Daniel R. Scoles

Daniel R. Scoles, PhD

Languages spoken: English

Academic Information

Departments Primary - Neurology

Daniel R. Scoles, PhD, Professor and Dr. John P. Punke Endowed Chair in the Department of Neurology. His education includes biochemistry, population genetics, and neuro-oncology. His research focuses on therapeutic development for neurodegenerative disorders, including spinocerebellar ataxia type 2 (SCA2), Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease. Dr. Scoles employs quantitative high-throughput screening (qHTS), antisense oligonucleotide technologies, and gene expression modulation strategies to identify novel therapeutic targets and elucidate disease mechanisms. His work is strengthened by collaborations with industry partners and the NIH National Center for Advancing Translational Sciences (NCATS). Supported by NINDS grants, Dr. Scoles leads programs in drug discovery, molecular and cellular biology, and translational neuroscience, with the overarching aim of advancing new treatments for devastating neurological diseases.


SPECIALTIES: Drug Discovery, Molecular Cellular and Organismal Biology.

Education History

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

Selected Publications

Journal Article

  1. Qin Y, Pulst S, Scoles D (2003). The NF2 tumor suppressor schwannomin interacts with the eukaryotic initiation factor 3 (eIF3) subunit p110. Conference Paper. American journal of human genetics, 73(3), 201.
  2. Huynh DP, Scoles DR, Ho TH, Del Bigio MR, Pulst S (2000). Parkin is associated with actin filaments in neuronal and nonneural cells. Annals of neurology, 48(5), 737-44. (Read full article)
  3. Paul S, Dansithong W, Figueroa KP, Gandelman M, Scoles DR, Pulst SM (2021). Staufen1 in human neurodegeneration. Annals of neurology, 89(6), 1114-1128.
  4. Scoles DR, Chen M, Pulst S (2002). Effects of Nf2 missense mutations on schwannomin interactions. Biochemical and biophysical research communications, 290(1), 366-74. (Read full article)
  5. Scoles DR, Qin Y, Nguyen V, Gutmann DH, Pulst S (2005). HRS inhibits EGF receptor signaling in the RT4 rat schwannoma cell line. Biochemical and biophysical research communications, 335(2), 385-92. (Read full article)
  6. Wen J, Scoles DR, Facelli (2016). Effects of the enlargement of poly-glutamine segments on the structure and folding of ataxin-2 and ataxin-3 proteins. Journal of biomolecular structure & dynamics, May 20, 1-16.
  7. Scoles DR, Huynh DP, Chen MS, Burke SP, Gutmann DH, Pulst S (2000). The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate. Human molecular genetics, 9(11), 1567-74. (Read full article)
  8. Gutmann DH, Haipek CA, Burke SP, Sun CX, Scoles DR, Pulst S (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. Human molecular genetics, 10(8), 825-34. (Read full article)
  9. Sun CX, Haipek C, Scoles DR, Pulst SM, Giovannini M, Komada M, Gutmann D (2002). Functional analysis of the relationship between the neurofibromatosis 2 tumor suppressor and its binding partner, hepatocyte growth factor-regulated tyrosine kinase substrate. Human molecular genetics, 11(25), 3167-78. (Read full article)
  10. Scoles DR, Nguyen VD, Qin Y, Sun CX, Morrison H, Gutmann DH, Pulst S (2002). Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling. Human molecular genetics, 11(25), 3179-89. (Read full article)
  11. Huynh DP, Scoles DR, Nguyen D, Pulst S (2003). The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI. Human molecular genetics, 12(20), 2587-97. (Read full article)
  12. Scoles DR, Yong WH, Qin Y, Wawrowsky K, Pulst S (2006). Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c). Human molecular genetics, 15(7), 1059-70. (Read full article)
  13. Scoles DR, Pflieger LT, Thai KK, Hansen ST, Dansithong W, Pulst S (2012). ETS1 regulates expression of ATXN2. Human molecular genetics, 21(23), 5048-65.
  14. 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. Human molecular genetics, 26(16), 3069-3080.
  15. Scoles DR, Dansithong W, Pflieger LT, Paul S, Gandelman M, Figueroa KP, Rigo F, Bennett CF, Pulst S (2020). ALS-associated genes in SCA2 mouse spinal cord transcriptomes. Human molecular genetics, 29(10), 1658-1672.
  16. 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. Human molecular genetics, 29(19), 3249-3265.
  17. Scoles DR, Huynh DP, Morcos PA, Coulsell ER, Robinson NG, Tamanoi F, Pulst S (1998). Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin. Nature genetics, 18(4), 354-9. (Read full article)
  18. Scoles DR, Pavelka J, Cass I, Tran H, Baldwin RL, Armstrong K, Karlan B (2007). Characterization of CSOC 882, a novel immortalized ovarian cancer cell line expressing EGFR, HER2, and activated AKT. Gynecologic oncology, 104(1), 120-8. (Read full article)
  19. Li AJ, Scoles DR, Armstrong KU, Karlan B (2008). Androgen receptor cytosine-adenine-guanine repeat polymorphisms modulate EGFR signaling in epithelial ovarian carcinomas. Gynecologic oncology, 109(2), 220-5. (Read full article)
  20. 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. Gynecologic oncology, 116(1), 109-116.
  21. Elmore RG, Ioffe Y, Scoles DR, Karlan BY, Li AJ (2008). Impact of statin therapy on survival in epithelial ovarian cancer. Gynecologic oncology, 111(1), 102-105.
  22. 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. The Journal of biological chemistry, 279(4), 101191.
  23. Oh MK, Scoles DR, Haipek C, Strand AD, Gutmann DH, Olson JM, Pulst S (2003). Genetic heterogeneity of stably transfected cell lines revealed by expression profiling with oligonucleotide microarrays. Journal of cellular biochemistry, 90(5), 1068-78. (Read full article)
