Laura P W Ranum

Laura P W Ranum,

Kitzman Family Professor Of Molecular Genetics And Microbiology; Director Center For NeuroGenetics

Department: Molecular Genetics & Microbiology
Business Phone: (352) 294-5209
Business Email: ranum@ufl.edu

Research Profile

Open Researcher and Contributor ID (ORCID)

0000-0001-9808-9661

Areas of Interest
  • Amyotrophic Lateral Sclerosis
  • Gene Discovery
  • Genetics of Neurodegenerative Disease
  • Multiple System Atrophy (MSA)
  • Myotonic Dystrophy
  • Neurodegenerative diseases
  • Neuropathology of Neurodegenerative diseases
  • Repeat Expansion Diseases
  • Spinocerebellar Ataxia

Publications

2021
CCG•CGG interruptions in high penetrance SCA8 families increase RAN translation and protein toxicity
BioRx. [DOI] 10.1101/2021.02.08.430311.
2021
Repeat length increases disease penetrance and severity in C9orf72 ALS/FTD BAC transgenic mice
Human Molecular Genetics. 29(24):3900-3918 [DOI] 10.1093/hmg/ddaa279.
2020
Antibody Therapy Targeting RAN Proteins Rescues C9 ALS/FTD Phenotypes in C9orf72 Mouse Model.
Neuron. 105(4):645-662.e11 [DOI] 10.1016/j.neuron.2019.11.007. [PMID] 31831332.
2020
Loss of MBNL1 induces RNA misprocessing in the thymus and peripheral blood.
Nature communications. 11(1) [DOI] 10.1038/s41467-020-15962-x. [PMID] 32332745.
2020
Metformin inhibits RAN translation through PKR pathway and mitigates disease inC9orf72ALS/FTD mice
Proceedings of the National Academy of Sciences. 117(31):18591-18599 [DOI] 10.1073/pnas.2005748117. [PMID] 32690681.
2020
Survival and Motor Phenotypes in FVB C9-500 ALS/FTD BAC Transgenic Mice Reproduced by Multiple Labs.
Neuron. 108(4):784-796.e3 [DOI] 10.1016/j.neuron.2020.09.009. [PMID] 33022226.
2019
Repeat-Associated Non-ATG Translation: Molecular Mechanisms and Contribution to Neurological Disease.
Annual review of neuroscience. 42:227-247 [DOI] 10.1146/annurev-neuro-070918-050405. [PMID] 30909783.
2019
Repeat-associated non-AUG (RAN) translation: insights from pathology.
Laboratory investigation; a journal of technical methods and pathology. 99(7):929-942 [DOI] 10.1038/s41374-019-0241-x. [PMID] 30918326.
2018
All in the Family: Repeats and ALS/FTD.
Trends in neurosciences. 41(5):247-250 [DOI] 10.1016/j.tins.2018.03.010. [PMID] 29703376.
2018
Altered levels of the splicing factor muscleblind modifies cerebral cortical function in mouse models of myotonic dystrophy.
Neurobiology of disease. 112:35-48 [DOI] 10.1016/j.nbd.2018.01.003. [PMID] 29331264.
2018
Intron retention induced by microsatellite expansions as a disease biomarker.
Proceedings of the National Academy of Sciences of the United States of America. 115(16):4234-4239 [DOI] 10.1073/pnas.1716617115. [PMID] 29610297.
2018
Repeat-associated non-ATG (RAN) translation.
The Journal of biological chemistry. 293(42):16127-16141 [DOI] 10.1074/jbc.R118.003237. [PMID] 30213863.
2018
Repeat-Associated Non-ATG Translation in Neurological Diseases.
Cold Spring Harbor perspectives in biology. 10(12) [DOI] 10.1101/cshperspect.a033019. [PMID] 29891563.
2018
SCA8 RAN polySer protein preferentially accumulates in white matter regions and is regulated by eIF3F.
The EMBO journal. 37(19) [DOI] 10.15252/embj.201899023. [PMID] 30206144.
2017
A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.
PloS one. 12(5) [DOI] 10.1371/journal.pone.0173565. [PMID] 28467418.
2017
Mutant Huntingtin Disrupts the Nuclear Pore Complex.
Neuron. 94(1):93-107.e6 [DOI] 10.1016/j.neuron.2017.03.023. [PMID] 28384479.
2017
New developments in RAN translation: insights from multiple diseases.
Current opinion in genetics & development. 44:125-134 [DOI] 10.1016/j.gde.2017.03.006. [PMID] 28365506.
2017
RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2.
Neuron. 95(6):1292-1305.e5 [DOI] 10.1016/j.neuron.2017.08.039. [PMID] 28910618.
2016
C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD.
Neuron. 90(3):521-34 [DOI] 10.1016/j.neuron.2016.04.005. [PMID] 27112499.
2015
Genome modification leads to phenotype reversal in human myotonic dystrophy type 1 induced pluripotent stem cell-derived neural stem cells.
