Cell Biology, Neurobiology & Anatomy

Jered McGivern, PhD

Research Area:  Developing novel culture systems using patient derived induced pluripotent stem cells to model neurodegenerative disease

The complex genetic components that cause Spinal Muscular Atrophy (SMA) are only found naturally in humans. Therefore it is advantageous to study this disease using cells taken from patients with SMA that have been reverted to an embryonic-like state (induced pluripotent stem cells - iPSCs). From these cells we can form many of the tissues of the human body including motor neurons and skeletal muscle. Defects in neuromuscular junction stability are seen in animal models of SMA and these defects may play a role in motor neuron loss and muscle atrophy. This has yet to be evaluated in a human system; therefore, I am examining neuromuscular junctions in human muscle and motor neuron cultures to provide insight into disease progression. The goal is to generate an enriched population of skeletal muscle from iPSC lines derived from patients with SMA. Developing this method will allow us to examine motor neurons in the context of their natural synaptic targets, skeletal muscle, and determine the influence of post and pre-synaptic influences on the disease progression of SMA. Furthermore, the development of this system will be very useful in modeling other neurodegenerative diseases, for example ALS, where a majority of patients have a sporadic form of the disease and therefore difficult to model using rodent systems.

Education and Training:

2011-present - Postdoctoral Fellow. Medical College of Wisconsin, Milwaukee (Supervised by Dr. Allison Ebert)

2004-2010 - Postdoctoral Fellow. University of Wisconsin-Madison, Madison (Supervised by Dr. Clive Svendsen)

2002-2008 PhD-Biomolecular Chemistry. University of Wisconsin-Madison (Supervised by Dr. Michael D. Sheets)

1998-2002 BA - Chemistry. St. Olaf College, Northfield, MN

Publications:

• Toward defining the dynamic phosphoproteome of Xenopus laevis embryos. McGivern JV, Swaney DL, Coon JJ, and Sheets MD. Dev Dyn. 2009. Apr 21.
• Structural basis for RNA recognition by a type II poly(A) binding protein. Song J*, McGivern JV*, Nichols KW, Markley JL, and Sheets MD Proc Natl Acad Sci USA. 2008. Oct 7; 105(40):15317-22. *Co-first authors. Faculty of 1000 Biology: evaluations for Song J et al Proc Natl Acad Sci U S A 2008. Sep 29.
• Spatially restricted translation of the xCR1 mRNA in Xenopus embryos. Zhang Y, Forinash KD, McGivern J, Fritz B, Dorey K, Hill C, Sheets MD. Mol Cell Biol. 2009. Apr 13.