Associate Professor of Genomics and Precision Medicine
Associate Professor of Pediatrics (Secondary)
Office Phone: 202-884-6094
Department: Genomics and Precision Medicine
- B.V.M., National Taiwan University, 1991
- M.S., National Taiwan University, 1993
- PhD, University of Missouri, Columbia, 1998
Selected from 60, Peer-reviewed 58:
- Chen, Y.-W., Zhao, P., Borup, R. & Hoffman, E. P. (2000) Expression profiling in the muscular dystrophies: Identification of novel aspects of molecular pathophysiology. J Cell Biol 151(6):1321-36.
- Chen, Y.-W., Nader, G. A., Baar, K. R., Fedele, M. J., Hoffman, E. P. & Esser, K. A. (2002) Response of muscle to acute exercise defined by transcriptional and translational profiling. J Physiol 545(1):27-41.
- Winokur, S. T., Chen, Y.-W., Masny, P. S., Martin, J. H., Ehmsen, J. T., Tapscott, S. J., van der Maarel, S. M., Hayashi, Y. & Flanigan, K. M. (2003) Expression profiling of FHSD muscle supports a defect in specific stages of myogenic differentiation. Hum Mol Genet 12(22): 2895-2907.
- Chen, Y.-W., Nagaraju, K., Bakay, M., McIntyre, O., Rawat, R., Shi, R. & Hoffman, E. P. (2005) Early onset of inflammation and later involvement of TGFβ in Duchenne muscular dystrophy. Neurology 65(6):826-34.
- Chen, Y.-W., Gregory, C. M., Scarborough, M. T., Shi, R., Walter, G. A. & Vandenborne, K. (2007) Transcriptional pathways associated with skeletal muscle disuse atrophy in humans. Physiol Genomics 31(3):510-20.
- Dixit, M., Ansseau, E., Tassin, A., Winokur, S., Shi, R., Qian, H., Sauvage, S., Matteotti, C., van Acker, A. M., Leo, O., Figlewicz, D., Barro, M., Laoudj-Chenivesse, D., Belayew, A., Coppee, F. & Chen, Y.-W. (2007) DUX4, a candidate gene of FSHD, encodes a transcriptional activator of PITX1. Proc Natl Acad Sci USA. 104(46):18157-62.
- Alger, H.M., Raben, N., Pistilli, E., Francia, D.L., Rawat, R., Getnet, D., Ghimbovschi, S., Chen, Y.-W., Lundberg, I.E., Nagaraju, K. (2011).The role of TNF-alpha-related apoptosis-inducing ligand (TRAIL) in mediating autophagy in myositis: A potential non-immune mechanism of muscle damage. Arthritis & Rheumatism, 63 (11), 3448-3457.
- Kostek, M. C., Nagaraju, K., Pistilli, E., Sali, A., Lai, S.-H., Gordon, B. S. and Chen, Y.-W. (2012). IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse. BMC Musculoskeletal Disorders. 13(1): 106.
- Sharma, V., Harafuji, N., Belayew, A., Chen, Y.-W. (2013) DUX4 differentially regulates transcriptomes of human rhabdomyosarcoma and mouse C2C12 cells. PLoS One. 8(5):e64691.
- Narola, J., Pandey S.N., Glick A., Chen, Y.-W. (2013) Conditional expression of TGFβ1 in skeletal muscles causes endomysial fibrosis and myofibers atrophy. PLoS One. 8(11):e79356.
- Harafuji, N., Schneiderat, P., Walter, M.C. and Chen, Y.-W. (2013) miR-411 is up-regulated in FSHD myoblasts and suppresses myogenic factors. Orphanet J Rare Dis 8(1):55.
- Pandey, S.N, Lee, Y.C., Yokota, T., Chen, Y.-W. (2014) Morpholino treatment improves muscle function and pathology of pitx1 transgenic mice. Mol Ther. 22(2):390-6.
