Dawn S. Chandler, Ph.D.
The Ohio State University School of Medicine
Nationwide Children's Research Institute
Center for Childhood Cancer
700 Children's Drive, Rm. WA5023
Columbus, OH 43205
Phone: (614) 722-5598
Fax: (614) 722-5895
Education & Training:
University of Texas Health Science Center, Houston, TX, 1998
Ph.D. in Biomedical Sciences
M.D. Anderson Cancer Center, Houston, TX,
2002 Postdoctoral Fellow Human Genetics
Anderson Cancer Center, Houston, TX, 2004 Postdoctoral Fellow Cancer
Our lab is interested in the regulation of pre-mRNA splicing and
how disruption of this regulation can lead to pediatric diseases such as
cancer. Current work in our lab elucidates alternative splicing as
a novel mechanism by which cellular injury can control the activity of
p53 and how changes in the regulation of splicing can lead to tumorigenesis. The
transcription factor p53 is known to induce G1 arrest of the cell cycle
and/or apoptosis. MDM2 is one of the most critical regulators of p53. Using
in vitro biochemical assays and genetically engineered mouse models we
are currently investigating differential RNA splicing of both the MDM2
and p53 pre-mRNAs and investigating the roles of each in normal cell function
as well as disease.
Another pediatric disease Proximal Spinal Muscular Atrophy
(SMA), the leading genetic cause of infant mortality in humans, is in
part due to a mutation that affects splicing of a duplicated gene that
controls neuronal growth (SMN2). We are interested in generating viable mouse
models for human SMA with the long-term goal of testing candidate therapies
that target the human SMN2 gene. To do this, we are generating mouse
lines that will be utilized to answer many questions pertaining the therapeutic
possibilities of SMN replacement, splicing correction by drug or antisense
treatment, and the correct timing of such therapies.
- Bebee, T.W., Dominguez, C.E., Samadzadeh-Tarighat, S. Akehurst, K.L., Chandler, D.S. Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model. Hum. Mol. Genet., 19:4301-13, 2012.
- Pierson, C.R., Dulin-Smith, A.N., Durban, A.N., Marshall, M.L., Marshall, J.T., Snyder, A.D., Naiyer, N., Gladman, J.T., Chandler, D.S., Lawlor, M.W., Buj-Bello, A., Dowling, J.J., Beggs, A.H. Modeling the Human MTM1p.R69C Mutation in Murine MTM1 Results in Exon 4 Skipping and a Less Severe Myotubular Myopathy Phenotype. Hum. Mol. Genet., 21:8110825, 2012.
Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC, NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma, Cancer Cell, 14(5): 369-381, 2008.
Chandler, D.S., Singh, R.K., Caldwell, L.C., Bitler, J.L., and Lozano, G. Genotoxic stress induces coordinately regulated alternative splicing of the p53 modulators MDM2 and MDM4. Cancer Research, 66: 9502-9508, 2006.