Current Laboratory Projects    

 

 
 

SPTBN2: Diagnostic Marker

Prior work from our laboratory has demonstrated that β-III-spectrin is highly expressed in MPNSTs, but not plexiform neurofibromas suggesting that β-III-spectrin could play an important role in the progression and diagnostics of these tumors. Knockdown of β-III-spectrin significantly increased cell death in vitro and in vivo in a subcutaneous tumor model.  Additionally, in the metastasis model, knockdown of β-III-spectrin led to a decreased tumor burden and increased overall survival.  Knockdown of β-III-spectrin was also associated with mis-localization of the mGluR1 glutamate receptor, a G-protein coupled receptor that can affect cell survival.   Additionally, β-III-spectrin –deficient cells had decreased levels of EAAT4, a glutamate transporter.

Recent findings in the lab have made us very excited about this target. More work is needed to understand what is happening to cause this difference and whether that pathway can be targeted therapeutically. Stay tuned!

Recent findings in the lab have made us very excited about this target. More work is needed to understand what is happening to cause this difference and whether that pathway can be targeted therapeutically. Stay tuned!

Using RNA sequencing from the original patient and the xenograft we are exploring similarities and differences. 

Using RNA sequencing from the original patient and the xenograft we are exploring similarities and differences. 

 

ATRX: Prognostic Marker

Previous work in our lab had identified ATRX chromatin remodeler (ATRX), previously termed, Alpha Thalassemia/Mental Retardation Syndrome X Linked, as a gene mutated in a subset of MPNSTs. Given the great need for novel biomarkers and therapeutic targets for MPNSTs, we sought to determine the expression of ATRX in a larger subset of sporadic and NF1 associated MPNSTs (NF1-MPNSTs). We performed immunohistochemistry (IHC) on MPNSTs (NF1-associated and sporadic), plexiform neurofibromas, and atypical neurofibromas. We demonstrated that ATRX is aberrantly expressed in the majority of NF1-MPNSTs, but not plexiform or atypical neurofibromas. Additionally, aberrant ATRX expression is associated with decreased overall survival in NF1-MPNST, but not sporadic MPNST and may serve as a prognostic marker for patients with NF1-MPNST.