- Burniston, J.G., Kenyani, J., Gray, D., Guadagnin, E., Jarman, I.H., Cobley, J.N., Cuthbertson, D.J., Chen, Y.-W., Wastling, J.M., Lisboa, P.J., Koch, L.G., and Britton, S.L. (2014) Conditional independence mapping of DIGE data reveals PDIA3 protein species as key nodes associated with muscle aerobic capacity. J Proteomics. 106:230-45.
- Dadgar, S., Wang, Z., Johnston, H., Kesari, A., Nagaraju, K., Chen, Y.-W., Hill, D.A., Partridge, T.A., Giri, M., Freishtat, R.J., Nazarian, J., Xuan, J., Wang, Y. and Hoffman, E.P. (2014) Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy. J Cell Biol. 207(1):139-58.
- Pandey, S. N., Khawaja, H. and Chen, Y.-W. (2015). Culture Conditions Affect Expression of DUX4 in FSHD Myoblasts. Molecules 20, 8304-8315.
- Guadagnin, E., Narola, J., Bönnemann, C.G., Chen, Y.-W. (2015) Tyrosine 705 phosphorylation of STAT3 is associated with phenotype severity in TGFβ1 transgenic mice. Biomed Res Int. 2015;2015:843743.
- Baligand, C., Chen, Y.-W.*, Ye, F., Pandey, S., Lai, S.-H., Liu, M. Vandenborne, K. (2015). Transcriptional pathways associated with skeletal muscle changes after spinal cord injury and treadmill locomotor training. Biomed Res Int. 2015;2015:387090.
- Munters, L., Loell, I., Ossipova, E., Raouf, J., Dastmalchi, M., Lindroos, E., Chen, Y.-W., Esbjörnsson, M., Korotkova, M., Alexanderson, H., Nagaraju, K., Crofford, L., Jakobsson, P-J., Lundberg, I. E. (2016) Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients with Myositis. Arthritis Rheumatol. 2016 Jul;68(7):1738-50.
- Loell, I. Raouf, J., Chen, Y.-W., Shi, R., Nennesmo, I., Alexanderson, H., Dastmalchi, M., Nagaraju, K., Korotkova, M., Lundberg, I. E. (2016) Effects on muscle tissue remodeling and lipid metabolism in muscle tissue from adult patients with polymyositis or dermatomyositis treated with immunosuppressive agents. Arthritis Res Ther. 18: 136.
- Sharma, V., Pandey, S.N, Khawaja, H., Brown K.J., Hathout, Y. and Chen, Y.-W. (2016). PARP1 differentially interacts with promoter region of DUX4 gene in FSHD myoblasts. J Genet Syndr Gene Ther. 7(4).
- Chen, Y.-W., Gregory, C., Ye, F., Harafuji, N., Lott, D., Lai, S.-H., Mathur, S., Scarborough, M., Gibbs, P., Baligand, C. & Vandenborne, K. (2017) Molecular signatures of differential responses to exercise trainings during rehabilitation, Biomedical Genetics and Genomics. Volume 2(1)
- Mah, J. and Chen, Y.-W. (2017) A pediatric review of facioscapulohumeral muscular dystrophy. Journal of Pediatric Neurology. DOI: 10.1055/s-0037-1604197.
- Boehler, J.F. Hogarth, M.W., Barberio, M.D., Novak, J.S., Ghimbovschi, S., Brown, K.J., Alemo Munters, L., Loell, I., Chen, Y.-W., Gordish-Dressman, H., Alexanderson, H., Lundberg, IE, Nagaraju, K. (2017) Effect of endurance exercise on microRNAs in myositis skeletal muscle-A randomized controlled study. PLoS One12(8):e0183292.
Link to NCBI Bibliography:https://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/44186401/
I have been very interested in understanding molecular and cellular mechanisms that contribute to skeletal muscle remodeling and diseases. Major research areas include 1) To investigate pathophysiological mechanisms of muscle disorders and to develop treatments; 2) To understand the roles of DUX proteins in mammals; 3) To develop portable sequencing assays as diagnosis and research tools for FSHD and other diseases; 4) To dissect molecular mechanisms and pathways affecting muscle mass and remodeling. A short description of each area is included below.
