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Academic Qualifications

PhD University of California, San Francisco

BS University of California, San Diego

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 68^th Lindau Nobel Laureates Meeting

2015 Harold M. Weintraub Graduate Student Award

2009 National Science Scholarship (PhD)

Selected Publications

1. Khan H, Koh G, Chong AEQ, Zahid M, Hussain S, Ali H, Ahmad W, Xue S (2023). A novel variant in AFF3 underlying isolated syndactyly. Clinical Genetics 103(3):341-345.

2. Xue S*, Ly TTN, Vijayakar RS, Chen J, Ng J, Mathuru AS, Magdinier F, Reversade B* (2022). HOX epimutations driven by maternal SMCHD1/ LRIF1 haploinsufficiency trigger homeotic transformations in genetically wildtype offspring. Nature Communications 13(3583):1–11. *co-corresponding authors

3. 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 67(5):253-259.

4. 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.

5. 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 Cell80(6):980-995

6. 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

7. 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

8. 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

9. 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

10. 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

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