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Department of Kinesiology
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Our laboratory focuses on two different areas of genetics: understanding the role of genetics (gene variation) in explaining how different individuals respond to various exercise programs and why similar people can respond differently to the same stimulus. And, we are examining how exercise/physical activity can influence DNA itself (e.g., telomere biology, epigenetics). Members: Stephen M. Roth, Ph.D., Professor and Lab Director Andrew Venezia, PhD student in the NACS program Former Postdocs and Ph.D. Students: Steven Prior, Ph.D., 2005 - currently Assistant Professor, Univ. Maryland School of Medicine, Baltimore Sean Walsh, Ph.D., 2006 - currently Associate Professor, Central Connecticut State Univ. Dongmei Liu, Ph.D., 2008 - currently Assistant Professor, University of Shanghai, China Ryan Sheppard, Ph.D., 2010 - currently research officer, U.S. Navy Andy Ludlow, Ph.D., 2012 - currently Postdoctoral Fellow, University of Texas Southwestern Medical Center Lisa Guth, Ph.D., 2014 - currently Postdoctoral Fellow, University of Michigan Sarah Witkowski, Ph.D. (Post-doctoral fellow) - currently Assistant Professor, Univ. Massachusetts Lab Projects: Dr. Roth has formal training in both exercise physiology and genetics. The work of the NIH-funded laboratory is focused on two areas: 1) Understanding the role of genetic variation (and environmental interaction) in determining inter-individual differences in skeletal muscle traits, exercise adaptations, and other health-related phenotypes. 2) Exploring the role of physical activity in altering DNA structure, including investigations of both telomere length and epigenetics (e.g., DNA methylation). Recent student-led projects include analysis of the role of acute and chronic exercise in telomere length and telomere biology in mice; molecular analysis of the impact of genetic variation in the androgen receptor gene on muscle gene regulation; investigation of the role of physical activity ancestry in body composition, metabolism, and gene expression in mice. The Functional Genomics Lab also collaborates with other groups on a variety of genetics-related projects, including studies of hypertension and exercise responses, and exercise as a moderator of genetic risk of dementia. Publications: Books: Roth, S.M. (2007). Genetics Primer for Exercise Science and Health. Champaign IL: Human Kinetics. ISBN: 0736063439. (see Human Kinetics website) Pescatello, L.S., S.M. Roth (Co-editors). (2011) Exercise Genomics (in the Molecular and Translational Medicine series). Humana Press. 287 pages. ISBN: 9781607613541. (see Humana website) Research Articles: Search PubMed for recent publications Recent, representative publications (* indicates student advisee): Sheppard, R.L.*, E.E. Spangenburg, E.R. Chin, S.M. Roth†. Androgen receptor polyglutamine repeat length affects receptor activity and C2C12 cell development. Physiological Genomics, 43: 1135-1143, 2011. Sood, S., E.D. Hanson, M.J. Delmonico, M.C. Kostek, B.D. Hand, S.M. Roth, B.F. Hurley†. Does insulin-like growth factor 1 genotype influence muscle power response to strength training in older men and women? European Journal of Applied Physiology, 11: 743-753, 2012. Ludlow, A.T.*, S. Witkowski, M.R. Marshall*, J. Wang*, L.C.J. Lima*, L.M. Guth*, E.E. Spangenburg, S.M. Roth†. Chronic exercise modifies age-related telomere dynamics in a tissue-specific fashion. Journal of Gerontology: Biological Sciences, 67(9): 911-926, 2012. Deeny, S.P., J. Winchester, K. Nichols, S.M. Roth, J.C. Wu, M. Dick, C.W. Cotman†. Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ɛ4 carriers. Alzheimer’s and Dementia, 8: 352-256, 2012. Ludlow, A.T.*, L.C.J. Lima*, J. Wang*, E.D. Hanson, L.M. Guth*, E.E. Spangenburg, S.M. Roth†. Exercise alters mRNA expression of telomere-repeat binding factor 1 in skeletal muscle via p38 MAPK. Journal of Applied Physiology, 113: 1737-1746, 2012. Guth, L.M.*, A.T. Ludlow*, S. Witkowski*, M.R. Marshall*, L.C.J. Lima*, A.C. Venezia*, T. Xiao, M.-L.T. Lee, E.E. Spangenburg, S.M. Roth†. Sex-specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring. Experimental Physiology, 98(10): 1469-1484, 2013. Ludlow, A.T.*, E.E. Spangenburg, E.R. Chin, W.