Matthew Disney

Matthew Disney, Ph.D.

Chair, Department Of Chemistry

Department: SR-CHEM-DISNEY LAB
Business Phone: (561) 228-2000
Business Email: mdisney@ufl.edu

About Matthew Disney

Additional Positions:
Associate Professor, Chemistry
2010 – 2014 · Scripps Research
Assistant Professor
2005 – 2010 · University at Buffalo
Postdoctoral Fellow
2002 – 2005 · Swiss Federal Institute of Technology Zurich (ETH)

Accomplishments

Recipient
2021 · The ACS 2022 Nobel Laureate Signature Award for Graduate Education in Chemistry
Awarded
2019 · The Raymond and Beverly Sackler International Prize in Chemistry
Awarded
2018 · BioFlorida's Weaver H. Gaines Entrepreneur of the Year
The Barry Cohen Prize
2018 · Medicinal Chemistry Section of the Israel Chemical Society and Teva Pharmaceutical Industries.
Outstanding Mentor Award
2017 · Scripps Florida
Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry
2016 ·
Blavatnik Young Scientists Award Finalist
2015-2017 ·
NIH Director’s Pioneer Award
2015 · National Institutes of Health
David W. Robertson Award in Medicinal Chemistry
2014 · American Chemical Society’s Division of Medicinal Chemistry
Eli Lilly Award in Biological Chemistry
2013 · American Chemical Society
Excellence Award in the field of Research in Science and Technology
2013 · India-US Chamber of Commerce, Inc.
David Gin Award in Carbohydrate Chemistry
2012 · American Chemical Society
Dreyfus Teacher-Scholar Award
2010-2015 ·
Excellent Scholar, Young Investigator Award
2010 · University at Buffalo
Research Corporation Cottrell Scholar Award
2008-2010 ·
NYSTAR JD Watson Young Investigator Award
2007-2009 ·
Camille and Henry Dreyfus New Faculty Award
2005-2010 ·
Second Year Roche Foundation Postdoctoral Fellowship
2004-2005 · Swiss Federal Institute of Technology
Roche Foundation Postdoctoral Fellowship
2003-2004 · Swiss Federal Institute of Technology
Arnold Weissberger Memorial Fellow
2001-2002 · University of Rochester
Elon Huntington Hooker Memorial Fellow
2000-2001 · University of Rochester
Sherman-Clark Memorial Fellow
1997-1999 · University of Rochester
Eric A. Batista Award
1997 · University of Maryland at College Park
Howard Hughes Medical Institute Undergraduate Research Fellow
1995-1997 · University of Maryland at College Park

Research Profile

The Disney group develops rational approaches to design selective therapeutics from only genome sequence. One of the major advantages that genome sequencing efforts potentially provides is advancing patient-specific therapies, yet such developments have been only sparsely reported. We have developed general approach to provide lead Targeted Therapeutics and Precise Medicines that target RNAs that cause disease broadly and include rare neuromuscular (muscular dystrophy), neurodegenerative (Alzheimer’s, ALS), infectious diseases as well as difficult-to-treat cancers (breast, pancreatic, prostate, and others), and infectious diseases that can emerge through seasonal exposures. Designed compounds have demonstrated activity in human derived cellular disease models as well as pre-clinical animal models of disease. We train the next-generation of scientists to ensure our work has an exponential impact in studying disease biology and leveraging it into making Precision Medicines.

To achieve these goals, we developed a proprietary platform dubbed Inforna over the past 13 years. It merges chemoinformatics and RNA structure to identify lead compounds that target an RNA of interest; that is, Inforna houses a database of RNA three dimensional motifs that bind small molecule medicines, identified via an experimental library-versus-library screen. The bioinformatics pipeline rapidly and accurately identifies disease-associated RNA sequences that adopt targetable three-dimensional folds by comparison to the database. This pipeline has been validated in various peer-review publications that demonstrated that the platform can be used to target RNAs that cause neuromuscular, neurodegenerative, and infectious diseases as well as difficult-to-treat cancers in pre-clinical animal models. Additionally, lead small molecule medicines can also be rapidly developed into compounds that recruit cellular nucleases to selectively destroy the RNAs that cause these diseases in a catalytic and substoichiometric manner (e.g. one molecule of the small molecule cleaves more than one molecule of the RNA target) coined RIBOTACs. Two of the major perceived concerns in the area of RNA-targeted small molecules are selectivity and potency. We have broadly demonstrated that these issues can be rapidly overcome via rational design and fragment assembly.

Key recent advances include:

(i) Sequence-based drug design across the human transcriptome to provide precision lead medicines

(ii) Small molecule cleavage of RNAs (RIBOTACS) in a catalytic and sub-stoichiometric manner via recruitment of cellular nucleases

(iii) Tools and technologies to study ligand binding capacity of RNAs across the transcriptome (Chem-CLIP and Ribo-SNAP)

(iv) Showing broad classes of known drugs target RNA and that their activity may be traced to targeting non-coding RNA

(v) Chemical biology approaches to understand RNA biology. We uncovered the mechanistic cause of Fragule X-Syndrome and Autism and also can define precisely the effect that non-coding RNAs have on the proteome.

(vi) Study druggability broadly. We have the ability to answer fundamental questions about how druggable the genome really is. Thus, we have launched the Druggable Transcriptome Project.

