Medical College of Wisconsin
Department of Cell Biology, Neurobiology & Anatomy
8701 Watertown Plank Road
Milwaukee, WI 53226-3548
(414) 955-6517 (fax)
PhD, Northwestern University, Chicago, IL, 2005
BS, Indiana University, Bloomington, IN 1999
Therapeutic uses of stem cells and disease modeling for spinal muscular atrophy, amyotrophic lateral sclerosis, Parkinson’s disease, and muscular dystrophy
neurons differentiated from human embryonic stem cells
My research interests are in the area of neurodegenerative diseases, both understanding the molecular basis for the disease progression and finding effective experimental therapies. My current research focuses on using induced pluripotent stem cells (iPSCs) derived from patient tissue to understand disease mechanisms and therapeutic intervention. One project in my lab is investigating the cell death processes involved in motor neuron loss in spinal muscular atrophy (SMA). We are using iPSCs derived from SMA patients to generate motor neurons and astrocytes to determine how the motor neurons are. My lab has found that astrocytes are dysfunctional in SMA, so we are investigating the mechanisms by which they contribute to disease pathology including alterations in secreted proteins and microRNAs. My lab also uses gene therapy and cell transplantation as potential therapeutic strategies for SMA. The second project is investigating the mechanisms underlying motor neuron loss in amyotrophic lateral sclerosis (ALS). We are using patient-specific iPSCs to assess protein aggregation in common and rare genetic forms of ALS. We incorporate gene editing techniques to create specific iPSCs for differentiation into motor neurons, astrocytes, and skeletal muscle. The third project is evaluating the effect of the G2019S LRRK2 mutation on mitochondrial trafficking and cytoskeletal structure in iPSC-derived dopamine neurons and sensory neurons. We have found the same mutation induces different consequences depending on the cell type being examined, so we are now using live cell imaging to determine mitochondrial and vesicular motility in an effort to correlate neuron-specific defects to disease phenotypes. Finally, we are examining the secretome and microRNA profile of dystrophin deficient iPSC-derived myocytes to identify novel therapeutic targets to treat muscular dystrophy.
Jered McGivern, PhD, Postdoctoral Fellow, January 2011-July 2014, is now an Assistant Professor in the Department of Biochemistry at Lakeland College, Sheboygan, WI.