  24. Sundberg CA, Lakk M, Paul S, P Figueroa K, Scoles DR, Pulst SM, Kri'aj D (2021). The RNA-binding protein and stress granule component ATAXIN-2 is expressed in mouse and human tissues associated with glaucoma pathogenesis. The Journal of comparative neurology, 530(2), 537-552.
  25. 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 B (2008). ERCC5 is a novel biomarker of ovarian cancer prognosis. Journal of clinical oncology, 26(18), 2952-8. (Read full article)
  26. Scoles DR, Meera P, Schneider M, Paul S, Dansithong W, Figueroa KP, Hung G, Rigo F, Bennett CF, Otis TS, Pulst S (2017). Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. Nature, 544(7650), 362-366.
  27. Scoles DR, Baser ME, Pulst S (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)
  28. 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 A (2018). MTSS1/Src family kinase dysregulation underlies multiple inherited ataxias. Proceedings of the National Academy of Sciences of the United States of America, 115(52), E12407-E12416. (Read full article)
  29. Wen J, Scoles DR, Facelli J (2014). Structure Prediction of Polyglutamine Disease Proteins: Comparison of Methods. BMC bioinformatics, 15 Suppl 7,
  30. Matilla-Dueñas 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, Sánchez I (2014). Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias. Cerebellum (London, England), 13(2), 269-302.
  31. 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 genetics, 11(4), e1005182.
  32. Oh M-K, Scoles DR, Pulst S (2005). DNA microarray analysis of immediate response to EGF treatment in rat schwannoma cells. Biotechnology and bioprocess engineering, 10(5), 444-450.
  33. Scoles DR, Ho MHT, Dansithong W, Pflieger LT, Petersen LW, Thai KK, Pulst S (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.
  34. Dansithong W, Paul S, Ho MHT, Scoles DR, Pulst SM, Huynh D (2015). Generation of SCNA cell models using zinc finger nuclease (ZFN) technology for efficient high-throughput drug screening. PloS one, 10(8), e0136930.
  35. Wen J, Scoles DR, Facelli J (2017). Molecular dynamics analysis of aggregation propensity of polyglutamine segments. PloS one, 12(5), e0178333.
  36. Figueroa KP, Paul S, Calì 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. Disease models & mechanisms, 9(5), 553-562.
  37. Paul S, Dansithong W, Figueroa KP, Scoles DR, Pulst S (2018). Staufen1 links RNA stress granules and autophagy in neurodegeneration. Nature communications, 9(1), 3648.
  38. Graves JE, McDowell JR, Beardsley AM, Scoles D (1992). Stock structure of the bluefish, Pomatomus saltatrix, along the mid-Atlantic coast. 90, 703-710.
  39. Scoles DR, Graves J (1993). Genetic analysis of the population structure of yellowfin tuna Thunnus albacares in the Pacific Ocean. 91, 690-698.
  40. Scoles DR, Graves JE, Collette B (1998). Global phylogeography of mackerels of the genus Scomber. 96, 823-842.
  41. Austin HM, Scoles D, Abell A (1999). Morphometric separation of annual cohorts within mid-Atlantic bluefish, Pomatomus saltatrix, using discriminant function analysis. 97, 411-420.
  42. Paul S, Dansithong W, Gandelman M, Zu T, Ranum LP, Figueroa KP, Scoles DR, Pulst SM (2019). Staufen blocks autophagy in neurodegeneration. 659649,
  43. 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,
  44. 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 A (2018). MTSS1/Src family kinase Dysregulation Underlies Multiple Inherited Ataxias. bioRxiv, 338046,
  45. 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.
  46. 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,
  47. 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.
  48. Figueroa KP, Gross C, Buena-Atienza E, Paul S, Gandelman M, Kakar N, Sturm M, Casadei N, Admard J, Park J, Zühlke C, Hellenbroich Y, Pozojevic J, Balachandran S, Händler 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 (2024). A GGC repeat expansion in ZFHX3 encoding poly-glycine causes spinocerebellar ataxia type 4 and impairs autophagy. Nature genetics,
  49. 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,
  50. Figueroa KP, Gross C, Buena-Atienza E, Paul S, Gandelman M, Haack T, Kakar N, Sturm M, Casadei N, Admard J, Park J, Zühlke C, Hellenbroich Y, Pozojevic J, Balachandran S, Händler K, Zittel S, Timmann D, Erdlenbruch F, Herrmann L, Feindt T, Zenker M, Dufke C, Hübener-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,
  51. 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 S (2022). A quantitative high-throughput screen identifies compounds that lower expression of the SCA2-and ALS-associated gene ATXN2. The Journal of biological chemistry, 298(8), 102228. (Read full article)
  52. Paul S, Dansithong W, Gandelman M, Figueroa KP, Scoles DR, Pulst S (2024). Cerebellar Micro-RNA Profile in a Mouse Model of Spinocerebellar Ataxia Type 2. Neurology. Genetics, 10(2), e200144. (Read full article)
  53. Sahay S, Wen J, Scoles DR, Simeonov A, Dexheimer TS, Jadhav A, Kales SC, Sun H, Pulst SM, Facelli JC, Jones D (2025). Identifying Molecular Properties of Ataxin-2 Inhibitors for Spinocerebellar Ataxia Type 2 Utilizing High-Throughput Screening and Machine Learning. Biology, 14(5), (Read full article)
  54. 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 A (2023). Purkinje-Enriched snRNA-seq in SCA7 Cerebellum Reveals Zebrin Identity Loss as a Central Feature of Polyglutamine Ataxias. bioRxiv, (Read full article)

