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Neuroscience Graduate Program at UCSF

Faculty - David Rowitch, M.D./Ph.D.

Overlapping Mechanisms in CNS Development and Disease


Research Description

My laboratory investigates overlapping mechanisms in CNS development and disease.  We have a long-term interest signaling pathways and transcription factors that regulate gliogenesis, and how insights from development can be applied to glioma, multiple sclerosis (MS) and cerebral palsy (CP). We have shown that the bHLH transcription factor Olig2 required for oligodendrocyte specification and gliomagenesis and that Olig1 is critical for remyelination. We identified the Wnt pathway as a regulator of oligodendrocyte differentiation that might become dysregulated in MS and CP, and the suggesting therapeutic potential of Wnt inhibitors. We have proposed that astrocyte development is organized according to a segmental template regulated by ventral transcriptional factors such as SCL. We performed extensive fate mapping to show restricted origins and allocation of astrocytes throughout the CNS, and now we are interested in regional functions and heterogeneity of astrocytes. I am PI of the first-in-human clinical study of direct neural stem cell transplantation in brain for a myelin disorder. I am committed to training the next generation of investigators, and have mentored physician-scientists, postdoctoral fellows and graduate students in neuroscience; I direct a T32-funded training program for neonatal translational science.

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Current Projects

Oligodendrocyte Lineage Gene Function in the CNS.
This project will test the hypothesis that diverse neurogenic and gliogenic functions of Olig2 are regulated by phosphorylation. We are further defining the role of Olig2 protein expression and post-translational modification in glioma, and specific roles downstream of BRAF and SHH signaling.
                                                                                                                                   
Cellular and Genetic Origins of Astrocytes.
The goal is to identify a set of genetic markers for development of astrocytes and to map their cellular origins in the central nervous system.  The hypothesis to be tested is that astrocytes develop from heterogeneous locations and might have diversified functions in various regions of the CNS.
                         
Pathogenesis and Rational Treatment of Cerebral Palsy.
The goals of this project are to better understand human brain development the nature of neurological damage in premature infants with a view to preventing this devastating complication.
 
BRAF-driven Pediatric Malignant Astrocytoma: Etiology & Treatment
The goal of this project is to identify new information regarding the molecular and cellular etiology of pediatric astrocytomas and new cancer models, as well as related therapeutic observations, for translation to clinical practice.
Role: Co-Investigator

Wnt pathway as a core regulator of oligodendrocyte maturation
Thi sproject is focused on APC gene function in oligodendrocyte development and myelin regeneration

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Lab Members

Grad Students:
Justin Ellis
Kevin Kelley (MSTP)
Vien Nguyen
John Silberis

Technicians:
Mike Wong
Sandra Chang

POSTDOCTORAL FELLOWS AND RESIDENTS:
2013-present
Larry Shiow, MD,PhD
Post-doctoral Fellow, UCSF

2011-present
Hiroko Nobuta, PhD
Post-doctoral Fellow, UCSF

2011-present
Jen Sabo, PhD
Post-doctoral Fellow, UCSF

2006-2013
Steve Fancy, DVM,PhD
Post-doctoral Fellow, UCSF

2010-present
Amelie Griveau, PhD
Post-doctoral Fellow, UCSF

2010-present
Tracy Yuen, PhD
Post-doctoral Fellow, UCSF

2009-present
Anna Molofsky, PhD, MD
Post-doctoral Fellow, UCSF

2009-present
An-Chi Tien, PhD
Post-doctoral Fellow, UCSF

2006-2011
Hui-hsin Tsai, PhD
Research Scientist, HHMI

 

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Selected Publications

  1. Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, Gupta N, Berger MS, Huang E, Garcia-Verdugo JM, Rowitch DH*, Alvarez-Buylla A. Corridors of migrating neurons in the human brain and their decline during infancy. Nature. 2011 Sep 28;478(7369):382-6.
  2. Fancy SPJ, Harrington EP, Yuen T, Silbereis JC, Zhao C, Baranzini SE, Bruce C, Otero JJ, Huang EJ, Nusse R, Franklin RJM and Rowitch DH*. Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination. Nat. Neurosci. 2011 Jun 26;14(8):1009-16.
  3. Huillard E, Hashizume R, Phillips JJ, Griveau A, Ihrie RA, Aoki Y, Nicolaides T, Perry A, Waldman T, McMahon M, Weiss WA, Petritsch C, James CD, Rowitch DH*. Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy. Proc Natl Acad Sci U S A. 2012 May 29;109(22):8710-5.
  4. Heine VM, Griveau A, Chapin C, Ballard PL, Chen JK, Rowitch DH. A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury. Sci Transl Med. 2011 Oct 19;3(105):105ra104. doi: 10.1126/scitranslmed.3002731.
  5. Tsai HH, Li H, Fuentealba LC, Molofsky AV, Taveira-Marques R, Zhuang H, Tenney A, Murnen AT, Fancy SP, Merkle F, Kessaris N, Alvarez-Buylla A, Richardson WD, Rowitch DH*. Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair. Science. 2012 Jun 28.
  6. Gupta N, Henry RG, Strober J, Kang SM, Lim DA, Bucci M, Caverzasi E, Gaetano L, Mandelli ML, Ryan T, Perry R, Farrell J, Jeremy RJ, Ulman M, Huhn SL, Barkovich AJ, Rowitch DH*. Neural stem cell engraftment and myelination in the human brain. Sci Transl Med. 2012 Oct 10;4(155):155ra137. doi: 10.1126/scitranslmed.3004373.

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David Rowitch, M.D./Ph.D.



Email

rowitchd@peds.ucsf.edu

Phone

415-476-7242

Office Address

UCSF Box 0734
533 Parnassus Avenue, room U-503
San Francisco, CA. 94143

Other Websites

Biomedical Sciences Graduate Program

Developmental & Stem Cell Biology Graduate Program

Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research

Helen Diller Family Comprehensive Cancer Center

Neurological Surgery