Education

Research Area

Transcriptional regulation in striated muscle during development, activity, and stress; transgenic mouse models.

Research Description

Molecular and cellular biology of muscle

Skeletal muscle constitutes 40% of the body’s mass and is designed to generate force for locomotor activity, postural maintenance, and plays an important role in the regulation of systemic energy balance.  Adult skeletal muscles are comprised primarily by four myofiber-types (myofiber = single cells; 3 fast-type and 1 slow-type). Notably, a given muscles fiber-type composition is not static, but instead, fiber-type composition is remarkably adaptable (fastàslow-twitch fibers or slowàfast-twitch fibers) to a broad spectrum of stimuli that include altered weight-bearing (increase load bearing, zero gravity), endocrine factors, altitude, endurance & resistance training, and diet (high fat vs high carbohydrate).  Furthermore, skeletal muscle can completely regenerate following damage due to various exercise regimes or in response to chronic disease states such as Duchene’s muscular dystrophy.  This property is primarily attributable to satellite cells which comprise a small population of quiescent mono-nucleated cells which first appear during late fetal life, and which reside between the basal lamina and the surface (sarcolemma) of mature skeletal muscle cells.  Satellite cells are considered adult skeletal muscle stem cells that are responsible for the majority of post-birth skeletal muscle growth (maturation and hypertrophy) and adult skeletal muscle homeostasis.

A major interest of my lab is to better understand the mechanism(s) by which skeletal muscle fiber type composition is regulated.  A second area if interest is how initial satellite cell number is determined during skeletal muscle formation (myogenesis).  Previous work has shown that slow-oxidative fibers are associated with more satellite cells per-unit length than are fast-glycolytic myofibers.  In this regard, our recent studies have provided strong evidence that the

TEA domain-1 (TEAD1) transcription factor participates in both slow oxidative fiber type gene expression and plays a role in satellite cell biology.

Our current studies are designed to identify potential signaling pathways connecting increased TEAD-1 expression in skeletal muscle to activation of genes encoding proteins typically restricted to slow-twitch fibers, as well as satellite cell numbers that exceed homeostatic numbers associated with slow-fibers.  We are also exploring whether the effects of TEAD-1 overexpression on satellite cell number and signaling is developmental-stage specific and/or restricted to specific muscle-fiber type, that is; fast-twitch or slow-twitch fibers.  Our goal is to provide insight into the temporal, spatial, and mechanistic requirements for satellite cell expansion during development, and maintenance and replacement during adult life and aging. To accomplish these goals my lab employs a combination of transgenic mouse models (Knock-out, knock-in, overexpression) coupled with transcriptome analysis (RNAseq, ChIP-Seq), and a standard array of histochemical, physiological and molecular biological techniques.

Selected Publications

Southard S, Kim JR, Low S, Tsika RW, Lepper C. (2016). Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency. Elife. 5. doi: 10.7554/eLife.15461. [PubMed]

Tsika RW, Ma L, Kehat I, Schramm C, Simmer G, Morgan B, Fine DM, Hanft LM, McDonald KS, Molkentin JD, Krenz M, Yang S, Ji J. (2010). TEAD-1 overexpression in the mouse heart promotes an age-dependent heart dysfunction. J Biol Chem. 285(18):13721-35. doi: 10.1074/jbc.M109.063057. [PubMed]

Shanely RA, Zwetsloot KA, Childs TE, Lees SJ, Tsika RW, Booth FW. (2009). IGF-I activates the mouse type IIb myosin heavy chain gene. Am J Physiol Cell Physiol. 297(4):C1019-27. doi: 10.1152/ajpcell.00169.2009. [PubMed]

Tsika RW, Schramm C, Simmer G, Fitzsimons DP, Moss RL, Ji J. (2008). Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype. J Biol Chem. 283(52):36154-67. doi: 10.1074/jbc.M807461200. [PubMed]

Tsika RW, McCarthy J, Karasseva N, Ou Y, Tsika GL. (2002). Divergence in species and regulatory role of beta -myosin heavy chain proximal promoter muscle-CAT elements. Am J Physiol Cell Physiol. 283(6):C1761-75. [PubMed]

Vyas DR, McCarthy JJ, Tsika GL, Tsika RW. (2001). Multiprotein complex formation at the beta myosin heavy chain distal muscle CAT element correlates with slow muscle expression but not mechanical overload responsiveness. J Biol Chem. 276(2):1173-84. [PubMed]

McCarthy JJ, Vyas DR, Tsika GL, Tsika RW. (1999). Segregated regulatory elements direct beta-myosin heavy chain expression in response to altered muscle activity. J Biol Chem. 274(20):14270-9. [PubMed]