- Postdoctoral Fellow, Stanford University
- PhD, Toulouse University, 2011
MOLECULAR MECHANISMS OF CELLULAR REGENERATION
Contrary to human, some animals have the powerful capacity to fully regenerate damaged tissue and organs, including the nervous system. Our research focuses on the function of the stem cell population during tissue regeneration using the zebrafish as model organism. We take advantage of cutting-edge techniques in functional genetic analysis, by combining Tol2 transgenesis, Cre-Lox system for cell lineage tracing, single cell RNA-sequencing and CRISPR-Cas-9 genome editing method to characterize the mechanisms of cellular regeneration. Our work aims to identify regenerative factors involved in the stem cell activation and proliferation to open new paths for tissue regeneration in human.
Endogenous neural stem cell reprogramming for neuronal regeneration
In humans, olfactory or optic nerve injuries and associated neuronal degenerative diseases are often followed by permanent loss of smell or vision respectively. Unlike in humans, the zebrafish has the capacity to fully regenerate all neuronal subtypes and restore sensory functions after injury. Understanding the molecular mechanisms controlling retinal and olfactory neural stem cell function in zebrafish provides a starting point to design future strategies fully exploiting mammalian NSC potential for neuronal regeneration. We recently identified transcription factors involved in developmental and regenerative neurogenesis. This research project will study the capacity of these factors to activate/reprogram endogenous NSCs, allowing the formation of new neurons. We expect our discoveries to open new therapeutic strategies leading to the regeneration of neurons, limiting the negative impact of neurodegenerative diseases in humans.
Apelin signalling dependent muscle regeneration and rejuvenation
Progress in biomedicine has allowed people to live longer but with increasing age, elderly people often suffer from age-related diseases. The degenerative loss of muscle leading to muscular atrophy is called sarcopenia. The onset of sarcopenia has recently been linked to a decline in muscle regenerative capacity because of defects in muscle stem cell activation and proliferation. Recently, a small peptide highly conserved across the evolution, Apelin, has been shown to improve muscle stem cell proliferation, muscle regeneration and muscular function in aged animals. However, the molecular and cellular mechanisms underlying apelin regenerative function are largely unknown. This project will characterize the effects of apelin as an anti-aging and pro-regenerative signaling peptide and decipher the cell type specific functions of apelin in muscle homeostasis. We expect our findings to reveal molecular and cellular therapeutic targets to alleviate or reverse age-associated sarcopenia.
1 – Morphogenesis is transcriptionally coupled to neurogenesis during olfactory placode development.
Aiguillon R, Madelaine R, Guturu H, Link S, Dufourcq P, Lecaudey V, Bejerano G, Blader P, Batut J.
Development. 2020 Dec 21;147(24):dev192971. doi: 10.1242/dev.192971
2 – Neural signatures of sleep in zebrafish
Leung LC, Wang GX, Madelaine R, Skariah G, Kawakami K, Deisseroth K, Urban AE, Mourrain P.
Nature. 2019 Jul;571(7764):198-204.
3 – A screen for deeply conserved non-coding GWAS SNPs uncovers a MIR-9-2 functional mutation associated to retinal vasculature defects in human.
Madelaine R, Notwell JH, Skariah G, Halluin C, Chen CC, Bejerano G, Mourrain P.
Nucleic Acids Research. 2018 Mar 6. doi: 10.1093/nar/gky166.
4 – MicroRNA-9 Couples Brain Neurogenesis and Angiogenesis.
Madelaine R, Sloan SA, Huber N, Notwell JH, Leung LC, Skariah G, Halluin C, Paşca SP, Bejerano G, Krasnow MA, Barres BA, Mourrain P.
Cell Reports. 2017 Aug 15;20(7):1533-1542.
5 – Interhemispheric asymmetry of olfactory input-dependent neuronal specification in the adult brain.
Kishimoto N, Asakawa K, Madelaine R, Blader P, Kawakami K, Sawamoto K.
Nature Neuroscience. 2013 Jul;16(7):884-8.
6 – Partially redundant proneural function reveals the importance of timing during zebrafish olfactory neurogenesis.
Madelaine R, Garric.L, Blader P.
Development. 2011 Nov;138(21):4753-62.
Student projects using the zebrafish model organism are available to investigate the mechanisms of stem cell dependent regeneration.
Undergraduate will learn basic techniques of molecular and cellular biology, including transgenesis, CRISPR/Cas-9 genome editing, in situ hybridization and immunochemistry.
GSBSE grad students are accepted for rotation projects.
Contact us to discuss your research interest if you are considering joining the lab!