Publications

2022
A structure-specific small molecule inhibits a miRNA-200 family member precursor and reverses a type 2 diabetes phenotype.
Cell chemical biology. 29(2):300-311.e10 [DOI] 10.1016/j.chembiol.2021.07.006. [PMID] 34320373.
2022
Bioinformatic Searching for Optimal RNA Targets of Dimeric Compounds Informs Design of a MicroRNA-27a Inhibitor.
ACS chemical biology. 17(1):5-10 [DOI] 10.1021/acschembio.1c00395. [PMID] 34898169.
2022
DNA-encoded library versus RNA-encoded library selection enables design of an oncogenic noncoding RNA inhibitor.
Proceedings of the National Academy of Sciences of the United States of America. 119(6) [DOI] 10.1073/pnas.2114971119. [PMID] 35110406.
2022
Rational Approach to Identify RNA Targets of Natural Products Enables Identification of Nocathiacin as an Inhibitor of an Oncogenic RNA.
ACS chemical biology. 17(2):474-482 [DOI] 10.1021/acschembio.1c00952. [PMID] 35044149.
2021
A Druglike Small Molecule that Targets r(CCUG) Repeats in Myotonic Dystrophy Type 2 Facilitates Degradation by RNA Quality Control Pathways.
Journal of medicinal chemistry. 64(12):8474-8485 [DOI] 10.1021/acs.jmedchem.1c00414. [PMID] 34101465.
2021
A Few Revolutions of the RNA World in ACS Publications.
Journal of the American Chemical Society. 143(32) [DOI] 10.1021/jacs.1c06885. [PMID] 34369145.
2021
A glimpse at the glycoRNA world.
Cell. 184(12):3080-3081 [DOI] 10.1016/j.cell.2021.05.025. [PMID] 34115968.
2021
A map of the SARS-CoV-2 RNA structurome.
NAR genomics and bioinformatics. 3(2) [DOI] 10.1093/nargab/lqab043. [PMID] 34046592.
2021
A Small Molecule Exploits Hidden Structural Features within the RNA Repeat Expansion That Causes c9ALS/FTD and Rescues Pathological Hallmarks.
ACS chemical neuroscience. 12(21):4076-4089 [DOI] 10.1021/acschemneuro.1c00470. [PMID] 34677935.
2021
A Small Molecule that Binds an RNA Repeat Expansion Stimulates Its Decay via the Exosome Complex.
Cell chemical biology. 28(1):34-45.e6 [DOI] 10.1016/j.chembiol.2020.10.007. [PMID] 33157036.
2021
Affecting RNA biology genome-wide by binding small molecules and chemically induced proximity.
Current opinion in chemical biology. 62:119-129 [DOI] 10.1016/j.cbpa.2021.03.006. [PMID] 34118759.
2021
Massively Parallel Optimization of the Linker Domain in Small Molecule Dimers Targeting a Toxic r(CUG) Repeat Expansion.
ACS medicinal chemistry letters. 12(6):907-914 [DOI] 10.1021/acsmedchemlett.1c00027. [PMID] 34141068.
2021
Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit.
The Journal of infectious diseases. 224(Supplement_1):S1-S21 [DOI] 10.1093/infdis/jiab305. [PMID] 34111271.
2021
Reprogramming of Protein-Targeted Small-Molecule Medicines to RNA by Ribonuclease Recruitment.
Journal of the American Chemical Society. 143(33):13044-13055 [DOI] 10.1021/jacs.1c02248. [PMID] 34387474.
2021
Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G4C2) repeat expansion in vitro and in vivo ALS models.
Science translational medicine. 13(617) [DOI] 10.1126/scitranslmed.abd5991. [PMID] 34705518.
2021
Small molecule 1a reduces FMRpolyG-mediated toxicity in in vitro and in vivo models for FMR1 premutation.
Human molecular genetics. 30(17):1632-1648 [DOI] 10.1093/hmg/ddab143. [PMID] 34077515.
2021
Systematically Studying the Effect of Small Molecules Interacting with RNA in Cellular and Preclinical Models.
ACS chemical biology. 16(7):1111-1127 [DOI] 10.1021/acschembio.1c00014. [PMID] 34166593.
2020
A general fragment-based approach to identify and optimize bioactive ligands targeting RNA.
Proceedings of the National Academy of Sciences of the United States of America. 117(52):33197-33203 [DOI] 10.1073/pnas.2012217117. [PMID] 33318191.
2020
A Toxic RNA Catalyzes the Cellular Synthesis of Its Own Inhibitor, Shunting It to Endogenous Decay Pathways.
Cell chemical biology. 27(2):223-231.e4 [DOI] 10.1016/j.chembiol.2020.01.003. [PMID] 31981476.
2020
A Toxic RNA Templates the Synthesis of Its Own Fluorogenic Inhibitor by Using a Bio-orthogonal Tetrazine Ligation in Cells and Tissues.
ACS chemical biology. 15(7):1820-1825 [DOI] 10.1021/acschembio.0c00417. [PMID] 32551539.
2020
An in silico map of the SARS-CoV-2 RNA Structurome.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2020.04.17.045161. [PMID] 32511381.
2020
Design of a small molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold-small molecule interactions.
Nature chemistry. 12(10):952-961 [DOI] 10.1038/s41557-020-0514-4. [PMID] 32839603.
2020
Design of small molecules targeting RNA structure from sequence.
Chemical Society reviews. 49(20):7252-7270 [DOI] 10.1039/d0cs00455c. [PMID] 32935689.
2020
Design, Optimization, and Study of Small Molecules That Target Tau Pre-mRNA and Affect Splicing.
Journal of the American Chemical Society. 142(19):8706-8727 [DOI] 10.1021/jacs.0c00768. [PMID] 32364710.
2020
Gini Coefficients as a Single Value Metric to Define Chemical Probe Selectivity.
ACS chemical biology. 15(8):2031-2040 [DOI] 10.1021/acschembio.0c00486. [PMID] 32568503.
2020
Hexanucleotide Repeat Expansions in c9FTD/ALS and SCA36 Confer Selective Patterns of Neurodegeneration In Vivo.
Cell reports. 31(5) [DOI] 10.1016/j.celrep.2020.107616. [PMID] 32375043.
2020
How We Think about Targeting RNA with Small Molecules.
Journal of medicinal chemistry. 63(17):8880-8900 [DOI] 10.1021/acs.jmedchem.9b01927. [PMID] 32212706.
2020
