Q&A with Samuel Mackenzie, M.D., Ph.D.

Samuel Mackenzie, M.D., Ph.D., joined the Del Monte Institute for Neuroscience in July 2021 as a senior instructor in Neurology and Neuroscience. He recently completed his child neurology residency at the University of Michigan and a neuromuscular fellowship at The Ohio State University and Nationwide Children’s Hospital. His research interests lie in the development of gene-targeted therapies for neuromuscular diseases.

Tell us about your research.

My research is directly related to my clinical work. I take care of patients with neuromuscular diseases like spinal muscular atrophy, myotonic dystrophy, Duchenne muscular dystrophy, and different limb-girdle muscular dystrophies. These are all conditions that typically involve some kind of gene misspelling or deletion, and as a result, a particular protein involved in nerve or muscle function is not working properly or missing outright. My goal is to develop treatments that would replace or fix those proteins.

Currently, I’m working closely with Charles Thornton, M.D., who has had a long, distinguished career studying myotonic dystrophy. Myotonic dystrophy is a little different mechanistically in that it’s a trinucleotide repeat disorder affecting splicing of several downstream targets, but we think it’s amenable to a lot of the same strategies of gene and RNA manipulation. We’re collaborating with another lab to make a novel mouse model of this disease that, in genetic terms, would be the closest thing to what we see in humans. I was recently awarded a K12 career development award from the NIH to characterize this model. I’m also working to see if we can reverse some of the disease manifestations in this mouse by treating it with a promising therapeutic compound.

How did you become interested in your field of study?

While working on my Masters at the University of Delaware I began to segue into medicine. I had been a middle-distance runner in college and was doing graduate work in exercise science, thinking I would go in more of a physiology route, but ended up working on a project with kids who had hemiplegic cerebral palsy. I enjoyed the dynamic of working with the patients and their families and also began to appreciate the complexity of human movement. I was fascinated by the whole process of how a thought in the brain manifests as a physical action and what can happen if something goes awry in that pathway.

Why is it important for you to do research along with your clinical work?

I don’t make a big distinction between my research and clinical work. I believe that research is the best way to make a big impact on the conditions that we treat, but it’s also so rewarding to help kids with neuromuscular diseases using the treatments we already have available. I was in residency when the first systemic gene therapy was approved by the FDA for spinal muscular atrophy. It was a huge lift to get that treatment developed, but all of that work has paid off. A whole population of kids that had been dying of pulmonary complications on ventilators is now able to live more or less normal lives, if we can diagnose and treat them early enough. It’s been so powerful to see how life changing that therapy was and is for families.

What brought you to the University of Rochester?

In one word, it was the support. It was clear from day one that everyone here, Charles included, was committed to helping me do what I love doing and grow as a successful clinician-scientist. Rochester has a strong clinical enterprise in neuromuscular medicine and neurology as a whole. On the basic science side, there is a lot of cutting-edge research happening. I’m really interested in tapping into both of worlds and forming collaborations across disciplines.

Do you have a favorite piece of advice?

It’s important to make sure your science has meaning and that you find joy in what you do. It is easy to get caught up in the race for more publications or getting your work in a highprestige journal, but knowing you’re answering an important question is always going to matter the most. That said, feel free to ask me again in 10 years when my Ro1 application misses the pay line.