Stem cells (Dayton, Ohio). 33(6):1829-38 [DOI] 10.1002/stem.1970. [PMID] 25702800.
2015
MBNL Sequestration by Toxic RNAs and RNA Misprocessing in the Myotonic Dystrophy Brain.
Cell reports. 12(7):1159-68 [DOI] 10.1016/j.celrep.2015.07.029. [PMID] 26257173.
2015
RAN Translation in Huntington Disease.
Neuron. 88(4):667-77 [DOI] 10.1016/j.neuron.2015.10.038. [PMID] 26590344.
2014
Hippocampal sclerosis dementia with the C9ORF72 hexanucleotide repeat expansion.
Neurobiology of aging. 35(10):2419.e17-21 [DOI] 10.1016/j.neurobiolaging.2014.04.009. [PMID] 24819148.
2014
Mutant β-III spectrin causes mGluR1α mislocalization and functional deficits in a mouse model of spinocerebellar ataxia type 5.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 34(30):9891-904 [DOI] 10.1523/JNEUROSCI.0876-14.2014. [PMID] 25057192.
2014
Repeat associated non-ATG (RAN) translation: new starts in microsatellite expansion disorders.
Current opinion in genetics & development. 26:6-15 [DOI] 10.1016/j.gde.2014.03.002. [PMID] 24852074.
2013
Compound Loss of Muscleblind-Like Function in Myotonic Dystrophy
Embo Molecular Medicine. 5:1887-1900
2013
RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia.
Proceedings of the National Academy of Sciences of the United States of America. 110(51):E4968-77 [DOI] 10.1073/pnas.1315438110. [PMID] 24248382.
2013
Repeat-associated non-ATG (RAN) translation in neurological disease.
Human molecular genetics. 22(R1):R45-51 [DOI] 10.1093/hmg/ddt371. [PMID] 23918658.
2013
Robust cytoplasmic accumulation of phosphorylated TDP-43 in transgenic models of tauopathy.
Acta neuropathologica. 126(1):39-50 [DOI] 10.1007/s00401-013-1123-8. [PMID] 23666556.
2012
C9ORF72 repeat expansion in amyotrophic lateral sclerosis in the Kii peninsula of Japan.
Archives of neurology. 69(9):1154-8 [DOI] 10.1001/archneurol.2012.1219. [PMID] 22637429.
2012
Clinical and genetic features of spinocerebellar ataxia type 8.
Handbook of clinical neurology. 103:493-505 [DOI] 10.1016/B978-0-444-51892-7.00031-0. [PMID] 21827909.
2012
GGCCTG repeats put a hex on Purkinje cells and motor neurons in SCA36.
Neurology. 79(4):302-3 [DOI] 10.1212/WNL.0b013e31826043d9. [PMID] 22744663.
2012
Mouse model of muscleblind-like 1 overexpression: skeletal muscle effects and therapeutic promise.
Human molecular genetics. 21(21):4645-54 [DOI] 10.1093/hmg/dds306. [PMID] 22846424.
2012
Mutational origin of Machado-Joseph disease in the Australian Aboriginal communities of Groote Eylandt and Yirrkala.
Archives of neurology. 69(6):746-51 [DOI] 10.1001/archneurol.2011.2504. [PMID] 22351852.
2012
Spinocerebellar ataxia type 5.
Handbook of clinical neurology. 103:451-9 [DOI] 10.1016/B978-0-444-51892-7.00028-0. [PMID] 21827906.
2011
Dutch myotonic dystrophy type 2 patients and a North-African DM2 family carry the common European founder haplotype.
European journal of human genetics : EJHG. 19(5):567-70 [DOI] 10.1038/ejhg.2010.233. [PMID] 21224892.
2011
Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13).
PloS one. 6(3) [DOI] 10.1371/journal.pone.0017811. [PMID] 21479265.
2011
Non-ATG-initiated translation directed by microsatellite expansions.
Proceedings of the National Academy of Sciences of the United States of America. 108(1):260-5 [DOI] 10.1073/pnas.1013343108. [PMID] 21173221.
2010
[Double the trouble: bidirectional expression of the SCA8 CAG/CTG expansion mutation – evidence for RNA and protein gain of function effects].
Rinsho shinkeigaku = Clinical neurology. 50(11):982-3 [PMID] 21921535.
View on: PubMed
2010
Molecular genetic advances in neurological disease: special review issue.
Human molecular genetics. 19(R1):R1-3 [DOI] 10.1093/hmg/ddq193. [PMID] 20484169.
2010
Spectrin mutations that cause spinocerebellar ataxia type 5 impair axonal transport and induce neurodegeneration in Drosophila.
The Journal of cell biology. 189(1):143-58 [DOI] 10.1083/jcb.200905158. [PMID] 20368622.
2009
RNA gain-of-function in spinocerebellar ataxia type 8.