Macrocyclization of a Ligand Targeting a Toxic RNA Dramatically Improves Potency.
Chembiochem : a European journal of chemical biology. 21(22):3229-3233 [DOI] 10.1002/cbic.202000445. [PMID] 32649032.
2020
Optimization of the Linker Domain in a Dimeric Compound that Degrades an r(CUG) Repeat Expansion in Cells.
Journal of medicinal chemistry. 63(14):7827-7839 [DOI] 10.1021/acs.jmedchem.0c00558. [PMID] 32657583.
2020
Precise Targeted Cleavage of a r(CUG) Repeat Expansion in Cells by Using a Small-Molecule-Deglycobleomycin Conjugate.
ACS chemical biology. 15(4):849-855 [DOI] 10.1021/acschembio.0c00036. [PMID] 32186845.
2020
Progress toward the development of the small molecule equivalent of small interfering RNA.
Current opinion in chemical biology. 56:63-71 [DOI] 10.1016/j.cbpa.2020.01.001. [PMID] 32036231.
2020
Small molecule recognition of disease-relevant RNA structures.
Chemical Society reviews. 49(19):7167-7199 [DOI] 10.1039/d0cs00560f. [PMID] 32975549.
2020
Small molecule targeting of RNA structures in neurological disorders.
Annals of the New York Academy of Sciences. 1471(1):57-71 [DOI] 10.1111/nyas.14051. [PMID] 30964958.
2020
Small-molecule targeted recruitment of a nuclease to cleave an oncogenic RNA in a mouse model of metastatic cancer.
Proceedings of the National Academy of Sciences of the United States of America. 117(5):2406-2411 [DOI] 10.1073/pnas.1914286117. [PMID] 31964809.
2020
Structural Features of Small Molecules Targeting the RNA Repeat Expansion That Causes Genetically Defined ALS/FTD.
ACS chemical biology. 15(12):3112-3123 [DOI] 10.1021/acschembio.0c00049. [PMID] 33196168.
2020
Structure-Specific Cleavage of an RNA Repeat Expansion with a Dimeric Small Molecule Is Advantageous over Sequence-Specific Recognition by an Oligonucleotide.
ACS chemical biology. 15(2):485-493 [DOI] 10.1021/acschembio.9b00958. [PMID] 31927948.
2020
Target-Directed Approaches for Screening Small Molecules against RNA Targets.
SLAS discovery : advancing life sciences R & D. 25(8):869-894 [DOI] 10.1177/2472555220922802. [PMID] 32419578.
2020
Targeted Degradation of the Oncogenic MicroRNA 17-92 Cluster by Structure-Targeting Ligands.
Journal of the American Chemical Society. 142(15):6970-6982 [DOI] 10.1021/jacs.9b13159. [PMID] 32233464.
2020
Targeting the SARS-CoV-2 RNA Genome with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders.
ACS central science. 6(10):1713-1721 [DOI] 10.1021/acscentsci.0c00984. [PMID] 33140033.
2020
Translation of the intrinsically disordered protein α-synuclein is inhibited by a small molecule targeting its structured mRNA.
Proceedings of the National Academy of Sciences of the United States of America. 117(3):1457-1467 [DOI] 10.1073/pnas.1905057117. [PMID] 31900363.
2019
A cross-linking approach to map small molecule-RNA binding sites in cells.
Bioorganic & medicinal chemistry letters. 29(12):1532-1536 [DOI] 10.1016/j.bmcl.2019.04.001. [PMID] 30987892.
2019
A Designed Small Molecule Inhibitor of a Non-Coding RNA Sensitizes HER2 Negative Cancers to Herceptin.
Journal of the American Chemical Society. 141(7):2960-2974 [DOI] 10.1021/jacs.8b10558. [PMID] 30726072.
2019
Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy.
Molecular neurodegeneration. 14(1) [DOI] 10.1186/s13024-019-0310-z. [PMID] 30767771.
2019
Adding Broccoli to the Biosensor Menu.
Cell chemical biology. 26(4):463-465 [DOI] 10.1016/j.chembiol.2019.04.004. [PMID] 31002799.
2019
Computational Investigation of RNA A-Bulges Related to the Microtubule-Associated Protein Tau Causing Frontotemporal Dementia and Parkinsonism.
The journal of physical chemistry. B. 123(1):57-65 [DOI] 10.1021/acs.jpcb.8b09139. [PMID] 30517788.
2019
Identifying and validating small molecules interacting with RNA (SMIRNAs).
Methods in enzymology. 623:45-66 [DOI] 10.1016/bs.mie.2019.04.027. [PMID] 31239057.
2019
Methods to identify and optimize small molecules interacting with RNA (SMIRNAs).
Drug discovery today. 24(10):2002-2016 [DOI] 10.1016/j.drudis.2019.06.019. [PMID] 31356880.
2019
Precise small-molecule cleavage of an r(CUG) repeat expansion in a myotonic dystrophy mouse model.
Proceedings of the National Academy of Sciences of the United States of America. 116(16):7799-7804 [DOI] 10.1073/pnas.1901484116. [PMID] 30926669.
2019
RNA structural analysis of the MYC mRNA reveals conserved motifs that affect gene expression.
PloS one. 14(6) [DOI] 10.1371/journal.pone.0213758. [PMID] 31206539.
2019
Targeted Degradation of a Hypoxia-Associated Non-coding RNA Enhances the Selectivity of a Small Molecule Interacting with RNA.
Cell chemical biology. 26(8):1180-1186.e5 [DOI] 10.1016/j.chembiol.2019.04.008. [PMID] 31130520.
2019
Targeting RNA with Small Molecules To Capture Opportunities at the Intersection of Chemistry, Biology, and Medicine.
Journal of the American Chemical Society. 141(17):6776-6790 [DOI] 10.1021/jacs.8b13419. [PMID] 30896935.
2019
The Hairpin Form of r(G4C2)exp in c9ALS/FTD Is Repeat-Associated Non-ATG Translated and a Target for Bioactive Small Molecules.
Cell chemical biology. 26(2):179-190.e12 [DOI] 10.1016/j.chembiol.2018.10.018. [PMID] 30503283.
2019
The RNA encoding the microtubule-associated protein tau has extensive structure that affects its biology.
PloS one. 14(7) [DOI] 10.1371/journal.pone.0219210. [PMID] 31291322.
2018
A Massively Parallel Selection of Small Molecule-RNA Motif Binding Partners Informs Design of an Antiviral from Sequence.
