Events

Clara De Palma biosketch

Skeletal muscles comprise approximately 40 % of total body weight, contain 50–75 % of all body proteins and contribute significantly to multiple bodily functions. This tissue architecture is characterized by a very particular arrangement of muscle fibers (myofibers) and associated support tissues (blood vessels; stroma).
Myofibers can regenerate following injury. This is due to the presence of resident stem cells called satellite cells (MuSCs). When activated by extrinsic stimuli, satellite cells proliferate and differentiate into new myofibers.
Our previous studies, and those of others, highlighted that many signaling cascades control muscle tissue repair. We thus focus on signaling pathways deployed during regeneration and aim to push forward the frontier of our current knowledge on adult myogenesis.
In an original approach, our team utilize conditional mouse models, transcriptomics and epigenomics, as well as single-cell analyses. Our research will identify specific targets for therapeutic development, which will be the basis for future translational research to treat muscular dystrophies

Neuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins (RBPs) play a key role in this regulation. However, while their action on individual mRNAs has been explored in depth, the mechanisms used to coordinate expression of the gene programs shaping neuronal morphology are poorly understood. To address this, we analysed how the RBP IMP1 (IGF2BP1), an essential developmental factor, selects and regulates its RNA targets during the differentiation of human neurons. We performed a combination of system-wide and molecular analyses, revealing that IMP1 developmentally transitions to and directly regulates the expression of mRNAs encoding essential regulators of the microtubule network, a key component of neuronal morphology. Furthermore, we showed that m6A methylation drives the selection of specific IMP1 mRNA targets and their protein expression during the developmental transition from neural precursors to neurons, providing a molecular principle for the onset of target selectivity.

Cristiana Perrotta Biography

My scientific path started with the characterization of anabolic and catabolic circulating factors that associate with muscle wasting in several animal models of cancer cachexia, finding reduced IGF-1 and increased myostatin as common signs induced by tumor growth. My research provided the first evidence that tumor growth impairs the myogenic potential and that ERK inhibition rescues the myogenic capacity and partially prevents muscle depletion in tumor hosts. In parallel, I described the specific effects of tumor growth on muscle mitochondria and the ability of training exercise to revert such alterations in order to move the scientific interest from muscle mass to muscle quality, function, and metabolism. The current focus of my research has moved from a muscle centric perspective to a broad host metabolism approach, in order to understand cancer as a systemic host disease.

Johan Auwerx is using systems biology and genetics approaches to understand the communication between the mitochondria and the nucleus. His work is relevant for the areas of transcription, mitochondria, metabolism, and aging. His research spurred the development of new drugs, such as PPAR agonists, Urolithins, PARP and ACMSD inhibitors and other NAD⁺ boosters for the treatment of age-related metabolic, cardio-vascular and neuro-muscular diseases. Johan Auwerx was elected as a member of EMBO in 2003 and has received many international scientific prizes. He is the founder of several biotech companies.

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