PLoS genetics. 5(8) [DOI] 10.1371/journal.pgen.1000600. [PMID] 19680539.
2009
SNP haplotype mapping in a small ALS family.
PloS one. 4(5) [DOI] 10.1371/journal.pone.0005687. [PMID] 19479031.
2008
Mutagenic roles of DNA “repair” proteins in antibody diversity and disease-associated trinucleotide repeat instability.
DNA repair. 7(7):1135-54 [DOI] 10.1016/j.dnarep.2008.03.014. [PMID] 18485833.
2007
Asian origin for the worldwide-spread mutational event in Machado-Joseph disease.
Archives of neurology. 64(10):1502-8 [PMID] 17923634.
View on: PubMed
2006
Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8.
Nature genetics. 38(7):758-69 [PMID] 16804541.
View on: PubMed
2006
DM2 intronic expansions: evidence for CCUG accumulation without flanking sequence or effects on ZNF9 mRNA processing or protein expression.
Human molecular genetics. 15(11):1808-15 [PMID] 16624843.
View on: PubMed
2006
Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation.
Journal of medical genetics. 43(6):527-30 [PMID] 16236810.
View on: PubMed
2006
RNA-mediated neuromuscular disorders.
Annual review of neuroscience. 29:259-77 [PMID] 16776586.
View on: PubMed
2006
Spectrin mutations cause spinocerebellar ataxia type 5.
Nature genetics. 38(2):184-90 [PMID] 16429157.
View on: PubMed
2005
Genetics and molecular pathogenesis of the myotonic dystrophies.
Current neurology and neuroscience reports. 5(1):55-9 [PMID] 15676109.
View on: PubMed
2005
RNA pathogenesis of the myotonic dystrophies.
Neuromuscular disorders : NMD. 15(1):5-16 [PMID] 15639115.
View on: PubMed
2004
Hairpin structure-forming propensity of the (CCTG.CAGG) tetranucleotide repeats contributes to the genetic instability associated with myotonic dystrophy type 2.
The Journal of biological chemistry. 279(40):41715-26 [PMID] 15292165.
View on: PubMed
2004
Myotonic dystrophy: RNA pathogenesis comes into focus.
American journal of human genetics. 74(5):793-804 [PMID] 15065017.
View on: PubMed
2004
Pathogenic RNA repeats: an expanding role in genetic disease.
Trends in genetics : TIG. 20(10):506-12 [PMID] 15363905.
View on: PubMed
2004
Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype analysis of 37 families with ataxia.
American journal of human genetics. 75(1):3-16 [PMID] 15152344.
View on: PubMed
2003
Myotonic dystrophy type 2: human founder haplotype and evolutionary conservation of the repeat tract.
American journal of human genetics. 73(4):849-62 [PMID] 14505273.
View on: PubMed
2003
Repeat analysis pooled isolation and detection (RAPID) cloning of microsatellite expansions.
Methods in molecular biology (Clifton, N.J.). 217:61-71 [PMID] 12491921.
View on: PubMed
2002
Dominantly inherited, non-coding microsatellite expansion disorders.
Current opinion in genetics & development. 12(3):266-71 [PMID] 12076668.
View on: PubMed
2002
Myotonic dystrophy: clinical and molecular parallels between myotonic dystrophy type 1 and type 2.
Current neurology and neuroscience reports. 2(5):465-70 [PMID] 12169228.
View on: PubMed
2001
Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9.
Science (New York, N.Y.). 293(5531):864-7 [PMID] 11486088.
View on: PubMed
2000
Reply-
Nature genetics. 24(3) [PMID] 10700169.
View on: PubMed
2000
SCA8 CTG repeat: en masse contractions in sperm and intergenerational sequence changes may play a role in reduced penetrance.
Human molecular genetics. 9(14):2125-30 [PMID] 10958651.
View on: PubMed
1999
A nonpathogenic GAAGGA repeat in the Friedreich gene: implications for pathogenesis.
Neurology. 53(8):1854-7 [PMID] 10563639.
View on: PubMed
1999
An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8)
Nature genetics. 21(4):379-84 [PMID] 10192387.
View on: PubMed
1999
Clinical and genetic characteristics of a five-generation family with a novel form of myotonic dystrophy (DM2).
Neuromuscular disorders : NMD. 9(1):19-27 [PMID] 10063831.
View on: PubMed
1999
Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7.
Human molecular genetics. 8(9):1657-64 [PMID] 10441328.
View on: PubMed

