- Johns Hopkins University School of Medicine
- Location: Baltimore, MD
- Job Number: 7087389
- Posting Date: Oct 19, 2021
- Application Deadline: Open Until Filled
Job DescriptionWe are looking for highly motivated postdoctoral candidates to join the laboratory of Charlotte Sumner, MD at Johns Hopkins University to lead studies elucidating mechanisms of neurodegenerative disorders of motor neurons. The long-term goal of our research program is to advance therapeutics for spinal muscular atrophies (SMAs), early-onset motor neuron (MN) diseases causing early mortality. We focus on proximal SMA caused by recessive mutations of the survival motor neuron 1 gene (SMN1) and distal SMA (dSMA) caused by dominant mutations of the transient receptor potential vanilloid 4 gene (TRPV4) because of fundamental roles played by the encoded proteins in the nervous system and their therapeutic tractability.In recent studies of proximal SMA, we have demonstrated that pathology begins in utero, before treatments are currently initiated in patients.
Current projects: 1) dissect mechanisms regulating SMN expression during development and treatment, 2) identify mechanisms causing impaired maturation and degeneration of SMA MNs, and 3) develop novel and in utero SMA therapeutic strategies. In recent studies on dSMA, we have shown that mutations of TRPV4 disrupt regulatory protein-protein interactions, cause a gain of channel function, and breakdown of blood neural barriers. Current projects: 1) characterize protein interactions regulating TRPV4 channel activity, 2) evaluate the role of TRPV4 in modulating EC barrier function, and 3) assess TRPV4 antagonists as a therapeutic strategy in dSMA mice and ultimately other disorders characterized by BNB disruption. Experimental approaches include human genetics, biochemistry, cell biology, molecular imaging of human material and mouse models (including 7 new genetically engineered mouse lines in the past 5 years). Additional new experimental approaches include iDISCO, isogenic iPSC-derived 3D culture systems, and spatial and single-cell transcriptomics.