Chem. 4(10):2384-2404 [DOI] 10.1016/j.chempr.2018.08.003. [PMID] 30719503.
2018
Approved Anti-cancer Drugs Target Oncogenic Non-coding RNAs.
Cell chemical biology. 25(9):1086-1094.e7 [DOI] 10.1016/j.chembiol.2018.05.015. [PMID] 30251629.
2018
Bleomycin Can Cleave an Oncogenic Noncoding RNA.
Chembiochem : a European journal of chemical biology. 19(1):43-47 [DOI] 10.1002/cbic.201700581. [PMID] 29084369.
2018
Drugging the RNA World.
Cold Spring Harbor perspectives in biology. 10(11) [DOI] 10.1101/cshperspect.a034769. [PMID] 30385607.
2018
Introduction to the Symposium In Print for Laura Kiessling.
Bioorganic & medicinal chemistry. 26(19) [DOI] 10.1016/j.bmc.2018.10.021. [PMID] 30420097.
2018
Introduction.
Bioorganic & medicinal chemistry letters. 28(16):2661-2662 [DOI] 10.1016/j.bmcl.2018.07.013. [PMID] 30029841.
2018
Precise Small Molecule Degradation of a Noncoding RNA Identifies Cellular Binding Sites and Modulates an Oncogenic Phenotype.
ACS chemical biology. 13(11):3065-3071 [DOI] 10.1021/acschembio.8b00827. [PMID] 30375843.
2018
Selective Small Molecule Recognition of RNA Base Pairs.
ACS combinatorial science. 20(8):482-491 [DOI] 10.1021/acscombsci.8b00049. [PMID] 29966095.
2018
Small molecule alteration of RNA sequence in cells and animals.
Bioorganic & medicinal chemistry letters. 28(16):2794-2796 [DOI] 10.1016/j.bmcl.2017.10.034. [PMID] 29079470.
2018
Small Molecule Targeted Recruitment of a Nuclease to RNA.
Journal of the American Chemical Society. 140(22):6741-6744 [DOI] 10.1021/jacs.8b01233. [PMID] 29792692.
2018
Using Genome Sequence to Enable the Design of Medicines and Chemical Probes.
Chemical reviews. 118(4):1599-1663 [DOI] 10.1021/acs.chemrev.7b00504. [PMID] 29322778.
2017
Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA.
ACS central science. 3(3):205-216 [DOI] 10.1021/acscentsci.7b00009. [PMID] 28386598.
2017
Inhibiting Translation One Protein at a Time.
Trends in biochemical sciences. 42(6):412-413 [DOI] 10.1016/j.tibs.2017.04.008. [PMID] 28522328.
2017
Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis.
Science translational medicine. 9(383) [DOI] 10.1126/scitranslmed.aai7866. [PMID] 28356511.
2017
Precise small-molecule recognition of a toxic CUG RNA repeat expansion.
Nature chemical biology. 13(2):188-193 [DOI] 10.1038/nchembio.2251. [PMID] 27941760.
2017
Rapid Generation of miRNA Inhibitor Leads by Bioinformatics and Efficient High-Throughput Screening Methods.
Methods in molecular biology (Clifton, N.J.). 1517:179-198 [PMID] 27924483.
2017
Small Molecule Inhibition of microRNA-210 Reprograms an Oncogenic Hypoxic Circuit.
Journal of the American Chemical Society. 139(9):3446-3455 [DOI] 10.1021/jacs.6b11273. [PMID] 28240549.
2017
Structure and Dynamics of RNA Repeat Expansions That Cause Huntington’s Disease and Myotonic Dystrophy Type 1.
Biochemistry. 56(27):3463-3474 [DOI] 10.1021/acs.biochem.7b00252. [PMID] 28617590.
2016
Analysis of secondary structural elements in human microRNA hairpin precursors.
BMC bioinformatics. 17 [DOI] 10.1186/s12859-016-0960-6. [PMID] 26928172.
2016
Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells.
Annual review of pharmacology and toxicology. 56:123-40 [DOI] 10.1146/annurev-pharmtox-010715-103910. [PMID] 26514201.
2016
Chemistry and Chemical Biology of Therapeutically Important Compounds.
Bioorganic & medicinal chemistry. 24(17) [DOI] 10.1016/j.bmc.2016.06.049. [PMID] 27460698.
2016
Comparison of small molecules and oligonucleotides that target a toxic, non-coding RNA.
Bioorganic & medicinal chemistry letters. 26(11):2605-9 [DOI] 10.1016/j.bmcl.2016.04.025. [PMID] 27117425.
2016
Controlled dehydration improves the diffraction quality of two RNA crystals.
BMC structural biology. 16(1) [PMID] 27809904.
2016
Corrigendum: A Toxic RNA Catalyzes the In Cellulo Synthesis of Its Own Inhibitor.
Angewandte Chemie (International ed. in English). 55(34) [DOI] 10.1002/anie.201605756. [PMID] 27503420.
2016
Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10.
Nature communications. 7 [DOI] 10.1038/ncomms11647. [PMID] 27248057.
2016
Design of a small molecule against an oncogenic noncoding RNA.
Proceedings of the National Academy of Sciences of the United States of America. 113(21):5898-903 [DOI] 10.1073/pnas.1523975113. [PMID] 27170187.
2016
Development of pharmacophore models for small molecules targeting RNA: Application to the RNA repeat expansion in myotonic dystrophy type 1.
Bioorganic & medicinal chemistry letters. 26(23):5792-5796 [DOI] 10.1016/j.bmcl.2016.10.037. [PMID] 27839685.
2016
Inforna 2.0: A Platform for the Sequence-Based Design of Small Molecules Targeting Structured RNAs.
ACS chemical biology. 11(6):1720-8 [DOI] 10.1021/acschembio.6b00001. [PMID] 27097021.
2016
Rational Design of Small Molecules Targeting Oncogenic Noncoding RNAs from Sequence.
Accounts of chemical research. 49(12):2698-2704 [PMID] 27993012.
2016
Small Molecule Recognition and Tools to Study Modulation of r(CGG)(exp) in Fragile X-Associated Tremor Ataxia Syndrome.
ACS chemical biology. 11(9):2456-65 [DOI] 10.1021/acschembio.6b00147. [PMID] 27276216.
2016
Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma.
ACS chemical biology. 11(2):375-80 [DOI] 10.1021/acschembio.5b00615. [PMID] 26551630.
2015
Computational investigation of RNA CUG repeats responsible for myotonic dystrophy 1.
