BBS Faculty Member - Mustafa Sahin

Mustafa Sahin

Department of Neurology

Boston Children's Hospital
Center for Life Science Bldg. 14073
3 Blackfan Circle
Boston, MA 02115
Tel: 617-919-6258
Fax: 617-730-0242
Email: mustafa.sahin@childrens.harvard.edu
Visit my lab page here.



The research in the Sahin lab is directed at understanding the cellular mechanism(s) of axon guidance and its relationship to neurological dysfunction. There are two major lines of ongoing research in the lab. First is the role of tuberous sclerosis genes in axons. Tuberous sclerosis (TSC) is a multi-system autosomal dominant disease, which is characterized by the formation of benign tumors (hamartomas) in several organs. The brain is almost invariable affected, and patients can present with epilepsy, autism and intellectual disability. However, a key, unresolved issue is what causes the neurological symptoms in TSC patients. Dr. Sahin's lab hypothesized that the miswiring of connections between neurons contributes to the pathogenesis of autism and epilepsy in TSC. They have generated several lines of evidence to show that TSC proteins play crucial roles in neuronal polarity, axon guidance, and myelination. Most recently, they have demonstrated a crucial role for TSC proteins in cerebellar Purkinje cells, mediating autistic-like behavior in mice.

The second major line of ongoing research is the role of axonopathy in spinal muscular atrophy (SMA). SMA is an autosomal recessive disease characterized by hypotonia and muscle weakness due to loss of the spinal motor neurons. Molecular genetic studies has revealed that mutations in Smn1 gene are responsible for this disease, and the SMN protein is involved in RNA processing. Despite these advances, little is known regarding the exact role of SMN in nervous system function and the nature of the RNA processing defects that underlie SMA pathology have remained elusive. It is known that SMN protein is localized to the axon and the growth cone. Furthermore, in the absence of full-length SMN, the axons are shorter, and the growth cones are smaller. Taken together, these findings suggest that dysregulation of RNA transport or translation may underlie SMA pathology. Therefore, the Sahin lab is working on identifying the protein partners and RNA cargoes of the SMN complex in axons. We recently identified two binding partners of SMN in axons: HuD protein and cpg15/neuritin mRNA.

To study axon development, the lab utilizes a variety of in vivo and in vitro assays and molecular and biochemical techniques. They use neurons in dissociated neuronal cultures, and they take advantage of mouse models of neurological disease. In addition, they are performing analyses to quantitatively measure the relative abundance of proteins and RNA in isolated fractions and complexes. Employing these varied techniques, Dr. Sahin is examining the molecular regulation of axon development and the functional consequences for neurologic disease.



Last Update: 6/4/2014



Publications

For a complete listing of publications click here.

 


 

Choi Y-J, Di Nardo A, Kramvis I, Meikle L, Kwiatkowski DJ, Sahin M*, He X*. Tuberous sclerosis complex proteins control axon formation. Genes Dev 2008;22:2485-95 (*co-corresponding authors).

Nie D, Di Nardo A, Han JM, Baharanyi H, Kramvis I, Huynh T, Dabora S, Codeluppi S, Pandolfi PP, Pasquale EB,
Sahin M. TSC2-Rheb signaling regulates EphA-mediated axon guidance. Nat Neurosci 2010;13:163–172. PMC2812631.

Akten B, Kye MJ, Hao LT, Wertz MH, Singh S, Nie D, Huang J, Merianda TT, Twiss JL, Beattie CE, Steen J,
Sahin M. Interaction of SMN and HuD with cpg15 mRNA rescues motor neuron axonal deficits. Proc Natl Acad Sci U S A. 2011;108(25):10337-42.

Tsai PT, Hull C, Chu YX, Greene-Colozzi E, Sadowski A, Leech JM, Steinberg J, Crawley JN, Regehr WG,
Sahin M. Autistic-like behavior and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature, 2012 Jul 1. doi: 10.1038/nature11310.



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