverse human cell lines which can be differentiated into nearly any cell type in the brain. We then model an autism-relevant genetic mutation or environmental risk factor in specific cell types, and use cutting edge genetics and sequencing approaches to determine mechanisms by which genetic variation affects autism-relevant traits. The goal of this work is to discover how genetic variation affects molecular and cellular traits in the brain, and identify genetic modifiers of autism outcomes.

Our second project is aimed at discovering genetic pathways that allow specific neurons to be resilient to neurodegeneration. In nearly all neurodegenerative diseases some neurons are especially susceptible to the neurodegenerative cascade, while others can persist largely unaffected. What distinguishes these two outcomes is largely unknown. Using a mouse model in which changes in brain development progress into neurodegeneration, we are exploring what neurodevelopmental processes underlie neurodegeneration. We have identified molecular signatures that precede cell death, that allows us to explore genetic pathways that make specific neurons susceptible. But this also points to pathways that neurons employ to survive, which can guide hypothesis-based therapeutic strategies.

What led you to get interested in this area? 

I have always been drawn to neuroscience; there is something satisfying about using your brain to think about your brain. And in my opinion these projects touch on two of the biggest unanswered questions in neuroscience. Projects that really excite me are those where my technical expertise allows me to explore big questions in a novel way. This often leads to some unexpected yet exciting experiments, which was the case for both these projects.

 

Dr. Wolter is currently setting up his lab in the Genetics-Biotechnology Center and is accepting rotation students from the Genetics, Neuroscience, or Cell and Regenerative Biology Graduate Programs for the Fall of 2023.