UMKC Muscle Biology Research Group

50 percent of muscle mass will be lost by the age of 70.

Skeletal Muscle

Store-operated calcium entry in muscle health, aging and fatigue
During aging skeletal muscles become weaker and hundreds of millions of individuals become afflicted by a condition named sarcopenia. While some of the changes that take place in aged skeletal muscles are directly related to muscle atrophy, changes in contractile apparatus function cannot fully explain the decrease in the specific force during aging. Our recent studies revealed that muscle aging is associated with compromised store-operated calcium entry (SOCE, see figure below), the elemental process for refilling of the intracellular calcium stores in skeletal muscles and the majority of cells studied to date. As calcium (Ca) entry is chronically reduced in aged muscle fibers, Ca storage in the muscles decrease making less Ca available for each contraction-relaxation cycle, leading to reduced contractile force and fatigue. Thus, my lab was among the first to demonstrate that effective SOCE is essential for normal muscle contractility. Our research involves the use of genetically modified mouse models, molecular-genetic manipulations, muscle contractility studies, calcium imaging and a number of biochemical and biophysical approaches. We always combine in vitro with in vivo approaches to create a broader understanding of physiological phenomena. A number of our studies are now being expanded to humans' patients with different muscle diseases.

Excitation-contraction (E-C) coupling

E-C coupling, illustrated in the figure below, is a cellular signaling process by which a depolarization signal from a motor neuron results in the contraction of a skeletal muscle fiber. Contraction is induced by a global release of calcium from the sarcoplasmic reticulum (SR) into the cytoplasm through the ryanodine receptor calcium release channel. Using an extensive immuno-proteomic approach, our research group in collaboration with Drs. Jianjie Ma at Robert Wood Johnson Medical School and Hiroshi Takeshima at Kyoto University has identified and characterized the function of several novel genes of the molecular machinery that regulates E-C coupling in muscle under physiologic and pathophysiologic conditions. In addition, in collaboration with Drs C-K Qu and Thomas Nosek at Case Western Reserve University and Dr. Hector Valdivia, University of Wisconsin, we have discovered a novel muscle specific phosphatase (MIP/MTMR14) that is essential for normal muscle function. Recent studies have demonstrated that mutations in the MIP gene relate to centronuclear myophathies and Charcot-Marie Tooth Syndrome, two devastating muscle diseases. Our long-term goal is to translate what we learn in the lab to the clinical environment to improve the lives of animals and humans suffering from muscle diseases.

Laboratory Members

Leticia Brotto, MD, Research Associate & Lab Manager
Sandra Romero-Suarez, PhD, Postdoctoral Research Associate
Todd Hall, BSA, Research Associate
Cheng Lin Mo, MS, Graduate Student Research Assistant
Michael Loghry, EMT, Undergraduate Research Assistant
Kendra Baker, BA, Research Assistant

Contact us

Marco Brotto, B.S.N., M.S., Ph.D.
MUBIG Program Director
UMKC School of Nursing
Health Science Building
2464 Charlotte Street
Kansas City, MO 64108
Phone: 816-235-1959
Fax: 816-235-5515