Description:

Abstract

Loss of skeletal muscle mass is associated with functional impairment, disability and increased mortality. Treatments to prevent muscle loss are an urgent unmet clinical need. Therefore, understanding the mechanisms that regulate muscle mass will provide potential clinical targets to improve quality of life and survival in healthy aging individuals, and those suffering from a wide variety of chronic disorders. In this seminar, I will present mechanistic evidence demonstrating that muscle anabolism is determined by the ability of the muscle to synthesize ribosomes. I will focus the discussion on the regulation of ribosomal DNA gene transcription by RNA Polymerase I, and will provide evidence for a role of the mechanistic target of Rapamycin (mTOR) in both transcriptional and epigenetic regulation of rDNA genes. I will also discuss how alterations in proteostasis negatively impact rDNA transcription and muscle mass. Recent findings from our laboratory implicate proteostatic stress as a critical modulator of nucleolar morphology via a p53-dependent response that suppresses rDNA transcription. This is highly significant for cancer therapies because alterations in proteostatic balance by anti-cancer drugs can have deleterious consequences on muscle anabolism, and thereby enhance muscle loss in already compromised clinical populations.

Speaker info

Dr. Nader received his PhD from the University of Illinois at Chicago (2003), and continued his training in Molecular Genetics at the Center for Genetic Medicine, Children's National Medical Center, Washington DC. Following his postdoctoral training, he established his laboratory at the Karolinska Institute in Stockholm, Sweden (2008) were he was affiliated with the Depts. of Clinical Neuroscience, Medicine and Physiology and Pharmacology. He is currently Associate Professor at the Dept. of Kinesiology and Huck Institutes of the Life Sciences at the Pennsylvania State University. His research continues to focus on the regulation of ribosome biogenesis and its role in the regulation of muscle growth by employing human, animal and cell models of muscle hypertrophy. Additionally, the lab seeks to decipher biomimicry approaches employed by hibernators to define novel strategies to preserve skeletal muscle mass.