Grants

Sep 2020 ACTIVE
Identifying and understanding the role of repeat RNAs and RAN proteins in Alzheimer's disease
Role: Other
Funding: NATL INST OF HLTH NIA
Apr 2020 – Mar 2021
An endobody vaccine against a combination of RAN proteins as a therapeutic approach in a C9 ALS BAC mouse model
Role: Principal Investigator
Funding: JOHNS HOPKINS UNIV
Jan 2020 ACTIVE
Provenance Initiatives Fund at the Center for NeuroGenetics
Role: Principal Investigator
Funding: UF FOU
Nov 2019 ACTIVE
C9ORF72 ALS: Endobody vaccine for the treatment of C9 ALS/FTD
Role: Other
Funding: AMYOTROPHIC LATERAL SCLEROSIS ASSOC
Sep 2019 ACTIVE
Therapeutic Potential of Metformin, an FDA-approved drug, and PKR Targeting for C9orf72 ALS
Role: Principal Investigator
Funding: US ARMY MED RES AND MATERIAL COM
Dec 2018 – Jan 2021
Presymptomatic biomarkers of C9-ALS/FTD
Role: Principal Investigator
Funding: AMYOTROPHIC LATERAL SCLEROSIS ASSOC
Sep 2018 – Apr 2020
Assessment of endobody vaccine for effectiveness and ability to generate C9 RAN antibodies
Role: Principal Investigator
Funding: UNITED NEUROSCIENCE LIMITED
Aug 2018 ACTIVE
The contribution of RAN proteins to C9ORF72 ALS/FTD
Role: Principal Investigator
Funding: MUSCULAR DYSTROPHY ASSO
Aug 2018 – Feb 2021
C9ORF72 ALS: Proof of biology for antibody treatment in C9-ALS mouse model
Role: Principal Investigator
Funding: BIOGEN MA INC
Feb 2018 – Feb 2020
Therapeutic potential of CRISPR-Cas9 in C9ORF72-repeat deletion strategy in C9ORF72 BAC transgenic mice
Role: Principal Investigator
Funding: CRISPR THERAPEUTICS AG
Jan 2018 – Dec 2019
Molecular characterization of RNA and RAN protein effects in DM2
Role: Other
Funding: WYCK FOUNDATION
Jul 2017 ACTIVE
Neurodegenerative disease research
Role: Principal Investigator
Funding: UF FOU
Jul 2017 ACTIVE
University of Florida/National Ataxia Foundation Brain Donation Program
Role: Principal Investigator
Funding: NATL ATAXIA FOUNDATION
May 2017 – Dec 2020
Therapeutic potential of CRISPR-Cas9 in C9ORF72 ALS/FTD-repeat deletion and transcriptional repression strategies in humanized C9ORF72 BAC transgenic mice
Role: Principal Investigator
Funding: TARGET ALS FOUNDATION via CRISPR THERAPEUTICS AG
Jan 2017 – Jun 2020
Developing human-derived antibodies to target dipeptide-repeat protein toxicity in C9orf72 disease
Role: Principal Investigator
Funding: TARGET ALS FOUNDATION
Jan 2017 – Jun 2020
Nuclear Export Inhibitor KPT-350 for C9orf72 and Sporadic ALS
Role: Principal Investigator
Funding: TARGET ALS FOUNDATION
Aug 2016 ACTIVE
