Matthew D. Disney, PhD

Department of Chemistry
Florida Campus

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

The Disney group is focused on developing rational and predictable approaches to design highly selective therapeutics from only genome sequence. One of the major articulations of the utility of genome sequencing efforts has been in advancing patient-specific therapies, yet such developments have been only sparsely reported.

We accomplish this lofty goal by using advancements in annotating RNA structure from sequence and several novel technologies that we have recently developed in our laboratory. Our current focus is on leveraging these technological advances to identify patient-specific therapies targeting orphan diseases that have no known cure or more common disorders to which there is a poor prognosis, such as drug resistant cancers.

Key advances that we have recently reported include:

(i) Developing lead therapeutics that improve defects associated with the most common adult-onset forms of muscular dystrophy (Myotonic Dystrophy Types 1 and 2) in both animal and cellular models of disease.

(ii) Designing compounds that target the most common single gene cause of Autism (Fragile X Syndrome) and an adult-onset disease called Fragile X-Associated Tremor Ataxia Syndrome that occurs in older individuals that carry a shortened version of the Fragile X Syndrome genetic defect.  These studies have advanced our understanding of novel roles of RNA-mediated gene silencing and in identifying and exploiting novel drug targets.

(iii) Targeting the genetic defect that causes Huntington’s disease, which is an incurable disorder that causes muscle decline and cognitive issues.

(iv) Correcting RNA processing defects that are caused by RNA mutations in Parkinsonism and Frontotemporal Dementia (FTDP-17).

(v) Developing specific lead therapeutics that reduce the production of toxic proteins that are known to cause the majority of cases of Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig’s disease) and Frontotemporal Dementia

(vi) Designing precise therapeutics that specifically kill a variety of Cancers that have a poor prognosis with current chemotherapeutics

(vii) Exploiting important classes of drug targets in multiple disorders that are viewed as being impossible to “drug”

(viii) Developing and implementing novel technologies that allow for the precise reaction and cleavage of RNA targets by using small molecules to both identify and further manipulate therapeutically relevant RNAs by small molecules. 


Ph.D. (Biophysical Chemistry), University of Rochester, 2003
M.S. (Chemistry), University of Rochester, 1999
B.S. (Chemistry), University of Maryland, College Park, 1997

Professional Experience

2005-2010 Assistant Professor, University at Buffalo, The State University of New York
2002-2005 Postdoctoral Fellow, Swiss Federal Institute of Technology Zurich (ETH)

Awards & Professional Activities

2018 - Barry Cohen Prize. Awarded by the Medicinal Chemistry Section of the Israel Chemical Society and Teva Pharmaceutical Industries. 

2017 - Scripps Florida Outstanding Mentor Award. 

2016 - Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry.

2015 - NIH Director’s Pioneer Award.

2015, 2016, 2017 - Blavatnik Young Scientists Award Finalist.

2014 - David W. Robertson Award in Medicinal Chemistry. Awarded by the American  Chemical Society’s Division of Medicinal Chemistry for having a primary role in the discovery of a novel therapeutic agents, targets, theoretical concepts in medicinal chemistry or drug discovery, and making a significant scientific discovery that enhances the field of medicinal chemistry.

2013 - Excellence Award in the field of Research in Science and Technology. India-US Chamber of Commerce, Inc., South Florida.  

2013 - Eli Lilly Award in Biological Chemistry from American Chemical Society in recognition of outstanding research in biological chemistry of unusual merit and independence of thought and originality.

2012 - David Gin Award in Carbohydrate Chemistry from the American Chemical Society in recognition of excellence in carbohydrate chemistry from a new investigator.

May 2010 - University at Buffalo, Excellent Scholar, Young Investigator Award.

May 2010 – April 2015 - Dreyfus Teacher-Scholar Award.

July 2008 – June 2010 - Research Corporation Cottrell Scholar Award.

July 2007 – June 2009 - NYSTAR JD Watson Young Investigator Award.

September 2005 – August 2010 - Camille and Henry Dreyfus New Faculty Award.

June 2004 – January 2005 - Second Year Roche Foundation Post doctoral Fellowship; Swiss Federal Institute of Technology (ETH, Zürich).

June 2003 – May 2004 - Roche Foundation Post doctoral Fellowship; Swiss Federal Institute of Technology (ETH, Zürich).

2001 – 2002 - Arnold Weissberger Memorial Fellow; University of Rochester.

2000 – 2001 - Elon Huntington Hooker Memorial Fellow; University of Rochester.

1997 – 1999 - Sherman-Clark Memorial Fellow; University of Rochester.

1997- Eric A. Batista Award; University of Maryland, College Park. Award for most outstanding undergraduate research.

1995 – 1997- Howard Hughes Medical Institute Undergraduate Research Fellow; University of Maryland, College Park.

