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
exercise/physical activity can influence DNA itself (e.g., telomere
Stephen M. Roth, Ph.D., Associate Professor and Lab Director (website)
Andy Ludlow, PhD student
Lisa Guth, PhD student
Andrew Venezia, PhD student in the NACS program
Michael Marini, M.A. student
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 Postdoctoral Fellow, Univ.
Michigan School of Medicine
Ryan Sheppard, Ph.D., 2010 - currently research officer, U.S. Navy
Sarah Witkowski, Ph.D. (Post-doctoral fellow) - currently Assistant Professor, Univ. Massachusetts
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
Roth, S.M. (2007). Genetics
Primer for Exercise Science and Health. Champaign IL: Human
Kinetics. ISBN: 0736063439. (see
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)
for recent publications
Recent, representative publications (* indicates student advisee):
- Roth, S.M.†, S. Walsh*, D. Liu*, E.J. Metter, L.
Ferrucci, B.F. Hurley. The ACTN3 R577X nonsense allele is
under-represented in elite-level strength athletes. European Journal of
Human Genetics, 16: 391-394, 2008. (PMCID: PMC2668151)
- Charbonneau, D.E.*, E.D. Hanson, A.T. Ludlow*, M.J.
Delmonico, B.F. Hurley, S.M. Roth†. ACE genotype and the muscle
hypertrophic and strength responses to strength training. Medicine and
Science in Sports and Exercise, 40: 677-683, 2008.
- Deeny, S.P., D. Poeppel, J.B. Zimmerman, S.M. Roth,
J. Brandauer, S. Witkowski, J.W. Hearn, A.T. Ludlow*, J.L.
Contreras-Vidal, J. Brandt, B.D. Hatfield†. Exercise, APOE, and working
memory: MEG and behavioral evidence for benefit of exercise in epsilon4
carriers. Biological Psychology, 78: 179-187, 2008.
- Liu, D.*, E.J. Metter, L. Ferrucci, S.M. Roth†. TNF
promoter polymorphisms associated with muscle phenotypes in humans.
Journal of Applied Physiology, 105: 859-867, 2008. (PMCID: PMC2536817)
- Roth, S.M.†, S.M. Williams, L. Jiang, K.S. Menon,
J.J. Jeka. Susceptibility genes for gentamicin-induced vestibular
dysfunction. Journal of Vestibular Research, 18: 59-68, 2008. (PMCID:
- Roth, S.M. Functional genomics and the path to
personalized medicine. Commentary article for Exercise and Sport
Sciences Reviews, 36: 49-50, 2008.
- Roth, S.M. Viewpoint: Perspective on the future use
of genomics in exercise prescription. Unsolicited commentary for
Journal of Applied Physiology, 104: 1243-1245, 2008. [See associated
invited commentaries on pages 1246-1253 in this same issue.]
- Ludlow, A.T.*, J.B. Zimmerman, S. Witkowski, J.W.
Hearn, B.D. Hatfield, S.M. Roth†. Relationship between physical
activity, telomere length, and telomerase activity. Medicine and
Science in Sports and Exercise, 40: 1764-1771, 2008. (PMCID:
- Walsh, S.*, D. Liu*, E.J. Metter, L. Ferrucci, S.M.
Roth†. ACTN3 genotype is associated with muscle phenotypes in women
across the adult age span. Journal of Applied Physiology, 105:
1486-1491, 2008. (PMCID: PMC2584847)
- Delmonico, M.J., J.M. Zmuda, B.C. Taylor, J.A.
Cauley, T.B. Harris, T.M. Manini, A. Schwarz, R. Li, S.M. Roth, B.F.
Hurley, D.C. Bauer, R.E. Ferrell, A.B. Newman†. Association of the
ACTN3 genotype and physical functioning with age in older adults.
Journal of Gerontology Medical Sciences, 63A, 1227-1234, 2008.
- Fenty-Stewart, N., J.Y. Park, S.M. Roth, J.M.
Hagberg, S. Basu, R.E. Ferrell, M.D. Brown†. Independent and combined
influence of AGTR1 variants and aerobic exercise on oxidative stress in
hypertensives. Blood Pressure, 18: 204-212, 2009.
- Bray, M.S., J.M. Hagberg, L. Pérusse,
Rankinen, T., S.M. Roth, B. Wolfarth, C. Bouchard†. The human gene map
for performance and health-related fitness phenotypes: the 2006-2007
update. Medicine and Science in Sports and Exercise, 41: 34-72, 2009.
- Faulkner, K.A., J.A. Cauley, S.M. Roth, C.
Kammerer, K. Stone, T.A. Hillier, K.E. Ensrud, M. Hochberg, M.C.
Nevitt, J.M. Zmuda†. Familial resemblance and shared latent familial
variance in recurrent fall-risk in older women. Journal of Applied
Physiology, 108: 1142-1147, 2010.
- Rankinen, T., S.M. Roth, M.S. Bray, R. Loos, L.
Perusse, B. Wolfarth, J.M. Hagberg, C. Bouchard. Advances in exercise,
fitness and performance genetics. Medicine and Science in Sports and
Exercise, 42(5): 835-846, 2010.
- Hanson, E.D.*, A.T. Ludlow*, A.K. Sheaff, J. Park, S.M. Roth†. ACTN3 genotype does not influence muscle power. International Journal of Sports Medicine, 31: 834-838, 2010.
- Lima, R.M.*, T.K.M. Leite, R.W. Pereira, H.T. Rabelo, S.M. Roth, R.J. Oliveira†. ACE and ACTN3 genotypes in older women: muscular phenotypes. International Journal of Sports Medicine, 32: 66-72, 2011.
- Windelinckx, A., G. De Mars, W. Huygens, M. Peeters, B. Vincent, C. Wijmenga, D. Lambrechts, C. Delecluse, S.M. Roth, E.J. Metter, L. Ferrucci, J. Aerssens, R. Vlietinck, G. Beunen, M. Thomis†. Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene. European Journal of Human Genetics, 19: 208-215, 2011.
- McKenzie, J.A., S. Witkowski, A.T. Ludlow*, S.M. Roth, J.M. Hagberg†. AKT1 G205T genotype influences obesity-related metabolic phenotypes and their responses to aerobic exercise training in older Caucasians. Experimental Physiology, 96.3: 338-347, 2011.
- Ludlow. A.T, S.M. Roth. Physical activity and telomere biology: exploring the link with aging-related disease prevention. Journal of Aging Research, vol. 2011, Article ID 790378, 12 pg, 2011. doi:10.4061/2011/790378
- Hagberg, J.M., T. Rankinen, R.J.F. Loos, L. Perusse, S.M. Roth, B. Wolfarth, C. Bouchard. Advances in exercise, fitness, and perforfdmance genomics in 2010. Medicine and Science in Sports and Exercise, 43(5): 743-752, 2011
Currently Funded Grants:
Principal Investigator with Spangenburg (Co-I): HD062868: Role of
maternal exercise environment on transgenerational offspring health,
R21 for NIH/NICHD. Sept. 2010-2012.
Co-Investigator with Haufler (PI): Samueli Foundation: Superior
performance under pressure. Apr 10-Apr 11.
PI, subcontract; Co-Investigator with Brown (PI): HL085497: Genetics of
in vivo and in
vitro endothelial function, R01 for NIH/NHLBI, June 2007-2012.
Co-Mentor with Hagberg (PI): AG00268: Predoctoral training in exercise
physiology and aging, T32, NIH/NIA Institutional Predoctoral Training
Grant, May 2009-2013.
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
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.
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
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
How do we study the impact of Genetics
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
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.