Cell and Gene Therapy Fellowship Program

Major Clinical and Investigative Interests

The goal of our Center is to develop 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 (Division of Cell & Gene Therapy): Focus on stem cell biology for disease modeling and cell replacement

• Glial progenitor-based cell therapy in myelin disease: pediatric leukodystrophies and multiple sclerosis
• Tumor stem cells and gliomas of the adult CNS
• Inducing neuronal replacement from endogenous progenitors in Huntington’s disease
• Use of human iPSC and hESC-derived neural progenitors for disease modeling
• Transcriptional and pathway regulation of progenitor cell types of the adult human CNS
• Stem cell-modeling of glial involvement in neuropsychiatric and neurodegenerative disorders

Nedergaard Lab (Division of Glial Therapeutics): Focus on glial physiology and pathophysiology

• Mechanisms of CSF clearance and fluid homeostasis in both normal and injured CNS
• The role of astrocytes in modulating the awake state and consciousness
• 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

Structure

Besides current faculty, the unit includes over 50 postdoctoral fellows, technicians, administrative staff, and graduate students, and hosts another 20 undergraduates. The labs are highly collaborative, with many investigators pursuing projects between the principal lab groups. The group’s work is currently supported by NIH R01 grants (10), NIH R21 grants (1), Program Project grants (1), the New York State Stem Cell Program (2 grants), and a variety of foundations that include the National MS Society, the National Science Fdn, the CHDI Fdn, the Adelson Medical Research Fdn, the Crask Fdn, the Mathers Fdn, Leducq Fdn, PML Consortium, and individual pre- and postdoctoral training grants from the AHA and Lundbeck Foundations.

Total current funding exceeds $25 million, or roughly $5 million/year, and has increased most years since formation of the Center. Past and present biotech and pharmaceutical collaborators include Biogen Idec, Sanofi, and Merck, advancing the translational scope of these studies.

Drs. Goldman and Nedergaard have recently expanded the Center’s reach to include a new Center for Basic and Translational Neuroscience at the University of Copenhagen, which opens in July 2015 with funding by the Novo Nordisk Foundation. This new Center should facilitate involvement of faculty and fellows alike in European as well as American multi-institutional research projects.

Track record

The Center has enjoyed consistent productivity, and is one of the most well-recognized in American neuroscience; Goldman and/or Nedergaard have each published >200 papers, over 50 together. The Center’s papers over the last few years have appeared in Science, Science Translational Medicine, Science Signaling, Cell, Cancer Cell, Cell Stem Cell, Nature Medicine, Nature Biotechnology, Nature Neuroscience, Nature Communications, Proceedings of the National Academy of Sciences, the Journal of Neuroscience, Neuroscience, Neurotherapeutics, both the Archives and Annals of Neurology, Neuron Glia Biology, Glia, and others.

Contact

Steven Goldman, M.D., Ph.D.
Maiken Nedergaard, M.D., DMSc.

Phone: (585) 275-9550 (Dr. Goldman)
(585) 273-2868 (Dr. Nedergaard)
Fax:(585) 276-2298
steven_goldman@urmc.rochester.edu
nedergaard@urmc.rochester.edu