Daniel R. Scoles

Daniel R. Scoles, PhD

Languages spoken: English

Academic Information

Departments Primary - Neurology

Research Interests

  • Spinocerebellar Ataxias
  • Amyotrophic Lateral Sclerosis
  • Parkinson's Disease

Daniel R. Scoles, PhD, is a professor of neurology. His scientific training includes biochemistry, genetics of natural populations, and neurology with emphasis on brain tumor research. Dr. Scoles’s research objectives are centered on the identification of drugs for the treatment of spinocerebellar ataxia type 2 (SCA2), Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and Parkinson’s disease. Drug discovery methodologies used by Dr. Scoles include quantitative high throughput screening (qHTS) and antisense oligonucleotide screening. His research is promoted by collaborative partnerships with industry and the National Institutes of Health (NCATS). He also investigates molecular mechanisms of disease gene expression control aimed at identifying new therapeutic targets and understanding drug action. He is currently supported by grants from the NINDS.



SPECIALTIES: Drug Discovery, Molecular Cellular and Organismal Biology.

Education History

Postdoctoral Fellowship Cedars-Sinai Medical Center
 Postdoctoral Fellow
Cedars- Sinai Medical Center
 Postdoctoral Fellow
Doctoral Training The College of William and Mary
 PhD
The College of William and Mary
 MA
Undergraduate University of California Riverside
 BS

