DGP student investigates sexual dysmorphism in mice

Isabella Salamone is an eighth-year student in the Driskill Graduate Program in Life Sciences (DGP) who is studying sexual dysmorphism in mice in the laboratory of Elizabeth McNally, MD, PhD, the Elizabeth J. Ward Professor of Genetic Medicine and director of the Center for Genetic Medicine.

Salamone's research was recently published in the Journal of Clinical Investigation (JCI) where she and her team led by McNally discovered that glucocorticoid steroids improved muscle performance in mice through distinct, sex-specific molecular mechanisms.

Salamone will graduate from her program this spring and in the fall, will begin her postdoctoral fellowship at the University of Chicago where she will join the laboratory of Marcelo Nobrega, MD, PhD, to study gene regulation and asthma.

Read a Q&A with Salamone below.

Why did you choose Feinberg?

Of all the graduate programs that I interviewed with, I felt like the people at Northwestern understood the type of scientist that I wanted to become. I felt like everyone was really interested in practical questions, but they didn’t shy away from interesting dives into weird corners, so it felt like I could come here and do something that could have real relevance to human health.

What were your research interests coming into Feinberg and did they change?

When I was an undergrad, I did research in a strawberry sex chromosome lab. Coming into graduate school, I wasn't sure if I wanted to stay in ecology or if I wanted to move into more translational styles of medicine. So, I looked at lots of different graduate programs, and Feinberg's DGP program ended up being the place where I felt the most camaraderie and research interests.

I didn’t really have any research interests at the time I applied, but it turned out during my time at Northwestern that I’m still interested in the role of sex in describing different types of phenotypes and outcomes. I would say now that my two primary research interests are sexual dimorphism and gene regulation.

What was the motivation behind your JCI paper?

Dr. McNally is really interested in how dosing regimen plays a role in the body’s response to glucocorticoid steroids. She became interested in this through work done by a former post doc in her lab, which showed that if you decreased glucocorticoid dose from once a day to once a week, you saw benefits to the muscle.

The big finding Dr. McNally was concerned about was that if you take glucocorticoids chronically, you get muscle weakness, which is also known as atrophy, and is pretty well reported amongst patients who take glucocorticoids not just for muscular dystrophy, but also autoimmune disorders, lung disease and even COVID-19. Because of this, she was interested in expanding her investigation to this once weekly dosing regimen in uninjured muscle models since many people who receive chronic glucocorticoids don’t have an underlying muscle injury.

I started this investigation not really knowing where it was going to go. But after I treated the mice and we started investigating the mechanisms weekly, I found that the males and females were actually having these very distinct responses. They both had improvement in strength, or what we called muscle performance, but it seemed like the processes by which they got to that end point were different.

How could your findings help improve outcomes for patients who take glucocorticoids?

Specifically, we found a couple of distinct features in male versus female responses. For example, females had this really distinct lipid remodeling phenotype and the males did not. A well-known side effect of chronic glucocorticoids is weight gain, which comes from adipogenesis, and we saw mitigation of that phenotype in females, but we didn’t see it in males.

So, if there’s a particular side effect that you’re worried about mitigating, doing a reduced regimen may not produce the same effect in males and females. I hope that a direct effect of my findings would be that they influence how physicians and scientists think about the role sex plays on a certain outcome.

What advice would you give to prospective and current medical students?

Many institutions like to say that they’re interdisciplinary, and to a certain extent that probably is true, but I really feel that at Feinberg it is very true. If you don’t necessarily realize that coming in, you may take it for granted or not know how to take advantage of your access to a huge range of knowledge and fields. There’s no reason to be scared to pursue something that’s taking you off in a new direction because there’s always this network here that can support you. I've felt lucky, but I’ve realized it’s just a trait of Northwestern.

Source:
Journal reference:

Salamone, I.M., et al. (2022) Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms. Journal of Clinical Investigation. doi.org/10.1172/JCI149828.

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