- Professor of Biochemistry
Investigator, Dalton Cardiovascular Research Center
PhD—University of California-Irvine
Teaching: Muscle biology
Adult skeletal muscle constitutes 40% of the body’s mass, and although it is comprised of multinucleated muscle fibers whose nuclei cannot divide, it retains the ability to repair and regenerate following exercise or disease-induced damage. This remarkable 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 of mature skeletal muscle cells. These cells are also responsible for the majority of post-birth skeletal muscle growth (maturation and hypertrophy) and adult skeletal muscle homeostasis. When activated in response to damage or exercise, satellite cells proliferate extensively, undergo self-renewal, and differentiate into new skeletal muscle fibers by fusing to each other or into the existing muscle fiber. Because satellite cells display lineage-specific differentiation (muscle cell) and self-renewal, two characteristics of stem cells, they can be considered adult resident stem cells. Self-renewal is an important property as it assures that the resident satellite cell pool is restored and available for subsequent cycles of damage-induced regeneration of skeletal muscle.
A major interest of the lab is the mechanism by which skeletal muscle satellite cell number is determined during skeletal muscle formation (myogenesis). Our recent studies have focused on the role of the TEAD-protein family of transcription factors in this process. Recently, we have found that constitutive overexpression of TEAD-1 (a TEA-domain transcription factor) in transgenic mice leads to a dramatic increase in skeletal muscle satellite cell number. These studies have also revealed activation of Notch signaling and attenuation of the Wnt signaling. These two signaling pathways have been strongly implicated in satellite cell maintenance and self-renewal in the adult. Our current studies are designed to identify potential intermediates connecting increased TEAD-1 expression in skeletal muscle fibers to increased satellite cell number, and altered Notch and Wnt signaling in satellite cells. 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.
R. W. Tsika, J. McCarthy, N. Karasseva, J., Y-s. Ou and G. L. Tsika. Divergence in Species and Regulatory Role of βMyosin Heavy Chain proximal promoter Muscle-CAT elements. Am. J. Physiol. Cell Physiol. 283:C1761-C1775, 2002.
N. Karasseva, G. Tsika, J. Ji, A. Zhang, X. Mao and R. W. Tsika. Transcription enhancer factor-1 binds multiple muscle MEF2 and A/T-rich elements during fast-to-slow skeletal muscle fiber type transitions. Mol.Cell Biol. 23(15):pp.5143-5164, 2003.
Parsons, S. A., D. P. Millay, B. J. Wilkins, O. F. Bueno, G. L. Tsika, J. R. Neilson, G. R. Crabtree, R. W. Tsika and J. D. Molkentin. Genetic loss of calcineurin blocks mechanical overload-induced skeletal muscle fiber-type switching but not hypertrophy. J. Biol. Chem. 279:26192-26200, 2004.
G. Tsika, J. Ji, and R. W. Tsika. Sp3 proteins negatively regulate βMyosin heavy chain gene expression during skeletal muscle inactivity. Mol. Cell Biol. 24(24):pp.10777-10791, 2004.
J. Ji, G. L. Tsika, H. Rindt, K. L.. Schreiber, J. J. McCarthy, R. J. Kelm, R. W. Tsika. (2007) Purα and Purβ collaborate with Sp3 to negatively regulate βMyHC gene expression during skeletal muscle inactivity. Mol. Cell Biol. 27: 1531-1543
Tsika R.W., Schramm C., Simmer G., Fitzsimons D.P., Moss R.L., 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
Richard W. Tsika, Lixin Ma, Izhak Kehat, Christine Schramm, Gretchen Simmer, Brandon Morgan, Deborah M. Fine, Laurin M. Hanft, Kerry S. McDonald, Jeffery D. Molkentin, Maike Krenz, Steve Yang, and Juan Ji
Tead-1 over-expression in the mouse heart promotes an age-dependent heart dysfunction J. Biol. Chem.( jbc.M109.063057First Published on March 1, 2010).