Cell and Gene Therapy

Center For Translational Neuromedicine
Division of Cell and Gene Therapy / Division of Glial Diseases and Therapeutics

Faculty

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 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

Structure and track record: Besides 18 current faculty, the unit includes over 35 postdoctoral fellows, technicians 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 7 NIH R01 grants, a DOD multi-investigator grant, an R25 training grant, the New York State Stem Cell Program (3 grants), and a variety of foundations that include the National MS Society (3 grants), the CHDI Foundation (6 FTEs), the Adelson Medical Research Foundation (4 grants), the Crask foundation, the Mathers Foundation, several young investigator awards, and individual pre- and postdoctoral training grants from both NIH and the AHA. Total current funding exceeds $20 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 Aventis, Regeneron, and Merck, advancing the translational scope of these studies. 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, and together have averaged a first-line paper (IF>20) every 6 months for the past 15 years. 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, 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 Person:	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
Email:	steven_goldman@urmc.rochester.edu nedergaard@urmc.rochester.edu