Department of Biological Sciences
National University of Singapore
14 Science Drive 4
PhD University of California, San Francisco
BS University of California, San Diego
Developmental Biology, Epigenetics, Congenital Diseases, Molecular Biology.
During development, cells need to know where to go and what to become. Genes need to turn on and off at the right time. This is important as de-repression of unwanted genes during embryogenesis can cause birth defects. Our lab focuses on epigenetic repression and regulation.
SMCHD1 and congenital diseases
SMCHD1 is an evolutionarily conserved protein that mediates gene repression. In humans, mutations in SMCHD1 cause two distinct diseases with different timings of onset and affecting different tissues. Loss of function mutations in SMCHD1 is known to in part cause a muscle degenerative disorder known as facioscapulohumeral muscular dystrophy (FSHD). Missense mutations in the extended ATPase domain cause Bosma arhinia microphthalmia syndrome (BAMS) where patients are born without a nose. Using cells and animal models, we aim to understand how mutations in SMCHD1 can cause different outcomes.
Craniofacial anomalies are amongst the most common birth defects. We study the two cell types that give rise to most cells in the face, neural crest and cranial placodes. Through differentiation into these cell types from pluripotent stem cells, we aim to understand the genes and pathways involved in forming these lineages and what goes wrong in diseases.
Novel epigenetic repressors
Only a small fraction of the genome is active at any one point. Much of the genome, such as transposable elements, need to be silenced at all times. We aim to perform genome-wide functional screens to identify novel epigenetic repressors.
2018 Young Scientist Award, Singapore National Academy of Science
2015 Harold M. Weintraub Graduate Student Award
Dion C, Roche S, Laberthonnière C, Broucqsault N, Mariot V, Xue S, Gurzau A, Nowak A, … , Murphy J, Dejardin J, Blewitt M, Reversade B, Robin J, Magdinier F (2019). SMCHD1 is involved in de novo methylation of the DUX4-encoding D4Z4 macrosatellite. Nucleic Acids Research 47(6):2822-2839
Gurau AD*, Chen K*, Xue S, Dai W, Lucet IS, Ly TTN, Reversade B, Blewitt ME, Murphy JM (2018). FSHD2- and BAMS-associated mutations confer opposing effects on SMCHD1 function. Journal of Biological Chemistry 293(25):9841-9853
Xue S*, Maluenda J*, Marguet F*, … , Reversade B, Melki J (2017). Loss-of-function mutations in LGI4, a secreted ligand involved in Schwann cell myelination, are responsible for arthrogryposis multiplex congenital. American Journal of Human Genetics 100(4):659-665
Gordon CT*, Xue S*, Yigit G*, Filali H*, Chen K*, … , Lyonnet S, Magdinier F, Javed A, Blewitt ME, Amiel J, Wollnik B, Reversade B (2017). De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development. Nature Genetics 49(2):249-255
Xue S, Barna M (2015). Cis-regulatory RNA elements that regulate specialized ribosome activity. RNA Biology 12(10):1083-7
Xue S, Tian S, Fujii K, Kladwang W, Das R, Barna M (2015). RNA regulons in Hox 5’UTRs confer ribosome specificity to gene regulation. Nature 517:33-38
Xue S, Barna M (2012). Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nature Reviews Molecular Cell Biology 13(6):355-369
Kondrashov N, Pusic A, Stumpf CR, Shimizu K, Hsieh AC, Xue S, Ishijima K, Shiroishi T, Barna M (2011). Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell 145(3):383-97