Interdisciplinary Life Science - PULSe Great research is a matter of choice

Shihuan Kuang

Shihuan Kuang Profile Picture

Professor, Department of Animal Sciences & Center for Cancer Research

Contact Info:


Training Group(s):
Molecular Signaling and Cancer Biology
Biomolecular Structure and Biophysics

Current Research Interests:

Adult stem cell biology

A balance between self-renewal and differentiation is crucial for stem cell maintenance and tissue homeostasis. However, mechanisms governing stem cell fate are poorly understood. One goal of our research is to address this question using muscle satellite cells as a model system. Several recent studies have revealed an important role of asymmetric division in satellite cell self-renewal. We are particularly interested in the mechanisms involved in the cell fate decision of muscle satellite cells.

Muscle development, regeneration and neuromuscular diseases

Skeletal muscles have a remarkable regenerative capacity due to myogenic differentiation of satellite cells. We have recently shown that the satellite cell niche contains heterogeneous subpopulations of committed myogenic progenitors and non-committed stem cells. This hierarchical composition of readily differentiating progenitors and self-renewable stem cells assures the extraordinary regenerative capacity of skeletal muscles while maintaining a sustainable pool of satellite cells. One focus of my lab is to explore the signaling mechanisms that differentially regulate these subpopulations of satellite cells and how such mechanisms are employed in muscle regeneration.

Many degenerative neuromuscular diseases are due to defective motor neurons and/or muscle fibers. One potential treatment of these pathological conditions is stem cell-based therapy. Currently, several limitations, including poor survival, poor migration and host rejection, are associated the use of satellite cells and other muscle stem cells in the treatment of muscular diseases. We are exploring the utility of muscle stem cells in the treatment of muscular dystrophy and other neuromuscular diseases.

Adipose tissue plasticity and obesity

Adipose tissue contains white, beige (also called brite) and brown adipocytes. White adipocytes store lipids and their excessive accumulation are associated with obesity. Beige and brown adipocytes can break down and utilize lipids to generate heat, and are associated with leaner body mass. We are particularly interested in the lineage origin of the three types of adipocytes and their plasticity (interconversion). Understanding the molecular mechanisms that regulate adipose tissue plasticity is key to the development of therapeutic approached to combat the rising epidemics of obesity and its associates metabolic syndromes.

Muscle-fat interaction

We have recently shown that muscle interstitial adipocytes are required for efficient regeneration of injured muscles. Meanwhile, we found that muscle-specific cytokines (myokines) can regulate the plasticity (for example conversion of white to beige adipcytes) and gene expression of adipose tissues. We are interested in understanding the molecular basis of muscle-fat interaction with ultimate goals to improve the regenerative capacity of skeletal muscles and prevent/treat obesity and diabetes.

Selected Publications:

Selected from 80+ peer-reviewed publications

Shan T, Zhang P, Jiang Q, Xiong Y, Kuang S. 2016. Adipocyte-specific deletion of mTOR inhibits adipose development and causes insulin resistance. Diabetologia. 59(9): 1995-2004.

Nie Y, Sato Y, Wang C, Yue F, Kuang S*, Gavin TP*. 2016. Impaired exercise tolerance in miR-133a deficient mice through AKT mediated inhibition of mitochondrial biogenesis. FASEB J. PMID: 27458245

Shan T, Xiong Y, Zhang P, Li Z, Jiang Q, Bi P, Yue F, Yang G, Wang Y, Liu X, Kuang S. 2016. Lkb1 controls brown fat growth and thermogenesis through regulating intracellular localization of CRTC3. Nat Commun. 7:12205. doi: 10.1038/ncomms12205.

Bi P, Yue F, Karki A, Castro B, Wirbisky SE, Wang C, Durkes A, Elzey BD, Andrisani OM, Bidwell CA, Freeman JL, Konieczny SF, Kuang S. 2016. Notch activation drives adipocyte dedifferentiation and tumorigenic transformation in mice. J Exp Med. 213(10), doi: 10.1084/jem.20160157

Kuang S, Charge SB, Seale P, Huh M, Rudnicki MA. 2006. Distinct roles for Pax7 and Pax3 in adult regenerative myogenesis. J Cell Biol 172:103-13.

Kuang S, Kuroda K, Le Grand F, Rudnicki MA. 2007. Asymmetric self-renewal and commitment of satellite stem cells in muscle. Cell 129:999-1010. Featured by "Preview" in Cell 129(5):859-61.

Kuang S, Rudnicki MA. 2008. The emerging biology of satellite cells and their therapeutic potentials. Trends Mol Med 14: 82-91.

Kuang S, Gillespie M, Rudnicki MA. 2008. Niche regulation of muscle satellite cell self-renewal and differentiation. Cell Stem Cell 2: 22-31.

Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe H, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM. 2008. PRDM16 Controls a Brown Fat/Skeletal Muscle Switch. Nature 454:961-7 (Article, Cover Picture). Science magazine’s top 10 breakthroughs of 2008

Rudnicki MA, Le Grand F, McKinnell I, Kuang S. 2008. The molecular regulation of muscle stem cell function. Cold Spring Harb Symp Quant Biol 73:323-31.

Waddell JN, Zhang P, Wen Y, Gupta SK, Yevtodiyenko A, Schmidt JV, Bidwell CA, Kumar A, Kuang S. 2010. Dlk1 is necessary for proper skeletal muscle development and regeneration. Plos ONE 5(11): e15055.