Journal of chemical theory and computation. 11(10):4943-58 [DOI] 10.1021/acs.jctc.5b00728. [PMID] 26500461.
2015
Crystallographic and Computational Analyses of AUUCU Repeating RNA That Causes Spinocerebellar Ataxia Type 10 (SCA10).
Biochemistry. 54(24):3851-9 [DOI] 10.1021/acs.biochem.5b00551. [PMID] 26039897.
2015
Inhibition of Non-ATG Translational Events in Cells via Covalent Small Molecules Targeting RNA.
Journal of the American Chemical Society. 137(16):5336-45 [DOI] 10.1021/ja507448y. [PMID] 25825793.
2015
Preface.
Bioorganic & medicinal chemistry letters. 25(21) [DOI] 10.1016/j.bmcl.2015.08.083. [PMID] 26358161.
2015
RNA Structures as Mediators of Neurological Diseases and as Drug Targets.
Neuron. 87(1):28-46 [DOI] 10.1016/j.neuron.2015.06.012. [PMID] 26139368.
2015
Small molecule chemical probes of microRNA function.
Current opinion in chemical biology. 24:97-103 [DOI] 10.1016/j.cbpa.2014.10.024. [PMID] 25500006.
2015
Small Molecule Inhibition of miR-544 Biogenesis Disrupts Adaptive Responses to Hypoxia by Modulating ATM-mTOR Signaling.
ACS chemical biology. 10(10):2267-76 [DOI] 10.1021/acschembio.5b00265. [PMID] 26181590.
2015
Studying a Drug-like, RNA-Focused Small Molecule Library Identifies Compounds That Inhibit RNA Toxicity in Myotonic Dystrophy.
ACS chemical biology. 10(12):2706-15 [DOI] 10.1021/acschembio.5b00430. [PMID] 26414664.
2014
A toxic RNA catalyzes the in cellulo synthesis of its own inhibitor.
Angewandte Chemie (International ed. in English). 53(41):10956-9 [DOI] 10.1002/anie.201406465. [PMID] 25164984.
2014
Bottom-up design of small molecules that stimulate exon 10 skipping in mutant MAPT pre-mRNA.
Chembiochem : a European journal of chemical biology. 15(14):2041-4 [DOI] 10.1002/cbic.201402069. [PMID] 25115866.
2014
Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS.
Neuron. 83(5):1043-50 [DOI] 10.1016/j.neuron.2014.07.041. [PMID] 25132468.
2014
Discovery of a Biomarker and Lead Small Molecules to Target r(GGGGCC)-Associated Defects in c9FTD/ALS.
Neuron. 84(1) [DOI] 10.1016/j.neuron.2014.09.019. [PMID] 28898625.
2014
Lomofungin and dilomofungin: inhibitors of MBNL1-CUG RNA binding with distinct cellular effects.
Nucleic acids research. 42(10):6591-602 [DOI] 10.1093/nar/gku275. [PMID] 24799433.
2014
Methods to enable the design of bioactive small molecules targeting RNA.
Organic & biomolecular chemistry. 12(7):1029-39 [DOI] 10.1039/c3ob42023j. [PMID] 24357181.
2014
Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome.
Science (New York, N.Y.). 343(6174):1002-5 [DOI] 10.1126/science.1245831. [PMID] 24578575.
2014
Sequence-based design of bioactive small molecules that target precursor microRNAs.
Nature chemical biology. 10(4):291-7 [DOI] 10.1038/nchembio.1452. [PMID] 24509821.
2014
Structure of the myotonic dystrophy type 2 RNA and designed small molecules that reduce toxicity.
ACS chemical biology. 9(2):538-550 [DOI] 10.1021/cb4007387. [PMID] 24341895.
2014
Targeting the r(CGG) repeats that cause FXTAS with modularly assembled small molecules and oligonucleotides.
ACS chemical biology. 9(4):904-12 [DOI] 10.1021/cb400875u. [PMID] 24506227.
2014
Two-dimensional combinatorial screening enables the bottom-up design of a microRNA-10b inhibitor.
Chemical communications (Cambridge, England). 50(23):3027-9 [DOI] 10.1039/c3cc00173c. [PMID] 24503738.
2013
A dynamic structural model of expanded RNA CAG repeats: a refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations.
Journal of the American Chemical Society. 135(9):3528-38 [DOI] 10.1021/ja3108627. [PMID] 23441937.
2013
A superfolding Spinach2 reveals the dynamic nature of trinucleotide repeat-containing RNA.
Nature methods. 10(12):1219-24 [DOI] 10.1038/nmeth.2701. [PMID] 24162923.
2013
Covalent small-molecule-RNA complex formation enables cellular profiling of small-molecule-RNA interactions.
Angewandte Chemie (International ed. in English). 52(38):10010-3 [DOI] 10.1002/anie.201301639. [PMID] 23913698.
2013
Defining RNA motif-aminoglycoside interactions via two-dimensional combinatorial screening and structure-activity relationships through sequencing.
Bioorganic & medicinal chemistry. 21(20):6132-8 [DOI] 10.1016/j.bmc.2013.04.072. [PMID] 23719281.
2013
Features of modularly assembled compounds that impart bioactivity against an RNA target.
ACS chemical biology. 8(10):2312-21 [DOI] 10.1021/cb400265y. [PMID] 24032410.
2013
Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules.
Nature communications. 4 [DOI] 10.1038/ncomms3044. [PMID] 23806903.
2013
Rational design of chemical genetic probes of RNA function and lead therapeutics targeting repeating transcripts.
Drug discovery today. 18(23-24):1228-36 [DOI] 10.1016/j.drudis.2013.07.024. [PMID] 23939337.
2013
Sequestration of DROSHA and DGCR8 by expanded CGG RNA repeats alters microRNA processing in fragile X-associated tremor/ataxia syndrome.
Cell reports. 3(3):869-80 [DOI] 10.1016/j.celrep.2013.02.004. [PMID] 23478018.
2013
Small-molecule-mediated cleavage of RNA in living cells.
Angewandte Chemie (International ed. in English). 52(5):1462-5 [DOI] 10.1002/anie.201206888. [PMID] 23280953.
2012
A small molecule that targets r(CGG)(exp) and improves defects in fragile X-associated tremor ataxia syndrome.
ACS chemical biology. 7(10):1711-8 [DOI] 10.1021/cb300135h. [PMID] 22948243.
2012
Chemical correction of pre-mRNA splicing defects associated with sequestration of muscleblind-like 1 protein by expanded r(CAG)-containing transcripts.
