The ASPIRE Path in Molecular Medicine

The overarching goal of my thesis project is to characterize the biological mechanisms by which mutations in the ELFN1 gene cause ADHD and epilepsy in humans and discover small molecule drugs that have the potential to treat these disorders by targeting these mechanisms. ELFN1 encodes for extracellular leucine rich repeat and fibronectin type III domain containing 1 (Elfn1), which is a postsynaptic scaffolding protein that anchors metabotropic glutamate receptor 7 (mGlu7) into place on presynaptic neurons. Because mutations in the genes encoding for mGlu7 (GRM7) and ELFN1 are associated with ADHD and epilepsy, designing a drug that selectively targets this mGlu7-Elfn1 complex may provide an alternative treatment option with reduced side effects for patients. The plan for this project is two-fold: one, identify how these mutations cause psychological changes in neural networks associated with ADHD and epilepsy using electrophysiology and other techniques to assess behavior and perturb neural activity in vivo. And two, attempt to characterize small molecule drugs that selectively bind to this Elfn1-mGlu7 synaptic complex using various in vitro molecular pharmacology techniques, and eventually translate these findings to in vivo models.