Friday, April 15, 2011

Asthma, vitamin D, and the biology of muscle at Experimental Biology 2011

Physician-researchers from Children’s National and the Sheikh Zayed Institute chaired several sessions and presented in others, at the most recent Experimental Biology annual meeting, located this year in Washington, DC. Experimental Biology is an annual meeting of nearly 13,000 scientists and exhibitors from six sponsoring societies and 16 guest societies. Key research efforts at Children’s National were featured, including two session highlights:

Genetic and Molecular Influences on Skeletal Muscle Size and Strength
This featured session was sponsored by the Muscle Biology Branch of the American Physiological Society and chaired by Sheikh Zayed Institute researcher Monica J. Hubal, PhD. Dr. Hubal began the session with a brief overview of the primary factors driving skeletal muscle size and function, including developmental conditions, nutrition, and activity level. In addition to these environmental factors, genetic variations between people are known to contribute significantly to differences in musculature and strength. These variations also may indicate how an individual will respond to diet, exercise, and disease.

Dr. Hubal invited two experts to explore these genetic factors. Maria L. Urso, PhD, of the U.S. Army Research Institute of Environmental Medicine began with an outline of 13 identified genetic influencers of muscle size and strength, describing how each impacts muscle growth and development. All were studied using a traditional, targeted approach where known muscle protein encoding genes were explored for genetic variations. For example, 18 percent of people do not make a muscle structural protein called ACTN3. Those lacking the ACTN3 protein have slightly smaller muscles than those that make the protein and are less likely to become elite weightlifters. Dr. Hubal says that it is a combination of these individual factors that could create significant variation in muscle size or strength. Variation in one of these genes alone won’t have much visible impact, but several polymorphisms can multiply together (a genetic concept called epistasis) to produce profound differences.

In the second presentation, Joseph Devaney, PhD, of the Research Center for Genetic Medicine at Children’s National presented findings from a genome wide association study (GWAS). The study looked at 1 million different DNA variants across the whole genome in relation to muscle strength and size for 800 college-aged students who participated in a resistance training study (an NIH-funded study led by Eric Hoffman, PhD, center director of the Research Center for Genetic Medicine and a principal investigator in the Sheikh Zayed Institute). Adopting a non-biased approach to identify DNA variations associated with musculature allows researchers to delve deeper into the combinations of factors that cause differences, and better understand how these factors interact to determine the make up of muscle. Dr. Devaney reported that his group identified eight new gene targets that can affect baseline strength and muscle response to resistance training.

Combining targeted research with wider scope studies like GWAS creates a better general understanding of how and why different people have different size muscles and different levels of strength. According to Dr. Hubal, her work in the Sheikh Zayed Institute, along with Evan Nadler, MD, studying the genetics of obesity and weight loss will benefit from similar approaches. Additionally, as the technology continues to improve and bring sequencing costs down, scientists will be able to study and compare the entire genetic make up of one person to others in the population, which will help illuminate rare variations not addressed by targeted or GWAS approaches, and creating a complete picture of the genetics that drive healthy muscle.

Vitamin D: Relevance in Infection, Inflammation, and Asthma

The session, sponsored by the American Federation for Medical Research was chaired by Robert J. Freishtat, MD, from the Research Center for Genetic Medicine at Children's National. The benefits of vitamin D to bone health are well documented. Now, studies show that the level of vitamin D in the body impacts many other body functions, according to Carlos A. Camargo, Jr., MD, from Massachusetts General Hospital in Boston. Stephen Teach, MD, chief of Allergy and Immunology at Children’s and leader of the IMPACT DC asthma program , showed that for children in metropolitan Washington, DC, the risk factors for asthma and vitamin D deficiency are shared. Dr. Freishtat presented data on how steroid treatments in asthma work to reduce inflammation in the epithelium and open the airways. Sabah Iqbal, MD, a researcher and emergency medicine physician at Children’s, presented laboratory findings demonstrating that vitamin D has many positive impacts in the lungs. Particularly noteworthy, vitamin D enhances the effects of steroid treatments, aiding in the reduction of inflammation and preventing the body from building up a resistance to the steroids.

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