Impact Stories

What is your area of research?

Quite simply, muscle. However, muscle is actually quite complex because it is connected to everything and interacts with many systems, organs and cells in the body. Most people think of muscle as structural and essential to how the body moves, but it is also an important tissue for metabolic function, which is the body’s process for converting food and nutrients into energy. For example, muscle plays an important role in metabolizing glucose and Type 2 diabetes can develop when muscle is unable to carry out this function. Through our research, we want to understand why muscle may or may not be able to do this and many other vital functions.

In our research, we study two aspects of muscle: how the substances muscle makes – proteins, DNA and RNA – contribute to its structural and metabolic function and how muscle changes over time. More specifically, we are interested in the maintenance of muscle and how it preserves its function. In the lab, we study how external factors, such as temperature, medicine, exercise and glucose affect muscle. We also study how different conditions like aging, level of activity or a disease process like muscular dystrophy – a disease characterized by progressive weakness and loss of muscle mass – affect muscle.

We know a person loses 7-10% of muscle mass in a week of inactivity; however, a week of activity does not result in regaining 7-10% of muscle mass. Much of our research on the effect of inactivity on muscle is done in space through funding from NASA. In the anti-gravity environment of space, muscle is used differently than on Earth, leading to rapid changes as a result of disuse. As part of our research, we sent worms on three spaceflights to study the rapid changes associated with muscle disuse. Worms have a short lifespan so studies can be conducted more quickly than in other animals or humans and their small size makes them easy to transport and ideal for space experiments. What we observe in these experiments allows us to better understand conditions affecting muscles on Earth.

What scientific discoveries have been made by the Szewczyk lab?

Research in the lab focuses on understanding the molecular mechanisms involved in regulating muscle. This means we look for and study cellular processes contributing to or damaging muscle health and how muscle contributes to overall health. Through our research, the lab has made several foundational discoveries scientists can use to develop new and innovative treatments for conditions and diseases affecting muscle health.
For example, our lab identified signals coming into the cell and controlling protein breakdown in muscle. These signals either support or disable the production of protein. Understanding these signals creates new opportunities for scientists to develop and test innovative treatments for diseases where muscle decline occurs.

Identifying drug targets in muscle cells is another pathway for developing new treatment tools. Drug targets are proteins or other molecules in the body that interact with drugs. Our lab created an index of drug targets in the cell responsible for regulating muscle maintenance. This information can be used to guide the development of new medications to support muscle health in patients and help us understand why some medications cause muscle problems as a side-effect.

Our lab has also developed a way to measure decreases in mitochondria production in muscle cells. The mitochondria are the energy-producing parts of the cell and its production slows with age. Measuring mitochondrion production can also be used to identify early signs of certain diseases, such as muscular dystrophy. This information could be used in the future to develop new diagnostic tests and treatments. For example, we have recently shown in an animal model that increased levels of calcium are an early sign of muscle problems both in muscular dystrophy and with age. We are now examining if and how this translates into people.

You explained your research often uses worm models. How does your work with worms, and in particular, worms on spaceflights, translate to patient care?

The experiments using worms in space are designed to study how the role of genes in muscle change during spaceflight. There are two common changes in muscle cells during spaceflight, one to the metabolic genes responsible for energy production, the other to the cytoskeletal genes, which create the structure of cells and are responsible for cell shape and movement. To evaluate changes in muscle, the maximal strength worms can produce in space is assessed. Strength is also a key measurement of muscle health in people so we can use strength as a way to compare changes in genes that affect strength in worms to those of humans. The muscle and gene changes we observed in worms during spaceflight will now be assessed in astronauts.

If we consider the effect of spaceflight, muscular dystrophy and aging as having similar features of muscle loss, then learning what happens to muscle in one condition allows us to compare what happens in others, eventually leading to new information to guide targeted treatments for disease.

How has the Osteopathic Heritage Foundation’s support helped you advance patient care?

The Foundation’s investment has allowed me to focus on an emerging area of research analyzing multiple genetic and molecular interactions in large-scale datasets. This type of research allows scientists to investigate multiple interactions of cause and effect simultaneously, instead of one at a time. It speeds up the ability to assess and test which conditions affect diseases and gain insights into future clinical applications.
An example of this is a hydrogen sulfide study we conducted related to patients with Duchenne muscular dystrophy (DMD). DMD is a rare degenerative disorder typically diagnosed in young boys, for which there is no cure. Our data analysis of animal models with DMD, compared to those without, demonstrated the DMD models display sulfide deficits, which can be corrected with a readily available over-the-counter supplement. We hypothesize sulfide levels might be a way to diagnose the severity of DMD in patients. To this end, we have designed a clinical study for patients with DMD and look forward to conducting the study to test our hypothesis.

The research endowment established by the Foundation provided the funding for these studies. This is important because federal funding for rare diseases like DMD is primarily focused on finding a cure, but patients are still suffering from this disease and finding better treatments is important for patient care and quality of life. The findings from these studies are being used to design clinical trials to see if this readily available, over-the-counter supplement will improve muscle health in patients with DMD.

How does conducting your research at a college of osteopathic medicine and the osteopathic profession’s focus on treating the whole person influence your work?

The Heritage College and osteopathic medicine’s holistic approach to education and patient care aligns with the way I approach my work. The study of muscle is holistic. It is about looking at muscle as part of a whole person and understanding how it is affected by changes occurring both within and outside the body. This is the heart of what I do, looking comprehensively and systemically at what factors contribute to the body staying in balance. This is a core tenet of osteopathic medicine – the idea of homeostasis or the optimal functioning of the body needed to stay healthy.

What is next for your research?

I am excited to continue the aging and muscle research and to advance the hydrogen sulfide DMD research to clinical trial. There are also many opportunities to continue to conduct spaceflight experiments to enhance our understanding of muscle loss in space and on Earth. A newer body of research we are partnering on with NASA will investigate the effects of spaceflight on the microbiome, the microbes living in the gut, which are increasingly understood to affect the immune system and overall health.