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.
Porras, DP, Abbaszadeh, M. Bhattacharya D. D'Souza NC, Edjiu NR, Perry CGR and Scimè A. (2017). p107 determines a metabolic checkpoint required for adipocyte
lineage fates. Stem Cells. 2017 Ma; 35 (5): 1378-1391.
Bhattacharya D., Ydfors, M., Hughes MC, Norrbom J., Perry, C.G. and Scimè A. (2017).
Decreased transcriptional corepressor p107 is associated with exercise-induced
mitochondrial biogenesis in human skeletal muscle. Physiol Rep. 2017 Mar;5(5). pii;e13155.
Downey J., Lauzier D., Kloen P., Klarskov K., Richter M., Hamdy R., Faucheux N., Scimè A., Balg F. and Grenier G. (2015). Prospective heterotopic ossification progenitors in adult human skeletal muscle. Bone. Feb.71:164-70.
De Sousa M., Porras D.P., Seale P., Perry CGR and Scimè A. (2014). p107 is a crucial
regulator for determining the adipocyte lineage fate choices of stem cells. Stem Cells. May;32(5): 1323-36.
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
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, and Rudnicki MA. Molecular-targeted therapy for duchenne muscular dystrophy: progress and potential. (2008). Molecular Diagnosis & Therapy. 12(2): 99-108.