MUSCLE RESEARCH: AN EXPANDING INQUIRY
Summer 2019

 

“Skeletal muscle is an amazing system. It is the one tissue where we can study the aging process, the influence of chronic disease, and the impact of physical activity in humans. It’s incredibly powerful.” Charlotte Peterson, PhD, has dedicated her career to the pursuit of muscle research and its impact on the scientific and health care communities. Her influence in the laboratory, and outside of it, has contributed significantly to the thriving research enterprise at the UK College of Health Sciences.

As a professor of geriatrics at the University of Arkansas for Medical Sciences, Peterson was primarily a basic scientist studying muscle in animal models, but she was becoming more and more interested in translating her research into humans. Drawn to the UK College of Health Sciences, Peterson joined the faculty in 2006 starting her tenure as the Joseph Hamburg Endowed Professor and the Associate Dean for Research. The College was rich in expertise in athletic training, physical therapy, rehabilitation, and other human health sciences and provided the perfect stage for her translational work.

At the time, UK had a robust muscle research program, but the College of Health Sciences was just beginning its own under Peterson’s leadership.

In 2009 Peterson and her colleague, John McCarthy, PhD, associate professor of physiology, received National Institutes of Health (NIH) funding to answer their originating question, “What are muscle stem cells doing in normal muscle?” Characteristic of good science, one question led to another question. One study led to the next.

The following year, the pair received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) to expand their study of stem cells in adult skeletal muscle adaptation. The findings were published in Development in 2011 with follow-up articles in The FASEB Journal and Cell Stem Cell, all high-impact journals, and challenged long-held dogma in the field.

“We were also interested in studying muscle loss within the context of different chronic diseases—whether it’s cancer or arthritis or heart disease. With my background in muscle and my interest in aging, sarcopenia (age- associated loss in muscle mass and strength) was a good place to start,” Peterson said. She and McCarthy have studied the effects of exercise on muscle stem cell dynamics during aging with funding from the National Institute on Aging (NIA).

They hypothesized that the loss of muscle stem cells that occurs during aging contributed to sarcopenia potentially laying the groundwork for stem cell therapy. “But what we’re finding,” she said, “is that muscle stem cells are not necessarily the solution.”

Once again at odds with commonly held scientific beliefs, Peterson said, “People didn’t want to hear that adding more stem cells wasn’t the answer.” This provocative work was published in Nature Medicine in 2015. “I would say people are still not happy about it,” she said. Peterson isn’t easily discouraged though, saying with a rueful smile, “It’s kind of surprising in some ways that we’ve managed to stay on top of the game, maintaining funding, when so many of our results have been negative. But you have to go where the data take you.”

Peterson has, indeed, stayed on top of the game. She has been continuously funded from the NIH for more than 25 years, and currently holds as a principal investigator a grant portfolio valued at more than $9.5 million, including grants from NIAMS, NIA, and more recently from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to investigate the mechanism through which resistance exercise causes skeletal muscle to communicate with adipose tissue to promote the burning of fat.

Translating Muscle Research to Humans

As she had hoped when she came to the College of Health Sciences, Peterson extended her research into human populations. Since 2014, she and Philip Kern, MD, associate provost for clinical and translational sciences at the University of Kentucky, in collaboration with Marcas Bamman, PhD, director of the Center for Exercise Medicine at the University of Alabama at Birmingham are studying the effects of the widely prescribed anti-diabetes medicine, metformin, on muscle growth with exercise.

Peterson’s human studies expand well beyond UK. She formed a productive collaboration with Mary McDermott, MD, professor of medicine at Northwestern University in Chicago, to study peripheral artery disease (PAD). In people with PAD, atherosclerosis in the femoral artery blocks blood flow so their leg muscles become ischemic (oxygen deprived) when they walk. When they sit and rest, blood is restored to the legs. “This constant ischemia-reperfusion causes muscle damage,” Peterson said, “There are some permanent changes in the muscle that we need to understand.”