Selected Publications

Journal Article

  1. Figueroa KP, Gross C, Buena-Atienza E, Paul S, Gandelman M, Kakar N, Sturm M, Casadei N, Admard J, Park J, Zhlke C, Hellenbroich Y, Pozojevic J, Balachandran S, Hndler K, Zittel S, Timmann D, Erdlenbruch F, Herrmann L, Feindt T, Zenker M, Klopstock T, Dufke C, Scoles DR, Koeppen A, Spielmann M, Riess O, Ossowski S, Haack TB, Pulst SM (in press). A GGC repeat expansion in ZFHX3 encoding poly-glycine causes spinocerebellar ataxia type 4 and impairs autophagy. Nat Genet.
  2. Figueroa KP, Gross C, Buena-Atienza E, Paul S, Gandelman M, Haack T, Kakar N, Sturm M, Casadei N, Admard J, Park J, Zhlke C, Hellenbroich Y, Pozojevic J, Balachandran S, Hndler K, Zittel S, Timmann D, Erdlenbruch F, Herrmann L, Feindt T, Zenker M, Dufke C, Hbener-Schmid J, Scoles DR, Koeppen A, Ossowski S, Spielmann M, Riess O, Pulst SM (2023). GGC expansion in ZFHX3 causes SCA4 and impairs autophagy. medRxiv, doi.org/10.1101/2023.10.26.23297560.
  3. Bartelt LC, Switonski PM, Adamek G, Carvalho J, Duvick LA, Jarrah SI, McLoughlin HS, Scoles DR, Pulst SM, Orr HT, Hull C, Lowe CB, La Spada AR (2023). Purkinje-Enriched snRNA-seq in SCA7 Cerebellum Reveals Zebrin Identity Loss as a Central Feature of Polyglutamine Ataxias. bioRxiv, 2023 May 11:2023.03.19.533345.
  4. Paul S, Dansithong W, Gandelman M, Figueroa KP, Zu T, Ranum LPW, Scoles DR, Pulst SM (2023). Staufen Impairs Autophagy in Neurodegeneration. Annals of Neurology, 93(2), 398-416.
  5. Figueroa KP, Anderson CJ, Paul S, Dansithong W, Gandelman M, Scoles DR, Pulst, SM (2023). Slc9a6 mutation causes Purkinje cell loss and ataxia in the shaker rat. . Human Molecular Genetics.
  6. Scoles DR, Gandelman M, Paul S, Dexheimer T, Dansithong W, Figueroa KP, Pflieger LT, Redlin S, Kales SC, Sun H, Maloney D, Damoiseaux R, Henderson MJ, Simeonov A, Jadhav A, Pulst SM (2022). A quantitative high-throughput screen identifies compounds that lower expression of the SCA2-and ALS-associated gene ATXN2. Journal of Biological Chemistry, 298(8), 102228.
  7. Gandelman M, Dansithong W, Kales SC, Paul S, Maag G, Aoyama E, Zakharov A, Rai G, Dexheimer T, Whitehill BM, Sun H, Jadhav A, Simeonov A, Henderson MJ, Huynh DP, Pulst SM, Scoles DR (2021). The AKT modulator A-443654 reduces α-synuclein expression and normalizes ER stress and autophagy. J Biol Chem, 279(4), 101191.
  8. Sundberg CA, Lakk M, Paul S, P Figueroa K, Scoles DR, Pulst SM, Kriaj D (2021). The RNA-binding protein and stress granule component ATAXIN-2 is expressed in mouse and human tissues associated with glaucoma pathogenesis. J Comp Neurol, 530(2), 537-552.
  9. Paul S, Dansithong W, Figueroa KP, Gandelman M, Scoles DR, Pulst SM (2021). Staufen1 in human neurodegeneration. Ann Neurol, 89(6), 1114-1128.
  10. Chopra R, Bushart DD, Cooper JP, Yellajoshyula D, Morrison LM, Huang H, Handler HP, Man LJ, Dansithong W, Scoles DR, Pulst SM, Orr HT, Shakkottai VG (2020). Altered Capicua expression drives regional Purkinje neuron vulnerability through ion channel gene dysregulation in spinocerebellar ataxia type 1. Hum Mol Genet, 29(19), 3249-3265.
  11. Gandelman M, Dansithong W, Figueroa KP, Paul S, Scoles DR, Pulst SM (2020). Staufen 1 amplifies pro-apoptotic activation of the unfolded protein response. 27(10), 2942-2951.
  12. Scoles DR, Dansithong W, Pflieger LT, Paul S, Gandelman M, Figueroa KP, Rigo F, Bennett CF, Pulst SM (2020). ALS-associated genes in SCA2 mouse spinal cord transcriptomes. Hum Mol Genet, 29(10), 1658-1672.
  13. Gandelman M, Dansithong W, Figueroa KP, Paul S, Scoles DR, Pulst SM (2019). Staufen 1 amplifies pro-apoptotic activation of the unfolded protein response. bioRxiv, 820225.
  14. Paul S, Dansithong W, Gandelman M, Zu T, Ranum LP, Figueroa KP, Scoles DR, Pulst SM (2019). Staufen blocks autophagy in neurodegeneration. 659649.
