I graduated from the Lithuanian Sports University as a PE teacher in 1992, got a Masters degree in 1994 and was awarded a PhD from the same institution for the work on acute muscle adaptation to exercise using electrical stimulation in 1999. From 1999 to 2000, I was a Guest Researcher at the Department of Physiology and Pharmacology, Karolinska Institute (Advisor prof. Jan Henriksson) in Sweden working on the exercise effects on muscle signaling. From 2001 to 2003, I did a post doctoral work in muscle biology at the Pennsylvania State University (USA) and Uppsala University (Sweden; Advisor prof. Lars Larsson). From 2003 to 2007 I completed my second post doctoral position in quantitative genetics (Advisors Dr. David A. Blizard and Dr. George P. Vogler) at the Pennsylvania State University and worked there as a Research Associate until 2009. In March 2009, I took a post at the School of Medical Science, University of Aberdeen.
My research interests focus on the genetic mechanisms underlying variation in skeletal muscle mass and properties of muscle fibres that can affect muscle function. Muscle mass differs more than 2-fold between individuals even when sex and age are taken into account. The number of muscle fibres in homologous muscles can also differ by over 2-fold. Furthermore, skeletal muscle is not a homogeneous tissue but it is composed of a mixture of fast- and slow-twitch fibre types. The proportion of different types in homologous muscles also differs extensively between individuals. For instance, slow-twitch fibres in vastus lateralis can comprise from ~20% to ~80% of all fibres.
Why is this relevant? Skeletal muscle is responsible for a number of vital functions (respiration, locomotion, protection of bones and viscera, maintaining glucose homeostasis, etc) but also contributes significantly to energy expenditure. Reduced muscle mass leads to slower metabolism, a property associated with obesity. Studies have also shown that individuals with a lower proportion of type I fibres are at a greater risk of developing type II diabetes. Finally, aging is accompanied by deterioration of muscle mass and function. It is conceivable that individuals bestowed with lower muscle mass and smaller number of fibres would experience negative consequences of that more acutely.
Although some of this variability in muscle mass and fibre properties can be explained by the level of physical activity, genetic factors play a substantial role as well. However, the identity of specific genes determining differences in these traits remains largely unknown. We aim to address this question.
Figure 1. Soleus size differs ten times between two mouse strains. The difference is due to the number and cross-sectional area of the fibres constituting the muscle. Muscle cross sections were ATPase stained following acid preincubation. Dark stained fibres are type I, pale fibres are type IIA.
How is it done? We found that muscle mass can differ by ~10-fold, the number and cross-sectional area of muscle fibres by ~2-fold each between laboratory mouse strains (Figure 1). To search for genes underlying this variability in laboratory mice we use genome wide association studies (GWAS) approach that allows determination of the genomic position of causative genes (Figure 2).
How does that translate to humans? Myogenesis appears to be conserved across mammals with homologous genes having similar effects across different species. For example, the myostatin gene inhibits muscle growth in mice, dogs, sheep, cattle and even humans. Identification of muscle-affecting genes in the mouse model will offer a diagnostic target for alleles predisposing to a reduced muscle mass, as well as pharmacological targets for prevention and/or reversal of muscle mass loss in humans.
Figure 2. Genome-wide association scan for EDL muscle weight in CFW outbred mice. Analysis identified four loci, on chromosome 2 (two), 12 and 13, that affect muscle weight. Modified from Parker et al. 2016.
We are seeking enthusiastic and qualified candidates for projects focusing on validation of candidate genes and exploration of the mechanisms of their effects on muscle properties.
Dr. David Blizard, The Pennsylvania State University
Dr. Abraham Palmer, University of Chicago
Dr. Joe Angel, University of Texas
Dr. James Cheverud, Washington University in St. Louis
2007 – 2009 Dissection of Muscle Weight QTL via Congenic Strains (R03 AR052879); National Institute of Arthritis Musculoskeletal and Skin Diseases ($145,000 total cost); Role: PI
2009 - 2014 Genetic Variation of Muscle Mass (R01 AR056280); National Institute of Arthritis Musculoskeletal and Skin Diseases ($1,326,999 total cost); Role: Co-I
2009-2013 Genetic Mechanisms of Muscle Fibre Variation; European Commision – Marie Curie International Reintegration Grant (€87,500 total cost); Role: PI