For the last two years, Peterson and McCarthy have collaborated with Melissa McDiarmid, MD, MPH, at the University of Maryland School of Medicine, on a multi-project, multi-million dollar Congressionally Directed Medical Research Program Award, jointly funded by the U.S. Department of Defense and the U.S. Department of Veteran Affairs.

McDiarmid and her team have been studying veterans from World War II, Vietnam, and more recently from Afghanistan and Iraq who returned from battle with blast injuries and shrapnel embedded in their bodies— mostly in their muscles. Peterson said of her particular project, “It’s a biomarker study in rats to identify toxic metals and the long-term effects of embedded metals on health. I think it’s going to be really interesting and the results will provide critical data to better care for wounded soldiers.”

Peterson’s scientific productivity and excellence was recently recognized by The Glenn Foundation for Medical Research. She was one of 12 scientists to receive The Glenn Award for Research in Biological Mechanisms of Aging. The Glenn Award is a one-time $60,000 infusion of funds to augment research in the biology of aging. In this era of extreme competition and limited funding, unsolicited funds are nearly unheard of but richly deserved in Peterson’s lab. She, of course, is maximizing the award and is studying the process of senescence, which is permanent withdrawal from the cell cycle, and how it impairs muscle function and shortens lifespan.

She and McCarthy are also planning the submission of the competitive renewal of the grant that they have held since 2010. “Our data are taking us into the field of cell-to-cell communication – muscle stem cells communicating with a variety of other cells, and those cells influencing stem cell function. We want to know how these cells communicate with each other and why that is important for the ability of muscles to adapt. We are identifying entirely new roles for muscle stem cells and other cell types within muscle tissue and have some really nice preliminary data,” she said.

Mentoring the Next Generation of Muscle Researchers

Peterson’s influence is felt far beyond the laboratory. Brian Noehren, PT, PhD, FACSM, associate professor of physical therapy and director of the human performance and biomotion laboratories, said, “I credit my success and my science to Dr. Peterson point blank. She has pushed me, mentored me, and provided critical feedback. She sought opportunities for me that I would never have had as a junior investigator. I’m learning now as I’m further in my career that mentorship takes a considerable amount of time and energy, and I’m deeply appreciative to her for her investment in me.”

Post-doctoral scholars are drawn to Peterson’s lab from across the nation. Kevin Murach is currently in his fourth year as a post-doctoral researcher under Peterson’s mentorship. Murach said, “Dr. Peterson’s laboratory is one of the few in the world where I can marry my interests of exercise, satellite cells, and muscle growth using a mechanistic platform.”

A proven and productive mentor, seven pre-doctoral and 20 post-doctoral scholars have completed their training in Peterson’s lab, with many transitioning into tenure-track faculty positions as independent investigators at research-intensive universities. Peterson said, “It’s trying to balance giving students freedom, listening to what they’re interested in, and enabling them to study questions that really excite them. If they are interested and excited, they are going to work harder and enjoy being here.”

The Growth of Muscle Research

Over time, and under Peterson’s watch, muscle research in the College has expanded to occupy approximately 5,000 square feet of laboratory space on the fourth floor of the C.T. Wethington Building, which includes the Center for Muscle Biology, and the Biomotion and Human Performance Laboratories in the adjacent Multidisciplinary Science Building. Muscle’s importance to functional independence has drawn faculty investigators from different disciplines within the College, including physical therapy, athletic training, communication sciences and nutrition.

Nearly thirteen years after Peterson began her work at UK, this team of investigators is continuing and expanding muscle research. Today, collectively, they hold a grant portfolio valued at more than $17 million. Just as muscle is pivotal to overall health, muscle research is integral to the mission of the College of Health Sciences. Peterson said, “What we’re learning is relevant and should be taken into account when designing rehabilitation strategies or exercise paradigms for people. Evidence is the key and the only way we’re going to get evidence is through research.”

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