UTA nursing professor receives $6.575 million to attack musculoskeletal diseases

A University of Texas at Arlington College of Nursing and Health Innovation professor will use a series of grants totaling approximately $6.575 million during the next five years to attack a variety of debilitating musculoskeletal diseases.

Marco Brotto--the George W. and Hazel M. Jay Professor in the college, and an internationally renowned scientist and an expert in bone, muscle physiology and sarcopenia--recently obtained renewal for two grants, and funding for three new grants from the National Institutes of Health. These awards will further his work in tackling sarcopenia and osteoporosis, and support his new work on diabetic skeletal muscle disease and amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease.

Sarcopenia, the progressive loss of skeletal muscle mass and muscle strength, is prevalent in the aging population and affects 30 to 45 percent of people over the age of 60. It contributes to debilitating injuries, loss of independence, reduced quality of life in the elderly and more than $40 billion in health care costs in the United States alone, according to Brotto. Musculoskeletal diseases affect more than one in two adults and run up health care expenses of about $1 trillion around the world annually, Brotto said.

"Our view of aging is changing as we live longer," said Brotto, who heads the college's Bone-Muscle Research Center.

"Who would want to live longer and be sick, full of chronic disorders? Aging affects the human musculoskeletal, or MSK, system, causing an array of problems from premature deaths to serious disabilities," Brotto said. "Our studies over the next five years aim to advance discovery of how aging leads to osteoporosis, sarcopenia, diabetes, etc. This knowledge will translate into new diagnostics and treatments for MSK disorders and aging decline in MSK function."

Paul Fadel, the college's associate dean for research, said the outcome of Brotto's work could lead to significant living improvements for the elderly and ultimately for all people.

"With 10,000 people turning 65 each day, it is incumbent to seek solutions that further advance health and the quality of life for this population," Fadel said. "These studies will help us take gigantic steps in achieving that. As you age, your risk for falls increases because you're losing strength and balance. And this increases your risk for fractures, which can be very debilitating. Dr. Brotto and his team are tackling these problems from a variety of important angles."

Elizabeth Merwin, dean of the College of Nursing and Health Innovation, said, "These grants are a boon for the college, for UTA and for health care. These studies are potentially transformative. The outcome of the work of Dr. Brotto and his team of fellow researchers could significantly enhance the quality of life of the elderly."

Following are snapshots of the five NIH grants:

Bone-Muscle Crosstalk: bone cells regulation of skeletal muscle function--This grant is part of a special NIH mechanism called Program Project Grant, or PPG, involving four principal Investigators, or PIs, at Indiana University, the University of Missouri-Kansas City and UTA. Brotto is the PI of Project 2 of this PPG. He will use this $1.89 million grant to determine how bone cells can influence and change the function of muscles by releasing hormone-like molecules. Brotto has discovered that this process is altered with aging.

Regulation of store-operated calcium entry during muscle aging:--Brotto will use this $1.97 million grant to examine the mechanisms that contribute to the loss of strength in muscle during aging and determine if regulating certain proteins can improve the function of aged skeletal muscles. He is collaborating with Professor Noah Weisleder at Ohio State University.

Loss of a protein in muscle dysfunction in aging--With this $1 million grant, Brotto and his team will work with Christopher Cardozo, a professor at the Icahn School of School of Medicine at Mount Sinai, to investigate the role of a protein called "numb" in muscle function and weakness with aging. He believes the knowledge is likely to increase understanding of the causes of muscle weakness. "It could lead to treatments to prevent and mitigate weakness and frailty in the elderly," Brotto said.

Protecting the diabetic skeletal muscle by Nampt activation--The major objective of this $965,000 grant is to develop Nampt, or protein gene activators, to protect skeletal muscles from diabetes. "Diabetes is a metabolic disease associated with skeletal muscle injury," Brotto said. "This research project will generate high-impact pharmacological data through the discovery of new agents and develop molecular insights into preventing muscle injury in diabetes." Brotto is collaborating with Srinivas Tipparaju, an associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida.

Alleviating the progression of Amyotrophic Lateral Sclerosis, or ALS--Research shows that muscles appear to be primary targets as the ALS gene mutates. This is the primary research topic of Jingsong Zhou, UTA professor of kinesiology and associate director of the Bone-Muscle Research Center. In collaboration with the Zhou team, Brotto and his team plan to use this $750,000 grant to develop alternative therapeutic strategies for combatting ALS.

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