Faculty Spotlight: Microglial-based Cell Therapies with Mariko Bennett, MD, PhD

Mariko Bennett, MD, PhD

Editor's Note: Meet the diverse, dedicated, and distinctive faculty who are discovering and developing pediatric life-changing solutions at Children's Hospital of Philadelphia Research Institute, in our monthly Faculty Spotlight series. This year, we're learning about the ways our faculty unwind and relax after working hard to improve pediatric health and care. In this Q&A, we meet Mariko Bennett, MD, PhD, an attending physician in the Division of Neurology and Leukodystrophy Center of Excellence. Stay tuned for more from our Faculty Spotlight series throughout the year.

Why did you choose to focus on your research specialty?

My interest is in the role that microglia, which are the resident macrophages of the brain and spinal cord, play in health and disease. It grew partly from necessity, as when I started my doctorate, few researchers were interested in these cells despite them constantly surveying synapses and being the first responders in disease. It was an exciting time because we learned that microglia develop from early progenitors outside of the developing embryo and can self-renew – unlike the traditional model of macrophages. I was trying to figure out how bone marrow-derived macrophages function differently than resident cells in brain disease.

In addition, many neurological therapies target microglia. Based on the idea that these cells engraft the brain and become "microglia," one example is the use of bone marrow transplantation to treat pediatric genetic white matter diseases, or leukodystrophies. Although my previous work has shown the cells don't exactly become microglia, the bone marrow transplantation approach often has a narrow therapeutic window due to toxicity and efficacy. I wondered whether I could make this approach better, and at least in preclinical models, we can.

Can you tell us about a current research project that you are excited about?

I am inspired by my work as a leukodystrophy doctor caring for children with genetic interferonpathies. Our lab is fascinated by the microglial reaction to interferons – proteins made in response to viruses – and we pursue microglia-targeting therapies such as viruses to which microglia are exquisitely resistant. Our (and others') findings show that interferon-sensing microglia appear pre-symptomatically in many seemingly unrelated neurological diseases. Much of our lab focuses on understanding microglial interferon responses and uncovering methods to use their sensors to deploy therapies.

What are the long-term research questions you hope to answer?

We aim to figure out how microglia contribute – and can be therapeutically targeted – across many pediatric neurological diseases. We hope that pursuit informs our efforts to create and deploy microglia-based cell therapies with more precision and less toxicity.

What do you enjoy doing in your free time when you're not working on research?

In addition to exploring Pennsylvania, reading, and drinking an unnecessary amount of coffee, I may be found watching my 4-year-old "play soccer" (also known as chasing butterflies and squirrels while wearing cleats). My daughter and I also make up bedtime songs, and we have nearly 100 songs I often share with my patients. Here's one of our hit singles:

My momma asked me what I wanted to eat
I said, "I don't care, I just don't want any meat."
She said, "That's highly unlikely,
Because about food you are flighty...
How about some cheese and macaroni?"
I said, "I only want some rigatoni!"

Rigatoni rigatoni rigatonirigaTONI
I want rigatonirigatonirigatoni ONLY

So she gave it to me, with a side of broccoli.
She set it down, and I said, "HEY!
Where's my cheese and macaroni?!"

How do you balance your research work with your personal interests?

It's a constantly moving target, and tough with the many hats I wear. I'm lucky that I really love my research work, and it helps that my husband is also a physician-scientist. Most importantly, we have an outspoken child who demands we stop talking about work to chase butterflies. I try to be as intentional with my "fun" schedule as I am with my work schedule, and I love planning our next vacation.