Research Areas: Aging, Cell Biology, Diabetes, Metabolism, Molecular Biology, Muscle, Obesity
Our research focus is to understand how the Rb family of transcriptional repressors, p107 Rb and p130, intervenes in myogenic and adipogenic stem cell lineage commitment and differentiation. Studying this will lead to a greater insight on a wide range of health problems that will have an impact on almost everybody. For example; obesity develops with a negative energy balance that happens when energy intake outweighs energy expenditure. Adipose tissue plays a crucial role in the control of energy balance, with white adipose tissue that stores energy in the form of lipid and brown adipose tissue that metabolizes fatty acid to generate heat. In this regard, the RB family of transcriptional repressors acts as switches to adipogenic stem cells determining white versus brown adipocyte formation. Another example is the gradual decrease in skeletal muscle mass, strength, and endurance coupled with an ineffective response to tissue damage that occurs in ageing. Muscle fibre loss is counteracted by satellite cells, the adult myogenic stem cells that are capable of lifelong maintenance and repair. Satellite cells from aged individuals have a marked decrease in their proliferative and self renewal capacities that are influenced by the Rb family. Thus, understanding the function of the Rb family in stem cell fate will lead to a greater insight on ameliorating a wide range of health problems that will impact most of society from obesity that is linked to type II diabetes, cardiovascular disease and cancer to skeletal muscle weakness that occurs in ageing and many neuromuscular disorders.
Scimè A, Soleimani V , Gillespie MA, LeGrand F, Grenier G, Bevilacqua L, Harper ME, and Rudnicki MA. (2010). Oxidative status of muscle is determined by p107 regulation of PGC-1a. Journal of Cell Biology, Aug 23;190(4):651-62.
Scimè A, Desrosiers J, Palidwor GA, Trensz F, Caron AZ, Andrade-Navarro MA and Grenier G. (2010). Transcriptional profiling of skeletal muscle reveals factors that are necessary to maintain satellite cell integrity during aging. Mechanisms of Ageing & Development. Jan;131(1):9-20
Gillespie MA, Le Grand F, Scimè A, Kuang S, von Maltzahn J, Seale V, Cuenda A, Ranish J, and Rudnicki MA. (2009). p38?-dependent gene silencing restricts entry into the myogenic differentiation program. Journal of Cell Biology. Dec 28;187(7):991-1005.
Scimè A, AZ. Caron and Grenier, G. Advances in myogenic cell transplantation and skeletal muscle tissue engineering. (2009). Frontiers in Bioscience. Jan 1;14:3012-23.
Le Grand F, Jones AE, Seale V., Scimè A, and Rudnicki MA. (2009). Wnt 7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells. Cell Stem Cell. Cell Stem Cell. June 5;4:535-47.
Seale P, Bjork B, Yang W, Kajimura S, Kuang S, Scimè A, Devarakonda S, Conroe H, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, and Spiegelman BM. (2008). PRDM16 controls a brown fat/skeletal muscle switch. Nature. Aug 21;454(7207):961-7.
Scimè A, Li L, Ciavarra G, and Whyte P. (2008). Cyclin D1/cdk4 Interacts with E2F4/DP1 and Disrupts Its DNA Binding Capacity. Journal of Cellular Physiology. Mar;214(3):568-81.
Scimè A, and Rudnicki MA. Molecular-targeted therapy for duchenne muscular dystrophy: progress and potential. (2008). Molecular Diagnosis & Therapy. 12(2): 99-108.
Grenier G, Scimè A, Le Grand F, Asakura A, Perez-Iratxeta C, Andrade M, Labosky PA and Rudnicki MA. (2007). Resident Endothelial Precursors in Muscle, Adipose and Dermis Contribute to Post-Natal Vasculogenesis. Stem Cells. Dec;25(12):3101-10.
Pelka P, Scimè A, Mandalfino C, Joch M, Abdulla P, and Whyte P. (2007). Adenovirus E1A proteins direct subcellular redistribution of Nek9, a NimA-related kinase. Journal of Cellular Physiology. July;212(1):13-25.
Scimè A, and Rudnicki MA. Anabolic potential and regulation of muscle satellite cells. (2006). Current Opinion in Clinical Nutrition and Metabolic Care. May 9 (3): 214-19.
Scimè A, Grenier G, Huh MS, Gillespie MA, Bevilacqua L, Harper ME, and Rudnicki MA. (2005). Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1alpha. Cell Metabolism. Nov;2(5):283-95.
Rodier G, Makris C, Coulombe P, Scime A, Nakayama K, Nakayama KI, and Meloche S. (2005). p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2. Journal of Cell Biology. Jan 3;168(1):55-66.
Huh MS, Parker MH, Scimè A, Parks R, and Rudnicki MA.(2004). Rb is required for progression through myogenic differentiation but not maintenance of terminal differentiation. Journal of Cell Biology. Sep 13;166(6):865-76.
Seale P, Ishibashi J, Scimè A, and Rudnicki MA. (2004). Pax7 is necessary and sufficient for the myogenic specification of CD45+:Sca1+ stem cells from injured muscle. PLoS Biology. May;2(5):E130.