Daniel Scoles, PhD
Research Associate Professor of Neurology
Dr. Daniel Scoles received his B.S. in Biochemistry from 
University of California, Riverside in 1987 and Ph.D. in population genetics from the College of William and Mary in Virginia in 1994. He then conducted postdoctoral training with Stefan Pulst, M.D. at Cedars-Sinai Medical Center in Los Angeles, and joined the research faculty of the UCLA School of Medicine in 1999. Between 2004-2008 Dr. Scoles was Director of Laboratory Research in the Division of Gynecologic Oncology at Cedars-Sinai Medical Center. Dr. Scoles joined the faculty of the University of Utah in July of 2008. Dr. Scoles is a basic scientist with two primary areas of interest including neurofibromatosis 2 (NF2) and spinocerebellar ataxia 2 (SCA2).
Neurofibromatosis 2 (NF2) is an inherited benign tumor disorder caused by mutations in the NF2 gene, characterized by bilateral vestibular schwannomas and meningiomas. The NF2 gene is also the most commonly mutated gene in sporadic benign tumors. Since 1994 Dr. Scoles has studied the function of the protein product of the NF2 gene, merlin. Highlights of his discoveries on NF2 include merlin interaction with βΙΙ-spectrin that appears to be key to its regulation of cytoskeleton structure, merlin regulation of cell surface receptors such as EGFR by way of interaction with hepatocyte growth factor receptor substrate (HRS) which controls endosomal trafficking, and merlin regulation of protein translation through binding eukaryotic translation initiation factor 3 subunit c (eIF3c). Dr. Scoles has also shown that eIF3c is overexpressed in various tumor types including meningiomas, gliomas, ovarian and breast cancers. These studies demonstrate eIF3c as a possible therapeutic target for NF2 patient tumors as well as for a variety of cancers.
Spinocerebellar ataxia 2 (SCA2) is a type of autosomal dominant cerebellar ataxia. Cerebellar ataxias are characterized by progressive degeneration of the cerebellum and brain stem, caused by polyglutamine expansion in the SCA2 protein encoded by the atxn2 gene. Dr. Scoles is currently characterizing the atxn2 promoter using novel reporter plasmids, and is also using high-throughput compound screening to identify new drugs for the treatment of SCA2 that alter atxn2 promoter activity. Experimental drugs will be tested in knockout and transgenic SCA2 mice that we are preparing or have already established. These studies are being conducted collaboratively with members of the laboratory of Stefan Pulst at the University of Utah, Department of Neurology.
Dr. Scoles is author to 22 publications and three book chapters. He is member of the National Neurofibromatosis Foundation, American Academy of Neurology, American Association for Cancer Research and has been a grant reviewer for the Department of Defense since 1999. Dr. Scoles has been awarded investigative grants from the National Institutes of Health, the Department of Defense Neurofibromatosis Program and the James S. McDonnell Foundation.
Selected Publications
- Li, A., Scoles, D.R., Armstrong, K., and Karlan, B. Androgen receptor cytosine-adenine-guanine repeat polymorphisms modulate EGFR signaling in epithelial ovarian carcinomas. Gynecologic Oncology 109(2):220-5; 2008.
- Scoles, D.R. The merlin interacting proteins reveal multiple targets for NF2 therapy. Biochimica et Biophysica Acta, Reviews on Cancer 1785:32-54; 2008.
- Scoles, D.R., Das, A., and Pulst, S.M. “Primary Tumors of the Nervous System”, Emory and Rimoin’s Principals and Practice of Medical Genetics, (eds: Rimoin, D.L., Connor, J.M., Pyeritz, R.E., Korf, B.R.) 5th Edition, Chapter 131, pp. 2879-2894, Livingstone Churchill, New York, 2007.
- Scoles, D.R., Yong, W., Qin, Y., Wawrowsky, K. and Pulst, S.M. Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor 3 subunit c (eIF3c). Human Molecular Genetics. 15:1059-1070; 2006.
- Huynh, D.P., Scoles, D.R., Nguyen, D., and Pulst, S.M. The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI. Human Molecular Genetics 12(20):2587-97; 2003.
- Scoles, D.R., Huynh, D.P., Chen, M.S., Burke, S.P., Gutmann, D.H., and Pulst, S.M. The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate. Human Molecular Genetics 9:1567-1574; 2000.
- Scoles, D.R., Huynh, D., Morcos, P.A., Coulsell, E., Robinson, G., Tamanoi, F., and Pulst, S.M. The neurofibromatosis 2 tumor suppressor schwannomin interacts with βII-spectrin. Nature Genetics 18:354-359; 1998.