Alexander Neuromuscular Disease Research Lab

Twitter background muscle pic v2Non-coding RNAs as modifiers of neuromuscular disease- The Alexander lab is especially interested in determining the functional roles of non-coding RNAs (microRNA, lncRNAs, and snRNAs) in both normal and diseased muscle.  We identified one particular microRNA, miR-486, as a muscle-enriched miRNA that is strongly reduced in expression levels in Duchenne muscular dystrophy (DMD), but not the milder Becker muscular dystrophy (BMD).  Additionally, we demonstrated that miR-486 overexpression in dystrophic mouse muscles can block the progression of DMD symptoms and improve overall muscle performance and physiology (Alexander et al., JCI, 2014).  We are now characterizing the targets of miR-486 in skeletal muscle, in addition to determining if miR-486 expression levels can be used as a biomarker for disease progression in DMD and other muscular dystrophies.

MyoD1eGFP pos picA 002Epigenetic regulation of normal and diseased muscle-
We are also very interested in uncovering novel epigenetic regulators of normal and diseased skeletal muscle.  We seek to answer the questions such as how can two genetically-related brothers with the exact same pathogenic disease mutation have two dramatically different clinical phenotypes?  Our past work uncovered the JAG1 genomic locus as a modifier of DMD (Vieira et al., Cell, 2015).  We are actively seeking to identify additional loci that modify the disease pathology and/or progression in DMD and other muscular dystrophies.  We are currently characterizing several histone modifier and RNA-splicing proteins that may affect muscle formation and maintenance in our vertebrate animal models.

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Generation, characterization, and therapeutic drug screening of novel zebrafish models of human neuromuscular diseases-  The lab uses the zebrafish model as a powerful tool for both genetic discovery and functional analysis of factors that regulate muscle development and disease.  We use the latest transgenic (Tol2 and inducible) and gene editing (CRISPRs) techniques to manipulate the zebrafish genome to discover novel pathways and mechanisms for normal and disease muscle regulation.  We then use these novel zebrafish neuromuscular disease models to perform both targeted (known compound) and unbiased (drug compound library) screens to identify novel corrective drug compounds for the treatment of muscle diseases.  Our lab has identified and defined a set of reproducible criteria for evaluating the therapeutic efficacy of lead compounds in various zebrafish muscle mutant models.
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Giving back to the patient and local communities –
 A major focus of the lab is to give back to the neuromuscular disease patient community.  To fulfill this obligation we take part in giving back by participating in various fundraisers, awareness events, and community outreach events.  We also fulfill our obligation of service to the local Birmingham community by speaking with various students about our science and offering up summer internships in the lab.  Additionally, members of the Alexander lab take part in the local MDA walks and host patients whom are interested to learn more about the muscle research that takes place in the lab.