1) To investigate pathophysiological mechanisms of muscle disorders and to develop treatments: We have been using omics approaches to identify molecular networks and pathways that contribute to different muscle disorders and conditions. Among the diseases studied, we have been most interested in facioscapulohumeral muscular dystrophy (FSHD) which is caused by both genetic and epigenetic mechanisms. After the double homeobox protein 4 (DUX4) was identified as the causative gene of FSHD, we have been studying molecular mechanisms that regulate DUX4 as well as regulated by DUX4. Recently, we shifted research focus to therapeutic development and preparation for clinical trials. In collaboration with Dr. Jean Mah and the Cooperative International Neuromuscular Research Group (CINRG), we conducted a nature history study of early onset FSHD and collected blood samples for biomarker studies using proteomics profiling and RNA-seq. In addition, we are investigating antisense oligonucleotide strategies for knocking down DUX4 in vitro and in vivo as treatments for FSHD.
2) To understand the roles of DUX proteins in animals: Human DUX4 is a retrotransposed gene encoding a double homeobox protein. Expression of DUX4 is restricted to germline cells in healthy individuals. However, it is aberrantly expressed in FSHD muscle cells, which was found to be the cause of the disease. DUX4 is toxic when it is expressed ectopically in frogs, zebra fish, and mice. In addition, it is pro-apoptotic when transiently expressed in mouse myoblasts and human cells. Research efforts have been focused on the pathogenic effects of the DUX4 in muscles. The normal function of DUX4 is not clear. A newly generated conditional transgenic mouse model that carries the DUX4 transgene leaks before transgene induction (from Dr. Peter Jones at University of Nevada). This mild leakiness of DUX4 leads to muscle pathology in the mice. Interestingly, the males also have smaller testes. Human DUX4 is originated from a single DUX gene. Many mammals have paralogues of DUX4 but orthologues exist in primates only. The function of these DUX related genes is not well known. A recent study showed that DUX4 is expressed at the 2-cell-embryo stage during embryogenesis and may play a key role in regulating developmentally regulated genes that are critical to the 2-cell stage (Hendrickson et al, Nat Genet 2017). We are interested in studying the function of DUX proteins and their effects on germline functions and embryogenesis.
3) To develop portable sequencing assays as diagnosis and research tools: Accurate and fast diagnosis of disease conditions is critical for successful disease interventions for both human and animals. MinION sequencer was developed by Oxford Nanopore Technologies and became commercially available in mid-2015. One of the advantages of the MinION sequencer is that it obtains the longest read in comparison to other platforms currently. In our hand, we were able to obtain sequence information of several hundreds Kb in one single read, which allows easier identifications of microorganisms in a specimen as well as genetic mutations associated with rearrangements and repeated sequences. Currently, we have three studies ongoing using the approach.
4) To dissect molecular mechanisms and pathways affecting muscle mass and remodeling: Skeletal muscle is highly plastic and exhibits a wide spectrum of adaptations in response to different environmental and physiological stimuli, including physical activities or different types of exercise, muscle disuse, immobilization, denervation, and microgravity. We have been working with collaborators to dissect molecular pathways involved in muscle remodeling, including pathways involved in exercise induced muscle hypertrophy and endurance; and molecular pathways activated during muscle atrophy and rehabilitation. Among the pathways, we are particularly interested in TGFβ1 pathway, which modulate muscle mass and fibrosis. To investigate the effects of TGFβ1 on skeletal muscle fibrosis and atrophy, we generated a conditional muscle-specific TGFβ1 transgenic mouse model and identified involvement of a novel STAT3 signaling in the pathway. We currently focus at two areas: the cross-talk between TGFβ1 and STAT3 signaling in the muscles; and genetic modifiers that modulate the effects of TGFβ1 in skeletal muscles.
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Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.