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Neuroscience Graduate Program at UCSF
Overlapping Mechanisms in CNS Development and Disease
New insight into human neurological disease has emerged from investigation of normal pathways of brain development. The Rowitch laboratory investigates Sonic hedgehog (Shh) signaling in regulation of neural stem cell proliferation and specification. We have shown that Shh is a potent mitogen for neuronal precursors and the pediatric brain cancer, medulloblastoma. Additionally, we have demonstrated that Olig genes are essential for specification of oligodendrocytes and motor neurons. We are investigating roles for Olig genes in CNS tumorigenesis, multiple sclerosis and newborn neurological injury. Recently shown that the bHLH protein SCL is a regulator of astrocyte specification through cross-antagonistic interactions with Olig2.
The Rowitch Laboratory’s general interest is in overlapping mechanisms in brain development and neurological diseases such as multiple sclerosis, cancer and newborn brain injury. It has focused, in particular, on the regulatory role of transcription factors. In addition to laboratory research, Dr. Rowitch attends in the Intensive Care Nursery in the Children's Hospital at UCSF Medical Center.
Oligodendrocyte Lineage Gene Function in the CNS. The major goals of this project are to define cis- and trans-acting regulatory elements that govern Olig2 expression in the embryonic spinal cord; to test the hypothesis that diverse neurogenic and gliogenic functions of Olig2 are regulated by phosphorylation; to define the role of Olig expression in glioma.
Genetics and Biology of Malignant Glioma. The major goals of this Project are to determine roles for EGFR signaling in survival, proliferation, and differentiation along the NSC-to-astrocyte axis; to determine the impact of glioma-relevant tumor suppressor deficiency on EGFR-mediated survival and differentiation along the NSC-astrocyte axis; to use genetic profiling information to identify transcription factors with functional roles during astrocyte lineage development in the mammalian CNS; to functionally screen genes identified in for factors involved in glioma progression.
Manipulation of Olig Gene Function in Multiple Sclerosis and Transcriptional Control of Effective Re-myelination. The broad goal of this Project is to develop methods to manipulate the genes and signaling pathways that direct endogenous oligodendrocyte progenitor cells to proliferate, differentiate and remyelinate within the damaged human brain.
Molecular Mechanisms of Fate Choice in Neural Stem Cells. The objective of this Project is to define the molecular mechanisms that regulate fate choice and subtype specification in the developing vertebrate central nervous system. A particular emphasis is on the identification of pathways that regulate formation of oligodendrocytes and astrocytes.
Cell Cycle Regulation During CNS Development by Hedgehog Signaling and Proto-oncogene in N-myc. The major goals of this project are to define precise mechanisms underlying proliferative effects of Hedgehog signaling during CNS development and tumorgenesis.
Grad Students and Lab Techs:
Emily Harrington
John Silbereis
Vien Nguyen
Khalida Sabeur
POSTDOCTORAL FELLOWS AND RESIDENTS:
2006-present
Steve Fancy, DVM/Ph.D.
Post-doctoral Fellow, UCSF
2010-present
Amelie Griveau, Ph.D.
Post-doctoral Fellow, UCSF
2009-present
Anna Molofsky, Ph.D., M.D.
Post-doctoral Fellow, UCSF
2009-present
Jose Otero, Ph.D., M.D.
Post-doctoral Fellow, UCSF
2008-present
Greg Potter, Ph.D
Post-doctoral Fellow, UCSF
2009-present
An-Chi Tien, Ph.D.
Post-doctoral Fellow, UCSF
10/06-present
Hui-hsin Tsai, PhD
Post-doctoral Fellow, UCSF
2010-present
Tracy Yuen, PhD
Post-doctoral Fellow, UCSF
- Kenney AM, Rowitch DH*. Sonic hedgehog promotes G1 cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. MCB, 2000; 20, 9055-9067. Times cited: 245
- J Chan, AP McMahon, CD Stiles, DH Rowitch*. Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron, 2000 Feb;25(2):317-29. Times cited: 429
- Lu QR, Sun T, Zhu Z, Ma N, Garcia M, Stiles CD, Rowitch DH*. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte lineage connection. Cell, 2002; 109, 75-86. Times cited: 381
- Muroyama Y, Fujiwara Y, Orkin SH, Rowitch DH*. Specification of astrocytes by bHLH protein SCL in a restricted region of the neural tube. Nature 2005; 438:360-3. Times cited: 52
- Ligon KL, Huillard E, Mehta S, KesariS, Liu H, Alberta J, Bachoo RM, Kane M, Louis DN, DePinho RA, Anderson DJ, Stiles CD, Rowitch DH*. Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. Neuron. 2007; 53:503-17. (PMCID: 1810344). Times cited: 92
- Schüller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, Huillard E, Sun T, Ligon AH, Qian Y, Ma Q, Alvarez-Buylla A, McMahon AP, Rowitch DH*, Ligon KL. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell. 2008 Aug 12;14(2):123-34. (PMCID: 2597270). Times cited: 75
- Fancy SP, Baranzini SE, Zhao C, Yuk DI, Irvine KA, Kaing S, Sanai N, Franklin RJ, Rowitch DH*. Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev. 2009 Jun 10. (PMCID: 2704469). Times cited: 48
- Heine VM, Rowitch DH*. Hedgehog signaling has a protective effect in glucocorticoid-induced mouse neonatal brain injury through an 11betaHSD2-dependent mechanism. J Clin Invest. 2009 Feb;119(2):267-77. (PMCID: 2631296). Times cited: 13
- 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. Times cited: 1
- Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai H-H, Wong M, Gupta N, Berger MS, Huang E, Garcia-Verdugo J-M, Rowitch DH* and Alvarez-Buylla A. Corridors of Migrating Neurons in Human Brain and Their Depletion During Infancy. Nature. 2011 Sept 28 [Epub ahead of print].
- Heine VM, Griveau A, Chapin C, Ballard PL, Chen JK, Rowitch DH. A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury. Science Translational Medicine. 19 October 2011: 105ra104.
*Indicates Rowitch as corresponding or co-corresponding author.
David Rowitch, M.D./Ph.D.
Phone
415-476-7242
Physical Address
Parnassus
UC Hall U503
Box 0734
Mailing Address
533 Parnassus Ave, Box 0734
University of California, San Francisco
San Francisco, CA. 94143 - 0734
Other Websites
Biomedical Sciences Graduate Program
Developmental & Stem Cell Biology Graduate Program
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research