Review

  1. Scoles D (2008). The merlin interacting proteins reveal multiple targets for NF2 therapy. Biochimica et biophysica acta, 1785(1), 32-54.
  2. Scoles DR, Pulst S (2019). Antisense therapies for movement disorders. Movement disorders, 34(8), 1112-9.
  3. Scoles DR, Pulst S (2018). Oligonucleotide therapeutics in neurodegenerative diseases. RNA biology, 15(6), 707-14.
  4. Scoles DR, Minikel EV, Pulst S (2019). Antisense oligonucleotides: A primer. Neurology. Genetics, 5(2), e323.
  5. Paul S, Scoles DR, Pulst SM (2021). Splicing Control of Pontocerebellar Development. 109(2), 191-192.
  6. Paul S, Scoles DR, Pulst SM (2023). Effects of STAU1/staufen1 on autophagy in neurodegenerative diseases. Autophagy, 19(9), 2607-2608.
  7. Scoles DR, Pulst SM (2024). Control of innate immunity and lipid biosynthesis in neurodegeneration. Frontiers in molecular medicine, 17(1402055),

Book Chapter

  1. Pulst SM, Scoles D (2002). ¿Primary Tumors of the Nervous System¿. 3231-3249.
  2. Scoles DR, Pulst S (2003). ¿Brain Tumors, Genetics¿. 1, 470-472.
  3. Scoles DR, Das A, Pulst S (2007). ¿Primary Tumors of the Nervous System¿. 2879-2894.
  4. Scoles DR, Pulst S (2018). "Spinocerebellar Ataxia Type 2". 175-195.
  5. Huynh DP, Dansithong W, Scoles DR, Pulst S (2018). "Advanced Gene-Targeting Methods to Generate Cell Line Models that Preserve Native Regulatory Elements for Efficient High-Throughput Drug Screenings".