  15. Brown AS, Meera P, Altindag B, Chopra R, Perkins EM, Paul S, Scoles DR, Tarapore E, Magri J, Huang H, Jackson M, Shakkottai VG, Otis TS, Pulst SM, Atwood SX, Oro AE (2018). MTSS1/Src family kinase dysregulation underlies multiple inherited ataxias. Proc Natl Acad Sci U S A, 115(52), E12407-E12416. (Read full article)
  16. Paul S, Dansithong W, Figueroa KP, Scoles DR, Pulst SM (2018). Staufen1 links RNA stress granules and autophagy in neurodegeneration. Nat Commun, 9(1), 3648.
  17. Brown AS, Meera P, Altindag B, Chopra R, Perkins E, Paul S, Scoles DR, Tarapore E, Jackson M, Shakkottai VG, Otis TS, Pulst SM, Atwood SX, Oro AE (2018). MTSS1/Src family kinase Dysregulation Underlies Multiple Inherited Ataxias. bioRxiv, 338046.
  18. Wen J, Scoles DR, Facelli JC (2017). Molecular dynamics analysis of aggregation propensity of polyglutamine segments. PLoS One, 12(5), e0178333.
  19. Pflieger LT, Dansithong W, Paul S, Scoles DR, Figueroa K, Meera P, Otis TS, Facelli JC, Pulst SM (2017). Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2. Hum Mol Genet, 26(16), 3069-3080.
  20. Scoles DR, Meera P, Schneider M, Paul S, Dansithong W, Figueroa KP, Hung G, Rigo F, Bennett CF, Otis TS, Pulst SM (2017). Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. Nature, 544(7650), 362-366.
  21. Wen J, Scoles DR, Facelli J (2016). Effects of the enlargement of poly-glutamine segments on the structure and folding of ataxin-2 and ataxin-3 proteins. J Biomol Struct Dyn, May 20, 1-16.
  22. Figueroa KP, Paul S, Cal T, Lopreiato R, Karan S, Frizzarin M, Ames D, Zanni G, Brini M, Dansithong W, Milash B, Scoles DR, Carafoli E, Pulst SM (2016). Spontaneous Shaker rat mutant – A new model for X-linked tremor ataxia. Dis Model Mech, 9(5), 553-562.
  23. Dansithong W, Paul S, Ho MHT, Scoles DR, Pulst SM, Huynh DP (2015). Generation of SCNA cell models using zinc finger nuclease (ZFN) technology for efficient high-throughput drug screening. PLoS One, 10(8), e0136930.
  24. Scoles DR, Ho MHT, Dansithong W, Pflieger LT, Petersen LW, Thai KK, Pulst SM (2015). Repeat associated non-AUG translation (RAN translation) in ATXN2 is dependent on sequence downstream of the ATXN2 CAG repeat. PLoS One, 10(6), e0128769.
  25. Dansithong W, Paul S, Figueroa KP, Rinehart MD, Wiest S, Pfleiger LT, Scoles DR, Pulst SM (2015). Ataxin-2 regulates RGS8 translation in a new BAC-SCA2 transgenic mouse model. PLoS Genet, 11(4), e1005182.
  26. Wen J, Scoles DR, Facelli JC (2014). Structure Prediction of Polyglutamine Disease Proteins: Comparison of Methods. BMC Bioinformatics, 15 Suppl 7.
  27. Matilla-Dueas A, Ashizawa T, Brice A, Magri S, McFarland KN, Pandolfo M, Pulst SM, Riess O, Rubinsztein DC, Schmidt J, Schmidt T, Scoles DR, Stevanin G, Taroni F, Underwood BR, Snchez I (2014). Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias. Cerebellum, 13(2), 269-302.
  28. Scoles DR, Pflieger LT, Thai KK, Hansen ST, Dansithong W, Pulst SM (2012). ETS1 regulates expression of ATXN2. Hum Mol Genet, 21(23), 5048-65.
  29. Scoles DR, Xu X, Wang H, Tran H, Taylor-Harding B, Li A, Karlan BY (2010). Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein. Gynecol Oncol, 116(1), 109-116.
  30. Elmore RG, Ioffe Y, Scoles DR, Karlan BY, Li AJ (2008). Impact of statin therapy on survival in epithelial ovarian cancer. Gynecol Oncol, 111(1), 102-105.
  31. Walsh CS, Ogawa S, Karahashi H, Scoles DR, Pavelka JC, Tran H, Miller CW, Kawamata N, Ginther C, Dering J, Sanada M, Nannya Y, Slamon DJ, Koeffler HP, Karlan BY (2008). ERCC5 is a novel biomarker of ovarian cancer prognosis. J Clin Oncol, 26(18), 2952-8. (Read full article)
  32. Li AJ, Scoles DR, Armstrong KU, Karlan BY (2008). Androgen receptor cytosine-adenine-guanine repeat polymorphisms modulate EGFR signaling in epithelial ovarian carcinomas. Gynecol Oncol, 109(2), 220-5. (Read full article)