-H. Cheng, S.M. Roth†. Telomeres shorten in response to oxidative stress in mouse skeletal muscle fibers. Journal of Gerontology: Biological Sciences, 69 (7): 821-830, 2014. Roth, S.M., T. Rankinen, J.M. Hagberg, R.J.F. Loos, L. Perusse, M.A. Sarzynski, B. Wolfarth, C. Bouchard†. Advances in exercise, fitness, and performance genomics in 2011. Medicine and Science in Sports and Exercise, 44 (5): 809-817, 2012. Roth, S.M. Critical overview of applications of genetic testing in sport talent identification. Recent Patents on DNA & Gene Sequences, 6: 247-255, 2012. Roth, S.M. Genetic aspects of skeletal muscle strength and mass with relevance to sarcopenia. BoneKEy Reports, 1, Article number 58: 1-7, 2012. Perusse, L., T. Rankinen, J.M. Hagberg, R.J.F. Loos, S.M. Roth, M.A. Sarzynski, B. Wolfarth, C. Bouchard†. Advances in exercise, fitness, and performance genomics in 2012. Medicine and Science in Sports and Exercise, 45(5): 824-831, 2013. Guth, L.M.*, S.M. Roth†. Genetic influence on athletic performance. Invited review for Current Opinion in Pediatrics, 25: 653-658, 2013. Ludlow, A.T.*, L.W. Ludlow, S.M. Roth†. Do telomeres adapt to physiological stress? Exploring the effect of exercise on telomere length and telomere-related proteins.” BioMed Research International, Article ID 601368: 1-15, 2013. Wolfarth, B., T. Rankinen, J.M. Hagberg, R.J.F. Loos, L. Perusse, S.M. Roth, M.A. Sarzynski, C. Bouchard†. Advances in exercise, fitness, and performance genomics in 2013. Medicine and Science in Sports and Exercise, 46(5): 851-859, 2014. Roth, S.M. Physical activity may improve aging through impacts on telomere biology. Kinesiology Review. 4: 99-106, 2015. Loos, R.J.F., J.M., Hagberg, L. Perusse, S.M. Roth, M.A. Sarzynski, B. Wolfarth, T. Rankinen, C. Bouchard†. Advances in exercise, fitness, and performance genomics in 2014. Medicine and Science in Sports and Exercise, 47(6): 1105-1112, 2015. Venezia AC, Guth LM, Spangenburg EE, Roth SM. Lifelong parental voluntary wheel running increases offspring hippocampal Pgc-1α mRNA expression but not mitochondrial content or Bdnf expression. NeuroReport, 26: 467-472, 2015. Lab Equipment The Functional Genomics Laboratory in the Department of Kinesiology at the University of Maryland is a ~1000 sq ft wet lab dedicated to functional genomics-based laboratory and computer analysis procedures, including DNA extraction, PCR, both Taqman and RFLP genotyping, electrophoresis, telomere length/telomerase, and in silico genetic analysis. The lab is equipped with large capacity cold storage space, including 4°C (~70 cu ft) and -20°C refrigerators and freezers, four MJ PTC-100 and one MJ PTC-200 (gradient) DNA Engine thermal cyclers, large and small gel electrophoresis stations, the Victor2 microplate reader (fluorescence polarization, absorbance, luminescence, etc.), the Applied Biosystems 7300 Real-Time PCR System (Taqman), UV transillumination and gel photo documentation center (Kodak EDAS system) with dedicated computer and imaging software, GeneQuant DNA/RNA spectrophotometer, Type 1 water system with DNase/Rnase-free capabilities, large and small refrigerated centrifuges, chemical hood, hot plate stirrers, water bath, ovens, heating blocks, measurement scale, pH meter, vortexes, microwave oven, dedicated ice machine, and several computers. The Department of Kinesiology maintains two -80°C freezers with backup support systems for storing tissue samples. The University of Maryland maintains a DNA sequencing core facility on campus, and a microarray core facility on a nearby campus, both of which are available to our lab for on-going projects. The laboratory also maintains close collaborations with the Molecular Systems Laboratory, directed by Dr. Spangenburg, in the Department of Kinesiology. Dr. Spangenburg's lab is well-equipped for cell culture and molecular biology techniques. Background Information: Why is the study of genetics important? To put it simply, genes make proteins that influence our body's structure and function. The insulin gene, for instance, results in the production of the insulin protein that is important for sugar metabolism. Researchers estimate currently that humans have about 23,000 genes. More importantly, we all have the SAME GENES! But we're all different, so how can that be? Although we all have the same genes, slight differences (called sequence variations) exist in a gene's structure and can affect how that gene functions in the body. In other words, the letters