Molecular Characterization of ALS/FTD in a novel C9orf72 BAC mouse model.
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Aug 2016 – Jul 2018
Molecular characterization & antibody therapy in a novel C9orf72 BAC mouse model
Role: Principal Investigator
Funding: MUSCULAR DYSTROPHY ASSO
Aug 2016 – Oct 2017
Developing a high-throughput screening assay for identification of small molecules that selectively target transcription of G4C2/G2C4 repeat expansions in the gene C9ORF72 in ALS
Role: Other
Funding: AMYOTROPHIC LATERAL SCLEROSIS ASSOC
Mar 2016 – Mar 2018
The Therapeutic Efficacy of Neurimmunes Human Derived Recombinant Antibodies in C9orf72 Transgenic Mouse Models
Role: Principal Investigator
Funding: NEURIMMUNE AG
Mar 2016 – Apr 2021
neurodegenerative disease research
Role: Principal Investigator
Funding: UF FOU
Jan 2016 ACTIVE
Molecular genetic characterization of SCA8
Role: Principal Investigator
Funding: UF FOU
Jan 2016 ACTIVE
Molecular Genetics of the G4C2 expansion mutation in ALS/FTD
Role: Principal Investigator
Funding: UF FOU
Jan 2016 – Dec 2016
ASO targeting of bidirectional transcripts and RAN translation in SCA8
Role: Principal Investigator
Funding: NATL ATAXIA FOUNDATION
Dec 2015 – Dec 2020
Brainstorming microsatellite expansion diseases symposium
Role: Principal Investigator
Funding: UF FOU
Aug 2015 ACTIVE
Molecular Genetic Characterization of SCA8
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Jan 2015 – Jan 2018
MBI Research Program MGOLD1
Role: Principal Investigator
Funding: UF FOU
Sep 2013 – Jun 2019
Myotonic Dystrophy: Molecular Pathophysiology and CNS Effects
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Jul 2013 ACTIVE
Center for NeuroGenetics
Role: Principal Investigator
Funding: UF FOU
Jul 2013 – Jun 2019
Matching Funds for PPG Project Titled: "Myotonic Dystrophy: Molecular Pathophysiology and CNS Effects"
Role: Principal Investigator
Funding: FL CLINICAL PRACTICE ASSO
May 2013 – Apr 2016
Repeat associated non-ATG (RAN) Translation in C9ORF72 ALS/FTD
Role: Principal Investigator
Funding: COLUMBIA UNIVERSITY

Patents

Published May 2016
Methods for Diagnosing Huntington's Disease
#US18/0292416
Published March 2014
Use and Treatment of Di-Amino Acid Repeat-Containing Proteins Associated with ALS
#US2016-0025747-A1

Teaching Profile

Courses Taught
2018
GMS7980 Research for Doctoral Dissertation
2018
GMS7979 Advanced Research
2016-2017
GMS6750 Molecular Pathobiology of Neural Disease

Contact Details

Phones:
Business:
(352) 294-5209
Emails:
Business:
ranum@ufl.edu