  33. Scoles DR, Pavelka J, Cass I, Tran H, Baldwin RL, Armstrong K, Karlan BY (2007). Characterization of CSOC 882, a novel immortalized ovarian cancer cell line expressing EGFR, HER2, and activated AKT. Gynecol Oncol, 104(1), 120-8. (Read full article)
  34. Scoles DR, Yong WH, Qin Y, Wawrowsky K, Pulst SM (2006). Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c). Hum Mol Genet, 15(7), 1059-70. (Read full article)
  35. Oh M-K, Scoles DR, Pulst SM (2005). DNA microarray analysis of immediate response to EGF treatment in rat schwannoma cells. Biotechnol Bioprocess Eng, 10(5), 444-450.
  36. Scoles DR, Qin Y, Nguyen V, Gutmann DH, Pulst SM (2005). HRS inhibits EGF receptor signaling in the RT4 rat schwannoma cell line. Biochem Biophys Res Commun, 335(2), 385-92. (Read full article)
  37. Oh MK, Scoles DR, Haipek C, Strand AD, Gutmann DH, Olson JM, Pulst SM (2003). Genetic heterogeneity of stably transfected cell lines revealed by expression profiling with oligonucleotide microarrays. J Cell Biochem, 90(5), 1068-78. (Read full article)
  38. Qin Y, Pulst S, Scoles DR (2003). The NF2 tumor suppressor schwannomin interacts with the eukaryotic initiation factor 3 (eIF3) subunit p110. Conference Paper. Am J Hum Genet, 73(3), 201.
  39. Huynh DP, Scoles DR, Nguyen D, Pulst SM (2003). The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI. Hum Mol Genet, 12(20), 2587-97. (Read full article)
  40. Scoles DR, Nguyen VD, Qin Y, Sun CX, Morrison H, Gutmann DH, Pulst SM (2002). Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling. Hum Mol Genet, 11(25), 3179-89. (Read full article)
  41. Sun CX, Haipek C, Scoles DR, Pulst SM, Giovannini M, Komada M, Gutmann DH (2002). Functional analysis of the relationship between the neurofibromatosis 2 tumor suppressor and its binding partner, hepatocyte growth factor-regulated tyrosine kinase substrate. Hum Mol Genet, 11(25), 3167-78. (Read full article)
  42. Scoles DR, Chen M, Pulst SM (2002). Effects of Nf2 missense mutations on schwannomin interactions. Biochem Biophys Res Commun, 290(1), 366-74. (Read full article)
  43. Gutmann DH, Haipek CA, Burke SP, Sun CX, Scoles DR, Pulst SM (2001). The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the "open" conformation and suppresses cell growth and motility. Hum Mol Genet, 10(8), 825-34. (Read full article)
  44. Huynh DP, Scoles DR, Ho TH, Del Bigio MR, Pulst SM (2000). Parkin is associated with actin filaments in neuronal and nonneural cells. Ann Neurol, 48(5), 737-44. (Read full article)
  45. Scoles DR, Huynh DP, Chen MS, Burke SP, Gutmann DH, Pulst SM (2000). The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate. Hum Mol Genet, 9(11), 1567-74. (Read full article)
  46. Austin HM, Scoles D, Abell AJ (1999). Morphometric separation of annual cohorts within mid-Atlantic bluefish, Pomatomus saltatrix, using discriminant function analysis. 97, 411-420.
  47. Scoles DR, Huynh DP, Morcos PA, Coulsell ER, Robinson NG, Tamanoi F, Pulst SM (1998). Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin. Nat Genet, 18(4), 354-9. (Read full article)
  48. Scoles DR, Graves JE, Collette BB (1998). Global phylogeography of mackerels of the genus Scomber. 96, 823-842.
  49. Scoles DR, Baser ME, Pulst SM (1996). A missense mutation in the neurofibromatosis 2 gene occurs in patients with mild and severe phenotypes. Neurology, 47(2), 544-6. (Read full article)
  50. Scoles DR, Graves JE (1993). Genetic analysis of the population structure of yellowfin tuna Thunnus albacares in the Pacific Ocean. 91, 690-698.
  51. Graves JE, McDowell JR, Beardsley AM, Scoles DR (1992). Stock structure of the bluefish, Pomatomus saltatrix, along the mid-Atlantic coast. 90, 703-710.

