基本信息
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Career Trajectory
Bio
Medical School, University of Gothenburg, Medical Facility, Sweden; 1973。 Residency, Oskarshamn's Hospital in Surgery, Sweden; 1976, Sahlgrens University Hospital in Surgery, Sweden; 1979。 Fellowship, University of Cincinnati Medical Center in Surgery, Cincinnati, OH; 1986。
Vice Chairman, Research; Director, Endocrine Surgery at Beth Israel Deaconess Medical Center。 Harvard Medical Faculty Physicians (HMFP) at Beth Israel Deaconess Medical Center。 Professor, Surgery, Harvard Medical School。
uring the last several years, the research in our group has been focused on mechanisms regulating the catabolic response to sepsis and injury in skeletal muscle. Sepsis and injury (and a number of other conditions as well, including cancer, AIDS, uremia, and starvation) are associated with muscle wasting. The loss of muscle mass in these conditions mainly reflects activation of ubiquitin-proteasome-dependent and autophagy/lysosomal degradation of muscle proteins, although reduced protein synthesis contributes as well. The catabolic response in skeletal muscle has several significant clinical consequences, including muscle weakness and fatigue, delayed ambulation with risk of thromboembolic and pulmonary complications, and prolonged stay in the intensive care unit.
Recent research in our laboratory has focused on the role of different transcription factors regulating the expression of factors involved in the regulation of muscle proteolysis. Those transcription factors include NF-κB, C/EBPβ and δ, FOXO1 and 3a, and PPARß/δ.
In addition, our research has been focused on nuclear cofactors involved in the activation of transcription factors. In particular, our most recent efforts have examined the role of the histone acetyl transferase p300 and various histone deacetylases, such as SIRT1. Those studies have been important because they have highlighted the role of acetylation of transcription factors as well as other muscle proteins in the regulation of muscle mass. The role of acetylation and deacetylation in the regulation of muscle protein breakdown was summarized in a recent review from our laboratory (Metabolism 62:1-11, 2013). In this model, increased expression of p300 results in acetylation of transcription factors as well as other muscle proteins, making them susceptible to degradation. The state of hyperacetylation is further aggravated by reduced expression and activity of various histone-deacetylases, including SIRT1 (Figure 1). An important implication of these findings is that muscle wasting may be prevented and treated by agents that decrease p300 activity or by
agents that activate SIRT1 and other histone deacetylases.
Selected Publications
Alamdari N, Aversa Z, Castillero E, Gurav A, Petkova V, Tizio S, Hasselgren PO. Resveratrol prevents dexamethasone-induced expression of the muscle atrophy-related ubiquitin ligases atrogin-1 and MuRF1 in cultured myotubes through a SIRT1-dependent mechanism. Biochem Biophys Res Commun 2012;417:528-533.
Chamberlain W, Gonnella P, Alamdari N, Aversa Z, Hasselgren PO. Multiple muscle wasting-related transcription factors are acetylated in dexamethasone-treated muscle cells. Biochem Cell Biol 2012;90:200-208.
Alamdari N, Toraldo G, Aversa Z, Smith I, Castillero E, Renaud G, Qaisar R, Larsson L, Jasuja R, Hasselgren PO. Loss of muscle strength during sepsis is in part regulated by glucocorticoids and is associated with reduced muscle fiber stiffness. Am J Physiol Regul Integr Comp Physiol 2012;303:R1090-R1099.
Alamdari N, Aversa Z, Castillero E, Hasselgren PO. Acetylation and deacetylation – novel factors in muscle wasting. Metabolism 2013;62:1-11.
Castillero E, Alamdari N, Aversa Z, Gurav A, Hasselgren PO. PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting. PLoS One 2013;8(3):e59726.
Castillero E, Alamdari N, Lecker SH, Hasselgren PO. Suppression of atrogin-1 and MuRF1 prevents dexamethasone-induced atrophy of cultured myotubes. Metabolism Jul 15, 2013 (Epub ahead of print).
Research Interests
Papers共 262 篇Author StatisticsCo-AuthorSimilar Experts
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Chun Li,Betzamel Lopez,Scott Fligor,Jordan M. Broekhuis,Anthony Maeda,Sarah Duncan,Hao Wei Chen, Anam Choudhary, Simran Budwani,Per-Olof Hasselgren,Peter Mowschenson,Pavan S. Mallur,Benjamin C. James
Aaron M Cypess,Andrew P White,Cecile Vernochet,Tim J Schulz,Ruidan Xue,Christina A Sass, Tian Liang Huang,Carla Roberts-Toler,Lauren S Weiner,Cathy Sze,Aron T Chacko, Laura N Deschamps,Lindsay M Herder, Nathan Truchan,Allison L Glasgow,Ashley R Holman,Alina Gavrila,Per-Olof Hasselgren,Marcelo A Mori,Michael Molla,Yu-Hua Tseng
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Author Statistics
#Papers: 262
#Citation: 10831
H-Index: 49
G-Index: 101
Sociability: 7
Diversity: 0
Activity: 0
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