ACS chemical biology. 7(3):496-505 [DOI] 10.1021/cb200413a. [PMID] 22252896.
2012
Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching.
Journal of the American Chemical Society. 134(10):4731-42 [DOI] 10.1021/ja210088v. [PMID] 22300544.
2012
Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations.
Nature communications. 3 [DOI] 10.1038/ncomms2119. [PMID] 23047683.
2012
Probing a 2-aminobenzimidazole library for binding to RNA internal loops via two-dimensional combinatorial screening.
ACS chemical biology. 7(11):1902-9 [DOI] 10.1021/cb300213g. [PMID] 22958065.
2012
Rational design of bioactive, modularly assembled aminoglycosides targeting the RNA that causes myotonic dystrophy type 1.
ACS chemical biology. 7(12):1984-93 [DOI] 10.1021/cb3001606. [PMID] 23130637.
2012
Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive.
ACS chemical biology. 7(5):856-62 [DOI] 10.1021/cb200408a. [PMID] 22332923.
2012
Recent advances in developing small molecules targeting RNA.
ACS chemical biology. 7(1):73-86 [DOI] 10.1021/cb200447r. [PMID] 22185671.
2012
Studying modification of aminoglycoside antibiotics by resistance-causing enzymes via microarray.
Methods in molecular biology (Clifton, N.J.). 808:303-20 [DOI] 10.1007/978-1-61779-373-8_21. [PMID] 22057534.
2011
A crystal structure of a model of the repeating r(CGG) transcript found in fragile X syndrome.
Chembiochem : a European journal of chemical biology. 12(14):2140-2 [DOI] 10.1002/cbic.201100337. [PMID] 21766409.
2011
Defining the RNA internal loops preferred by benzimidazole derivatives via 2D combinatorial screening and computational analysis.
Journal of the American Chemical Society. 133(26):10111-8 [DOI] 10.1021/ja200212b. [PMID] 21604752.
2011
Influencing uptake and localization of aminoglycoside-functionalized peptoids.
Molecular bioSystems. 7(8):2441-51 [DOI] 10.1039/c1mb05074e. [PMID] 21611644.
2011
Molecular recognition of 6′-N-5-hexynoate kanamycin A and RNA 1×1 internal loops containing CA mismatches.
Biochemistry. 50(6):962-9 [DOI] 10.1021/bi101724h. [PMID] 21207945.
2011
Myotonic dystrophy type 1 RNA crystal structures reveal heterogeneous 1 × 1 nucleotide UU internal loop conformations.
Biochemistry. 50(45):9928-35 [DOI] 10.1021/bi2013068. [PMID] 21988728.
2011
NMR spectroscopy and molecular dynamics simulation of r(CCGCUGCGG)₂ reveal a dynamic UU internal loop found in myotonic dystrophy type 1.
Biochemistry. 50(5):599-601 [DOI] 10.1021/bi101896j. [PMID] 21204525.
2011
Using modularly assembled ligands to bind RNA internal loops separated by different distances.
Chembiochem : a European journal of chemical biology. 12(14):2143-6 [DOI] 10.1002/cbic.201100298. [PMID] 21830289.
2010
A chemoenzymatic route to diversify aminoglycosides enables a microarray-based method to probe acetyltransferase activity.
Chembiochem : a European journal of chemical biology. 11(12):1656-60 [DOI] 10.1002/cbic.201000300. [PMID] 20629012.
2010
A microarray-based method to perform nucleic acid selections.
Methods in molecular biology (Clifton, N.J.). 669:209-24 [DOI] 10.1007/978-1-60761-845-4_17. [PMID] 20857369.
2010
Structure-activity relationships through sequencing (StARTS) defines optimal and suboptimal RNA motif targets for small molecules.
Angewandte Chemie (International ed. in English). 49(22):3816-8 [DOI] 10.1002/anie.200907257. [PMID] 20397174.
2010
The Privileged Chemical Space Predictor (PCSP): a computer program that identifies privileged chemical space from screens of modularly assembled chemical libraries.
Bioorganic & medicinal chemistry letters. 20(4):1338-43 [DOI] 10.1016/j.bmcl.2010.01.017. [PMID] 20097562.
2010
The role of flexibility in the rational design of modularly assembled ligands targeting the RNAs that cause the myotonic dystrophies.
Chembiochem : a European journal of chemical biology. 11(3):375-82 [DOI] 10.1002/cbic.200900716. [PMID] 20058255.
2010
Two-dimensional combinatorial screening of a bacterial rRNA A-site-like motif library: defining privileged asymmetric internal loops that bind aminoglycosides.
Biochemistry. 49(9):1833-42 [DOI] 10.1021/bi901998m. [PMID] 20108982.
2009
Controlling the specificity of modularly assembled small molecules for RNA via ligand module spacing: targeting the RNAs that cause myotonic muscular dystrophy.
Journal of the American Chemical Society. 131(47):17464-72 [DOI] 10.1021/ja906877y. [PMID] 19904940.
2009
Rational and modular design of potent ligands targeting the RNA that causes myotonic dystrophy 2.
ACS chemical biology. 4(5):345-55 [DOI] 10.1021/cb900025w. [PMID] 19348464.
2009
Rational design of ligands targeting triplet repeating transcripts that cause RNA dominant disease: application to myotonic muscular dystrophy type 1 and spinocerebellar ataxia type 3.
Journal of the American Chemical Society. 131(28):9767-79 [DOI] 10.1021/ja9020149. [PMID] 19552411.
2009
Small molecule microarrays of RNA-focused peptoids help identify inhibitors of a pathogenic group I intron.
ACS chemical biology. 4(4):299-307 [DOI] 10.1021/cb800313m. [PMID] 19278238.
2009
Two-dimensional combinatorial screening and the RNA Privileged Space Predictor program efficiently identify aminoglycoside-RNA hairpin loop interactions.
Nucleic acids research. 37(17):5894-907 [DOI] 10.1093/nar/gkp594. [PMID] 19726586.
2008
