New Approaches for Treating Neurological Diseases
The Center for Translational Neuromedicine focuses on the development of new approaches for treating neurological diseases, primarily using cell and gene therapy. Our emphasis is on using these technologies to mobilize endogenous stem and progenitor cells of the adult brain and spinal cord, as a means of structural repair. In addition, stem cell isolation and genomics analysis, as well as advanced imaging and transplant strategies are also pursued, both for biological assessment and therapeutic modeling. Our disease targets are those attributable to dysfunction or loss of single cell types; for instance, demyelinating disease is studied as a potential target for oligodendrocyte progenitor cell delivery, while Huntington’s Disease is studied as a potential beneficiary of medium spiny neuronal replacement from endogenous stem cells. Conversely, gliomas and gliomagenesis are studied from the standpoint of dysregulated signaling by endogenous glial progenitors. The principal groups in the Center include Dr. Goldman’s, whose division focuses on neural stem and glial progenitor biology, and Dr. Nedergaard’s, whose division focuses on astrocytic physiology and pathology, as well as on cerebral blood flow and its glial regulation.
Goldman Lab (Division of Cell & Gene Therapy)
Focus on cell replacement, tumorigenesis, and myelin disease
- Glial progenitor-based cell therapy in myelin disease: pediatric leukodystrophies and multiple sclerosis
- Tumor stem cells and gliomas of the adult CNS
- Inducing endogenous progenitors as a means of treatment in Huntington’s disease
- Use of human iPSC and ES cell-derived neural progenitors for drug development and disease modeling
- Transcriptional and pathway regulation of progenitor cell types of both the fetal and adult human CNS
Nedergaard Lab (Division of Glial Therapeutics)
Focus on stroke and traumatic brain and spinal cord injury
- Mechanisms of CSF clearance and fluid homeostasis in both normal and injured CNS
- The role of astrocytes in epileptogenesis and the treatment of seizure disorders, especially post-stroke
- Therapeutic targeting of neuronal-astrocytic interactions in stroke and traumatic brain injury
- Targeted modulation of reactive gliosis in stroke
- Developing new modalities for imaging native and transplanted glial progenitors in vivo
- Glial targeted treatment of both acute spinal cord injury and spinal neurodegenerative disease
Cell and Gene Therapy
Wang S; Bates J; Li X; Schanz S; Chandler-Militello D; Levine C; Maherali N; Studer L; Hochedlinger K; Windrem M; Goldman SA. "Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination." Cell stem cell. 2013; 12(2):252-64.
Han X; Chen M; Wang F; Windrem M; Wang S; Shanz S; Xu Q; Oberheim NA; Bekar L; Betstadt S; Silva AJ; Takano T; Goldman SA; Nedergaard M. "Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice." Cell stem cell. 2013; 12(3):342-53.
Glial Disease & Therapeutics
Sun W; McConnell E; Pare JF; Xu Q; Chen M; Peng W; Lovatt D; Han X; Smith Y; Nedergaard M. "Glutamate-dependent neuroglial calcium signaling differs between young and adult brain." Science (New York, N.Y.). 2013; 339(6116):197-200.
Iliff JJ; Nedergaard M. "A link between glial Ca2+ signaling and hypoxia in aging?" Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2013; 33(2):170. Epub 2012 Dec 05.