that make up the spelling of each gene can be slightly different in different people, which can then influence when a gene is turned on, how much protein it makes, or how well the produced protein functions. When you hear someone say, "the gene for this or that" they are actually referring to the gene's unique letter sequence. These sequence variations (known as SNPs or "snips" in the research community) are what make you unique (in part!) and different from everyone else (identical twins being an exception: same gene spelling!). But we mustn't forget one important factor: the ENVIRONMENT! In this case, environment means everything from child development, nutrition, drug use, disease and even EXERCISE (our favorite environmental stimulus). So genes and gene variations work within different environments to impact a person's physical structure and function. Certain gene and environment combinations can mean a predisposition for some individuals to certain diseases, not to mention differences in their ability to respond to various diet, exercise, or drug treatments. So why is the study of genetics important? Studying genetic variation in the context of different environments will help us learn why some individuals are predisposed to disease, why some individuals don't respond well to an exercise stimulus (or response very well!), why some folks can improve diabetes with diet and exercise while others require drug therapy, etc. In other words, both the environment (what you do and what is done to you) AND your genetic make-up affect how your body will function; we're out to study both, especially in the contexts of aging and exercise. How do we study the impact of genetics on health? Using equipment in our Functional Genomics Laboratory in the Department of Kinesiology, we can determine the specific sequence variation of a specific gene for our study volunteers. When we determine a "candidate" gene of interest that we think might influence how a person responds to exercise (or some other health or environmental variable), we can use various methods to determine what sequence variants (SNPs) exist for that particular gene. Then, we recruit volunteers to participate in our studies, use lab techniques to determine the sequence variation of that gene for each person, then study if the gene variant appears to affect that person's response to the stimulus. As you can see in our Publications section, we've begun to determine associations for some genes, but much work remains! One important point: although the news media might make it seem that there exists one gene for every health variable, that's just not so! While this may be the case for some rare diseases (muscular dystrophy, for example), diseases/disorders like breast cancer, diabetes, obesity, and cardiovascular disease are NOT determined by a single gene or gene sequence variant. Several genes and gene variants in addition to environmental stimuli will work together to determine a person's risk for various disorders. So when you hear the news media report on "a new gene" that explains a person's risk for something, use caution and remember that it's very likely only ONE OF MANY genes (plus the environment) that influence that trait! What is functional genomics? One other phrase that's received a lot of press in the scientific literature and we've actually chosen as our lab's title is "Functional Genomics." While "Genetics" encompasses the genes and gene sequence variants that we've described above, getting from a specific gene to a physical structure or function (or Health) is not that simple. Genes are located on DNA, DNA is transcribed into RNA, RNA is translated into a Protein, and then that Protein performs some function in the body. With about 23,000 genes and likely more than 150,000 proteins, there's a LOT that goes on in the body beyond just the gene sequence!! In other words, things are messy in the body and functional genomics takes a more global look at these factors in order to determine the CAUSE of an association between a gene variant and a health variable. Rather than just concentrating on the gene or the gene variant, we might look at the RNA for that gene, as well as the protein, in different environmental contexts in order to determine just how that gene might be functioning. In addition, functional genomics is concerned with the interactions of many genes, working in concert.