A simple ligation-based method to increase the information density in sequencing reactions used to deconvolute nucleic acid selections.
RNA (New York, N.Y.). 14(2):390-4 [PMID] 18065718.
2008
Short-circuiting RNA splicing.
Nature chemical biology. 4(12):723-4 [DOI] 10.1038/nchembio1208-723. [PMID] 19008883.
2008
Studying aminoglycoside modification by the acetyltransferase class of resistance-causing enzymes via microarray.
Carbohydrate research. 343(17):2924-31 [DOI] 10.1016/j.carres.2008.08.018. [PMID] 18774127.
2008
Two-dimensional combinatorial screening identifies specific 6′-acylated kanamycin A- and 6′-acylated neamine-RNA hairpin interactions.
Biochemistry. 47(48):12670-9 [DOI] 10.1021/bi8012615. [PMID] 18991404.
2008
Two-dimensional combinatorial screening identifies specific aminoglycoside-RNA internal loop partners.
Journal of the American Chemical Society. 130(33):11185-94 [DOI] 10.1021/ja803234t. [PMID] 18652457.
2007
“Supra”molecular recognition of Galectin 1.
Chemistry & biology. 14(10):1095-7 [PMID] 17961821.
2007
A small molecule microarray platform to select RNA internal loop-ligand interactions.
ACS chemical biology. 2(11):745-54 [PMID] 17975888.
2007
An aminoglycoside microarray platform for directly monitoring and studying antibiotic resistance.
Biochemistry. 46(40):11223-30 [PMID] 17867707.
2007
Using selection to identify and chemical microarray to study the RNA internal loops recognized by 6′-N-acylated kanamycin A.
Chembiochem : a European journal of chemical biology. 8(6):649-56 [PMID] 17394189.
2006
A mannan binding lectin is involved in cell-cell attachment in a toxic strain of Microcystis aeruginosa.
Molecular microbiology. 59(3):893-906 [PMID] 16420359.
2006
Chemical microarrays to identify ligands that bind pathogenic cells.
Chembiochem : a European journal of chemical biology. 7(12):1882-5 [PMID] 17009274.
2006
Miniaturization of microwave-assisted carbohydrate functionalization to create oligosaccharide microarrays.
Chembiochem : a European journal of chemical biology. 7(3):421-4 [PMID] 16444768.
2005
Activity of Hoechst 33258 against Pneumocystis carinii f. sp. muris, Candida albicans, and Candida dubliniensis.
Antimicrobial agents and chemotherapy. 49(4):1326-30 [PMID] 15793106.
2005
N-linked glycosylated beta-peptides are resistant to degradation by glycoamidase A.
Chemistry & biodiversity. 2(12):1624-34 [PMID] 17191959.
2004
Aminoglycoside microarrays to explore interactions of antibiotics with RNAs and proteins.
Chemistry (Weinheim an der Bergstrasse, Germany). 10(13):3308-14 [PMID] 15224340.
2004
Aminoglycoside microarrays to study antibiotic resistance.
Angewandte Chemie (International ed. in English). 43(12):1591-4 [PMID] 15022242.
2004
Detection of bacteria with carbohydrate-functionalized fluorescent polymers.
Journal of the American Chemical Society. 126(41):13343-6 [PMID] 15479090.
2004
Hoechst 33258 selectively inhibits group I intron self-splicing by affecting RNA folding.
Chembiochem : a European journal of chemical biology. 5(12):1647-52 [PMID] 15532034.
2004
Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure.
Proceedings of the National Academy of Sciences of the United States of America. 101(19):7287-92 [PMID] 15123812.
2004
New approaches to targeting RNA with oligonucleotides: inhibition of group I intron self-splicing.
Biopolymers. 73(1):151-61 [PMID] 14691946.
2004
The use of carbohydrate microarrays to study carbohydrate-cell interactions and to detect pathogens.
Chemistry & biology. 11(12):1701-7 [PMID] 15610854.
2004
Tools for glycomics: mapping interactions of carbohydrates in biological systems.
Chembiochem : a European journal of chemical biology. 5(10):1375-83 [PMID] 15457538.
2003
Hybridization-based unquenching of DNA hairpins on au surfaces: prototypical “molecular beacon” biosensors.
Journal of the American Chemical Society. 125(14):4012-3 [PMID] 12670198.
2003
Uptake and antifungal activity of oligonucleotides in Candida albicans.
Proceedings of the National Academy of Sciences of the United States of America. 100(4):1530-4 [PMID] 12552085.
2002
Molecular recognition by the Candida albicans group I intron: tertiary interactions with an imino G.A pair facilitate binding of the 5′ exon and lower the KM for guanosine.
Biochemistry. 41(25):8113-9 [PMID] 12069604.
2002
Oligonucleotide directed misfolding of RNA inhibits Candida albicans group I intron splicing.
Proceedings of the National Academy of Sciences of the United States of America. 99(17):11091-6 [PMID] 12169671.
2001
Binding enhancement by tertiary interactions and suicide inhibition of a Candida albicans group I intron by phosphoramidate and 2′-O-methyl hexanucleotides.
Biochemistry. 40(21):6520-6 [PMID] 11371215.
2001
Recognition elements for 5′ exon substrate binding to the Candida albicans group I intron.
Biochemistry. 40(21):6507-19 [PMID] 11371214.
2000
Contributions of individual nucleotides to tertiary binding of substrate by a Pneumocystis carinii group I intron.
Biochemistry. 39(46):14269-78 [PMID] 11087376.
2000
Targeting a Pneumocystis carinii group I intron with methylphosphonate oligonucleotides: backbone charge is not required for binding or reactivity.
Biochemistry. 39(23):6991-7000 [PMID] 10841781.
1999
Thermodynamics of RNA-RNA duplexes with 2- or 4-thiouridines: implications for antisense design and targeting a group I intron.
Biochemistry. 38(50):16655-62 [PMID] 10600128.