Review

  1. Paul S, Scoles DR, Pulst SM (2023). Effects of STAU1/staufen1 on autophagy in neurodegenerative diseases. [Review]. Autophagy.
  2. Paul S, Scoles DR, Pulst SM (2021). Splicing Control of Pontocerebellar Development. [Review]. 109(2), 191-192.
  3. Scoles DR, Pulst SM (2019). Antisense therapies for movement disorders. [Review]. Mov Disord, 34(8), 1112-9.
  4. Scoles DR, Minikel EV, Pulst SM (2019). Antisense oligonucleotides: A primer. [Review]. Neurol Genet, 5(2), e323.
  5. Scoles DR, Pulst SM (2018). Oligonucleotide therapeutics in neurodegenerative diseases. [Review]. RNA Biol, 15(6), 707-14.
  6. Scoles DR (2008). The merlin interacting proteins reveal multiple targets for NF2 therapy. [Review]. Biochim Biophys Acta, 1785(1), 32-54.

Book Chapter

  1. Scoles DR, Pulst SM (2018). "Spinocerebellar Ataxia Type 2". In Luís Pereira de Almeida and Clévio Nóbrega (Eds.), Polyglutamine Disorders. Adv Exp Med Biol, Vol. 1049 (pp. 175-195). Springer.
  2. Huynh DP, Dansithong W, Scoles DR, Pulst SM (2018). "Advanced Gene-Targeting Methods to Generate Cell Line Models that Preserve Native Regulatory Elements for Efficient High-Throughput Drug Screenings". In Development of Biomedical Engineering in Vietnam. Springer Nature Singapore Pte Ltd.
  3. Scoles DR, Das A, Pulst SM (2007). “Primary Tumors of the Nervous System”. In Rimoin DL, Connor JM, Pyeritz RE, Korf BR (Eds.), Emory and Rimoin's Principals and Practice of Medical Genetics (5th Edition, pp. 2879-2894). New York: Livingstone Churchill.
  4. Scoles DR, Pulst SM (2003). “Brain Tumors, Genetics”. In Aminoff M, Daroff R (Eds.), Encyclopedia of the Neurological Sciences (1, pp. 470-472). San Diego: Academic Press.
  5. Pulst SM, Scoles DR (2002). “Primary Tumors of the Nervous System”. In Rimoin DL, Connor JM, Pyeritz RE, Korf BR (Eds.), Emory and Rimoin's Principals and Practice of Medical Genetics (4th Edition, pp. 3231-3249). New York: Livingstone Churchill.

Patent

  1. Daniel Scoles, Sharan Paul, Stefan Pulst (2018). Staufen1 Agents and Associated Methods. U.S. Patent No. 11723912. Washington, D.C.:U.S. Patent and Trademark Office.
  2. Bennett CF, Freier SM, Pulst SM, Scoles DR, Hung G (2018). Methods for modulating ataxin 2 expression. U.S. Patent No. 10533178. Washington, D.C.:U.S. Patent and Trademark Office.
  3. Bennett CF, Freier SM, Pulst SM, Scoles DR, Hung G (2015). Methods for modulating ataxin 2 expression. U.S. Patent No. 10006027. Washington, D.C.:U.S. Patent and Trademark Office.
  4. Pulst SM, Scoles DR (2002). Schwannomin-binding proteins. Inventors. U.S. Patent No. 6960650. Washington, D.C.:U.S. Patent and Trademark Office.
  5. Pulst SM, Scoles DR (1997). Nucleic acid encoding schwannomin-binding proteins and products related thereto. U.S. Patent No. 6376174. Washington, D.C.:U.S. Patent and Trademark Office.