David H. Rowitch MD, PhD
Professor of Pediatrics and Neurological Surgery
Chief of Neonatology
Howard Hughes Medical Institute Investigator
Central Nervous System Development and Tumorigenesis. New insight into human neurological diseases has emerged from investigation of normal pathways of brain development. Dr. Rowitch's laboratory investigates Sonic hedgehog (Shh) signaling in regulation of neural stem cell proliferation and specification and the critical roles played by downstream transcription factors. During postnatal brain development, Sonic hedgehog (Shh) functions as potent mitogen for cerebellar granule neuron precursors (CGNP). Dr. Rowitch's research has established that N-myc and D-type cyclins are amongst the common targets of Shh signaling in CGNP and medulloblastoma, and he has used global measures of gene expression to further validate the relationship between brain development and tumorigenesis. In the embryonic neural tube, Shh is essential for development of oligodendrocytes. The work of Dr. Rowitch and colleagues has also shown that activation of Olig genes is a critical component of oligodendrocyte specification from neural stem cells. Interestingly, Olig genes show ongoing expression in glioma and multiple sclerosis and preliminary evidence suggests diverse functions for Olig proteins in such lesions.
Education, Training, and Previous Positions
- 1982: BA, University of California, San Diego
1988: PhD, University of Cambridge, U.K.
1989: MD, University of California, Los Angeles School of Medicine
1989: Internship and Residency, Department of Pediatrics, Children's Hospital, Boston, MA
1992: Fellowship in Newborn Medicine, Children's Hospital, Boston, MA
1994: Postdoctoral Fellow, Harvard College, Cambridge, MA
1996: Instructor in Pediatrics, Harvard Medical School
1999: Assistant Professor of Pediatrics, Harvard Medical School
2004: Associate Professor of Pediatrics, Harvard Medical School
Selected Professional Memberships and Appointments
- Howard Hughes Medical Institute Investigator
Society for Pediatric Research
Society of Neuroscience
American Pediatric Society
Cambridge Philisophical Society
Selected Honors and Awards
- 2008: Investigator, Howard Hughes Medical Institute
2002-2007: James S. McDonnell Foundation Research Award
2000-2005: Weaver Neuroscience Scholar, National Multiple Sclerosis Society
2000-2002: Kimmel Scholar, Sidney Kimmel Foundation for Cancer Research
1998-2000: Basil O'Connor Starter Scholar Award, March of Dimes Foundation
1997-2002: NIH Clinical Investigator Award
1993-1996: Postdoctoral Fellowship for Physicians, Howard Hughes Medical Institute
1987-1989: Mandel Scholarship, UCLA School of Medicine
1987-1989: Medical Scientist Training Program, UCLA School of Medicine
1985-1987: Overseas Research Student Award, Council of Vice Chancellors and Principals, U.K.
1985-1987: Oliver Gaty Studentship in Biophysics, University of Cambridge, U.K.
Selected Recent Publications
Billiards SS, Haynes RL, Folkerth RD, Borenstein NS, Trachtenberg FL, Rowitch DH, Ligon KL, Volpe JJ, Kinney HC. Myelin Abnormalities without Oligodendrocyte Loss in Periventricular Leukomalacia. Brain Pathol 2008; [Epub ahead of print].
Schüller U, Zhao Q, Godinho SA, Heine VM, Medema RH, Pellman D, Rowitch DH. Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors. Mol Cell Biol 2007;27(23):8259-70.
Petryniak MA, Potter GB, Rowitch DH, Rubenstein JL. Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron 2007;55(3):417-33.
Ligon KL, Huillard E, Mehta S, Kesari S, Liu H, Alberta JA, 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(4):503-17.
Rousseau A, Nutt CL, Betensky RA, Iafrate AJ, Han M, Ligon KL, Rowitch DH, Louis DN. Expression of oligodendroglial and astrocytic lineage markers in diffuse gliomas: use of YKL-40, ApoE, ASCL1, and NKX2-2. J Neuropathol Exp Neurol 2006;65(12):1149-56.
Hatton BA, Knoepfler PS, Kenney AM, Rowitch DH, de Alborán IM, Olson JM, Eisenman RN. N-myc is an essential downstream effector of Shh signaling during both normal and neoplastic cerebellar growth. Cancer Res 2006;66(17):8655-61.
Ligon KL, Kesari S, Kitada M, Sun T, Arnett HA, Alberta JA, Anderson DJ, Stiles CD, Rowitch DH. Development of NG2 neural progenitor cells requires Olig gene function. Proc Natl Acad Sci U S A 2006;103(20):7853-8.
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(7066):360-3.
Sjostrom SK, Finn G, Hahn WC, Rowitch DH, Kenney AM. The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors. Dev Cell 2005;9(3):327-38.
Ligon KL, Alberta JA, Kho AT, Weiss J, Kwaan MR, Nutt CL, Louis DN, Stiles CD, Rowitch DH. The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. J Neuropathol Exp Neurol 2004;63(5):499-509.
Gray PA, Fu H, Luo P, Zhao Q, Yu J, Ferrari A, Tenzen T, Yuk DI, Tsung EF, Cai Z, Alberta JA, Cheng LP, Liu Y, Stenman JM, Valerius MT, Billings N, Kim HA, Greenberg ME, McMahon AP, Rowitch DH, Stiles CD, Ma Q. Mouse brain organization revealed through direct genome-scale TF expression analysis. Science 2004;306(5705):2255-7.
Arnett HA, Fancy SP, Alberta JA, Zhao C, Plant SR, Kaing S, Raine CS, Rowitch DH, Franklin RJ, Stiles CD. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science 2004;306(5704):2111-5.
Kho AT, Zhao Q, Cai Z, Butte AJ, Kim JY, Pomeroy SL, Rowitch DH, Kohane IS. Conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of human cancers. Genes Dev 2004;18(6):629-40.
Kenney AM, Cole MD, Rowitch DH. Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 2003;130(1):15-28.
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 connection. Cell 2002;109(1):75-86.
Lu QR, Yuk D, Alberta JA, Zhu Z, Pawlitzky I, Chan J, McMahon AP, Stiles CD, Rowitch DH. Sonic hedgehog--regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron 2000;25(2):317-29.