Shifeng Xue

Research Areas

• Developmental Biology, Epigenetics, Congenital Diseases, Molecular Biology.

Research Interests

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 development

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.

Awards

• 2018 Young Scientist Award, Singapore National Academy of Science
• 2018 Nominated Delegate to 68th Lindau Nobel Laureates Meeting
• 2015 Harold M. Weintraub Graduate Student Award
• 2009 National Science Scholarship (PhD)

Selected Publications

Khan H, Chong AEQ, Bilal M, Nawaz S, Abdullah, Abbasi S, Hussain A, Hussain S, Ullah I, Ali H, Xue S, Ahmad W (2021). Novel variants in the LRP4 underlying Cenani-Lenz Syndactyly syndrome. Journal of Human Genetics 2021 Dec. doi: 10.1038/s10038-021-00995-x.

Laberthonnière C, Novoa-Del-Toro EM, Chevalier R, Broucqsault N, Rao VV, Trani JP, Nguyen K, Xue S, Reversade B, Robin JD, Baudot A, Magdinier F (2021). AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome. Biomedicines 9(7):751.

Leppek K, Fujii K, Quade N, Susanto TT, Boehringer D, Lenaricic T, Xue S, Genuth NR, Ban N, Barna M (2020). Gene- and Species-Specific Hox mRNA Translation by Ribosome Expansion Segments. Molecular Cell 80(6):980-995

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 Research47(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 Chemistry293(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 Genetics100(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 Genetics49(2):249-255

*Co-first author

Xue S, Barna M (2015). Cis-regulatory RNA elements that regulate specialized ribosome activity. RNA Biology12(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. Nature517:33-38

Xue S, Barna M (2012). Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nature Reviews Molecular Cell Biology13(6):355-369