Dahiya S, Bhatnagar S, Jiang C, Paul PK, Kuang S, Kumar A. 2011. Elevated levels of active matrix metalloproteinase-9 cause hypertrophy and limit fibrosis in skeletal muscle of normal and dystrophin-deficient mdx mice. Hum Mol Genet 20:4345-59.

Angione AR, Jiang C, Pan D, Wang YX, Kuang S. 2011. PPARd regulates satellite cell proliferation and skeletal muscle regeneration. Skelet Muscle 1(1):33.

Liu W, Liu Y, Lai X, Kuang S. 2012. Intramuscular adipose is derived from a non-Pax3 lineage and required for efficient regeneration of skeletal muscles. Dev Biol 361(1):27-38.

Wen Y, Bi P, Liu W, Asakura A, Keller C, Kuang S. 2012. Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells. Mol Cell Biol 32(12):2300-11.

Liu W, Wen Y, Bi P, Lai X, Liu XS, Liu X, Kuang S. 2012. Hypoxia promotes satellite cell self-renewal and enhances the efficiency of myoblast transplantation. Development 139(16):2857-65.

Wang M, Yu H, Kim YS, Bidwell CA, Kuang S. 2012. Myostatin facilitates slow and inhibits fast myosin heavy chain expression during myogenic differentiation. Biochem Biophys Res Commun 426(1):83-8.

Hindi SM, Paul PK, Dahiya S, Mishra V, Bhatnagar S, Kuang S, Choi Y, Kumar A. 2012. Reciprocal Interaction between TRAF6 and Notch signaling regulates adult myofiber regeneration upon injury. Mol Cell Biol 32(23):4833-45.

Shan T, Liu W, Kuang S. 2013. Fatty acid binding protein 4 expression marks a population of adipocyte progenitors in white and brown adipose tissues. FASEB J 27(1):277-87.

Shan T, Liang X, Bi P, Kuang S. 2013. Myostatin knockout drives browning of white adipose through activating the AMPK-PGC1a-Fndc5 pathway in muscle. FASEB J 27(5):1981-9.

Liu W, Bi P, T Shan, X Yang, Yin H, Wang YX, Liu N, Rudnicki MA, Kuang S. 2013. miR-133a regulates adipocyte browning in vivo. Plos Genet 9(7): e1003626.

Liu W, Kuang S. 2013. miR-133 links to energy balance through targeting Prdm16. J Mol Cell Biol. 5(6):432-4.

Shan T, Liang X, Bi P, Zhang P, Liu W, Kuang S. 2013. Distinct populations of adipogenic and myogenic Myf5-lineage progenitors in white adipose tissues. J Lipid Res 54(8):2214-24.

Liu W, Shan T, Yang X, Liu Y, Liang X, Zhang P, Liu X, Kuang S. 2013. A heterogeneous lineage origin underlies phenotypic and molecular differences of white and beige adipocytes. J Cell Sci 126(16):3527-32.

Ogura Y, Mishra V, Hindi SM, Kuang S, Kumar A. 2013. Proinflammatory cytokine TWEAK suppresses satellite cell self-renewal through inversely modulating Notch and NF-kappa B signaling pathways. J Biol Chem 288(49):35159-69.

Jiang C, Wen Y, Kuroda K, Hannon K, Rudnicki MA, Kuang S. 2014. Notch signaling deficiency underlies age-dependent depletion of satellite cells in muscular dystrophy. Dis Model Mech 7(8):997-1004.

Bi P, Shan T, Liu W, Yue F, Yang X, Liang XR, Wang J, Li J, Carlesso N, Liu X, Kuang S. 2014 Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity. Nat Med. 20(8): 911-8. Featured by "News and Views" in Nature Medicine 20(8): 811-2 and "Editors' Choice" in Science Signaling 7:ec211.

Shan T, Zhang P, Liang X, Bi P, Kuang S. 2014. Lkb1 is indispensable for skeletal muscle development, regeneration and satellite cell homeostasis. Stem Cells 32(11):2893-907.

Zhang P, Shan T, Liang X, Deng C, Kuang S. 2014. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice. Biochem Biophys Res Commun. 452(1):53-9.

Shan T, Zhang P, Bi P, Kuang S. 2015. Lkb1 deletion promotes ectopic lipid accumulation in muscle progenitor cells and mature muscles. J Cell Physiol. 230(5):1033-41.

Wang JH, Wang Q, Wang C, Reinholt B, Grant AL, Gerrard DE, Kuang S. 2015. Heterogeneous activation of a slow myosin gene in proliferating myoblasts and differentiated single myofibers. Dev Biol. 402(1):72-80.

 Bi P, Kuang S. 2015. Notch signaling as a novel regulator of energy metabolism. Trends Endocrinol Metab. 26(5):248-255.

Wang C, Liu W, Liu Z, Chen L, Liu X, Kuang S. 2015. Hypoxia inhibits myogenic differentiation through p53-dependent induction of Bhlhe40. J Biol Chem. 290(50):29707-16.

Jiang C, Kuang L, Merkel MP, Yue F, Cano-Vega MA, Narayanan N, Kuang S*, Deng M*. 2015. Biodegradable polymeric microsphere-based drug delivery for inductive browning of fat. Front Endocrinol. 6: 169. doi: 10.3389/fendo.2015.00169.

Jiang C, Wang JH, Yue F, Kuang S. 2016. The brain expressed x-linked gene 1 (Bex1) regulates myoblast fusion. Dev Biol. 409(1): 16-25.

Shan T, Zhang P, Xiong Y, Wang Y, Kuang S. 2016. Lkb1 deletion upregulates Pax7 expression through activating Notch signaling pathway in myoblasts. Int J Biochem Cell Biol. 76(2016): 31–38.

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