Yiumo Michael Chan, PhD
Senior Scientist, Protein Therapeutics Group
McColl-Lockwood Laboratory for Muscular Dystrophy Research
Department of Neurology
Prior Positions and Experience
||Staff Scientist, Weis Center for Research, Geisinger Clinic
||Postdoctoral Fellow, Boston Children’s Hospital, Harvard Medical School
PhD: 1995, University of Chicago
BS: 1989, University of Chicago
Molecular Mechanisms of Muscular Dystrophies
Dr. Chan’s main research focus is on limb-girdle muscular dystrophies (LGMD), a group of progressive muscle wasting diseases characterized by primary involvement in pelvic and shoulder girdle muscles. In particular, we are interested in understanding the role of fukutin-related protein (FKRP) in LGMD2I and other muscular dystrophies. Patients carrying mutations in the FKRP gene may also develop dilated cardiomyopathy and abnormalities in the central nervous system. Our long-term goal in the laboratory is to elucidate the molecular mechanisms underlying FKRP-related muscular dystrophies and to develop treatments for the disease.
The function of FKRP is not well understood. The single-pass transmembrane protein is thought to encode a putative glycosyltransferase enzyme involved in post-translational modification of a-dystroglycan, a crucial component of the dystrophin-glycoprotein complex (DGC) at the sarcolemma. Alpha-dystroglycan binds to laminin in the extracellular matrix and is critical for maintaining the stability of the muscle membrane. Recent studies have provided evidence that abnormal glycosylation of a-dystroglycan plays an important but, as yet undefined role in the pathogenesis of muscular dystrophies. Supporting this idea, mutations in several genes encoding glycosyltransferases known to modify a-dystroglycan have been reported to cause different forms of muscular dystrophies.
Dr. Chan is currently using both knockin and knockout animal models to investigate the function of FKRP and its role in -dystroglycan modifications. In addition, Dr. Chan is pursuing protein therapeutics as potential treatment for LGMD2I. The strategy aims to deliver an exogenous source of proteins to the targeted tissues to improve functions. Other areas of his research include identification of novel protein-protein interactions in muscular dystrophies by chemical cross-linking and proteomics. Dr. Chan is also investigating the cellular mechanisms by which sarcoglycans contribute to the stability of myelin sheath in peripheral neuropathy.
Chan YM, Keramaris-Vrantsis E, Lidov HG, Norton JH, Zinchenko N, Gruber HE, Thresher R, Blake DJ, Ashar J, Rosenfeld J, LuQL. Fukutin-related protein is essential for mouse muscle brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies. Human Molecular Genetics 2010, in press. [PMID: 20675713]
Lu PJ, Zillmer A, Wu X-H, Vachris J, Blake DJ, Lochmuller H, Chan YM, Lu QL. Mutations alter secretion of fukutin-related protein. Biochim Biophys Acta - Molecular Basis of Disease 2010; 1802:253-258. [PMID: 19900540]
Chan YM, Brown SC, Lu QL. International Workshop: Glycosylation Defects in Muscular Dystrophies - Enhancing glycosylation to fight muscle diseases, 15-16 May, 2008, Charlotte, USA. Neuromuscular Disorders 2008; 18: 1002-1004[PMID: 18974003]
Stecker MM, Baylor KA, Chan YM. Acute nerve compression and the compound motor action potential. J Brachial Plex Peripher Nerve Inj 2008; 3:1. [PMID: 18211681]
Cai H, Erdman RA, Zweier L, Chen J, Baylor KA, Shaw JH, Stecker MM, Carey DJ, Chan YM. The sarcoglycan complex in Schwann cells and its role in myelin stability. Exp Neurol2007; 205: 257-269. [PMID: 17397833]
Chen, J , Shi W, Zhang Y, Sokol R, Cai H, Lun M, Moore BF, Farber MJ, Stepanchick JS, Bonnemann CG, Chan YM. Identification of functional domains in sarcoglycans essential for their interaction and plasma membrane targeting. Exp Cell Res 2006; 312: 1610-1625. [PMID: 16524571]
Current, Recent and Pending Grant Support
Grant Title: The Assembly of the Sarcoglycans and Their Role in Muscular Dystrophies
Funding Agency: Muscular Dystrophy Association
Role: Principal Investigator
Years: 2004 – 2006