Grants

Apr 2022 ACTIVE
Design of precision small molecules targeting RNA repeating transcripts to manipulate and study disease biology
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Apr 2022 ACTIVE
RNA-Targeted Drug Discovery and Development for Parkinson's Disease
Role: Principal Investigator
Funding: RUTGERS STATE UNIV via NATL INST OF HLTH NINDS
Apr 2022 ACTIVE
Targeted degradation of RNAs by using small molecules
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Apr 2022 ACTIVE
Design and Study of Small Molecules That Cleave the RNA That Causes Myotonic Dystrophy Type 1 (DM1)
Role: Principal Investigator
Funding: US ARMY MED RES ACQUISITION
Apr 2022 ACTIVE
Small Molecules That Target the RNAs That Cause Pulmonary Fibrosis and Polycystic Kidney Disease
Role: Principal Investigator
Funding: US ARMY MED RES ACQUISITION
Apr 2022 ACTIVE
Small Molecule Targeting of mRNAs Encoding Proteins relevant for Cardiovascular, Renal and Metabolic Diseases
Role: Principal Investigator
Funding: ASTRAZENECA
Apr 2022 ACTIVE
Pathophysiology of genetically defined dementia and neurodegeneration: Defining therapeutic targets and pathways
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Apr 2022 ACTIVE
Developing Pre-Clinical Candidates Against miRNAs Implicated in Autoimmune Diseases
Role: Principal Investigator
Funding: EMD SERONO RESEARCH & DEVELOPMENT INST
Apr 2022 ACTIVE
Small Molecule Targeting of DUX4 mRNA for treatment of Fascioscapulohumeral Dystrophy (FSHD)
Role: Principal Investigator
Funding: PFIZER INC

Education

Ph.D. in Biophysical Chemistry
2003 · University of Rochester
Master's of Science in Chemistry
1999 · University of Rochester
Bachelor's of Science in Chemistry
1997 · University of Maryland, College Park

Contact Details

Phones:
Business:
(561) 228-2000
Emails:
Business:
mdisney@ufl.edu
Addresses:
Business Mailing:
120 SCRIPPS WAY
JUPITER FL 33458