Selected References

All Publications

Small Molecule Targeted Recruitment of a Nuclease to RNA. Costales MG, Matsumoto Y, Velagapudi SP, Disney MDJ Am Chem Soc. 2018 May 24. doi: 10.1021/jacs.8b01233. [Epub ahead of print]. PMID: 29792692.

Using Genome Sequence to Enable the Design of Medicines and Chemical Probes. Angelbello AJ, Chen JL, Childs-Disney JL, Zhang P, Wang ZF, Disney MDChem Rev. 2018 Feb 28;118(4):1599-1663. doi: 10.1021/acs.chemrev.7b00504. Epub 2018 Jan 11. PMID: 29322778.

Bleomycin Can Cleave an Oncogenic Noncoding RNA. Angelbello AJ, Disney MD. Chembiochem. 2017 Oct 30. doi: 10.1002/cbic.201700581. [Epub ahead of print] PubMed PMID: 29084369.

Small molecule alteration of RNA sequence in cells and animals. Guan L, Luo Y, Ja WW, Disney MD. Bioorg Med Chem Lett. 2017 Oct 18. pii: S0960-894X(17)31018-1. doi: 10.1016/j.bmcl.2017.10.034. [Epub ahead of print] PubMed PMID: 29079470.

Structure and Dynamics of RNA Repeat Expansions That Cause Huntington's Disease and Myotonic Dystrophy Type 1. Chen JL, VanEtten DM, Fountain MA, Yildirim I, Disney MDBiochemistry. 2017 Jul 11;56(27):3463-3474.

Inhibiting Translation One Protein at a Time. Disney MDTrends Biochem Sci. 2017 Jun;42(6):412-413.

Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA. Velagapudi SP, Luo Y, Tran T, Haniff HS, Nakai Y, Fallahi M, Martinez GJ, Childs-Disney JL, Disney MDACS Cent Sci. 2017 Mar 22;3(3):205-216.

Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis. Gendron TF, Chew J, Stankowski JN, Hayes LR, Zhang YJ, Prudencio M, Carlomagno Y, Daughrity LM, Jansen-West K, Perkerson EA, O'Raw A, Cook C, Pregent L, Belzil V, van Blitterswijk M, Tabassian LJ, Lee CW, Yue M, Tong J, Song Y, Castanedes-Casey M, Rousseau L, Phillips V, Dickson DW, Rademakers R, Fryer JD, Rush BK, Pedraza O, Caputo AM, Desaro P, Palmucci C, Robertson A, Heckman MG, Diehl NN, Wiggs E, Tierney M, Braun L, Farren J, Lacomis D, Ladha S, Fournier CN, McCluskey LF, Elman LB, Toledo JB, McBride JD, Tiloca C, Morelli C, Poletti B, Solca F, Prelle A, Wuu J, Jockel-Balsarotti J, Rigo F, Ambrose C, Datta A, Yang W, Raitcheva D, Antognetti G, McCampbell A, Van Swieten JC, Miller BL, Boxer AL, Brown RH, Bowser R, Miller TM, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Traynor BJ, Disney MD, Benatar M, Silani V, Glass JD, Floeter MK, Rothstein JD, Boylan KB, Petrucelli L. Sci Transl Med. 2017 Mar 29;9(383). pii: eaai7866.

Small Molecule Inhibition of microRNA-210 Reprograms an Oncogenic Hypoxic Circuit. Costales MG, Haga CL, Velagapudi SP, Childs-Disney JL, Phinney DG, Disney MDJ Am Chem Soc. 2017 Mar 8;139(9):3446-3455.

Rational Design of Small Molecules Targeting Oncogenic Noncoding RNAs from Sequence. Disney MD, Angelbello AJ. Acc Chem Res. 2016 Dec 20;49(12):2698-2704.

Precise small-molecule recognition of a toxic CUG RNA repeat expansion. Rzuczek SG, Colgan LA, Nakai Y, Cameron MD, Furling D, Yasuda R, Disney MDNat Chem Biol. 2017 Feb;13(2):188-193.

Rapid Generation of miRNA Inhibitor Leads by Bioinformatics and Efficient High-Throughput Screening Methods. Haga CL, Velagapudi SP, Childs-Disney JL, Strivelli J, Disney MD, Phinney DG. Methods Mol Biol. 2017;1517:179-198.

Development of pharmacophore models for small molecules targeting RNA: Application to the RNA repeat expansion in myotonic dystrophy type 1. Angelbello AJ, González ÀL, Rzuczek SG, Disney MDBioorg Med Chem Lett. 2016 Dec 1;26(23):5792-5796.

Controlled dehydration improves the diffraction quality of two RNA crystals. Park H, Tran T, Lee JH, Park H, Disney MDBMC Struct Biol. 2016 Nov 3;16(1):19.

Corrigendum: A Toxic RNA Catalyzes the In Cellulo Synthesis of Its Own Inhibitor. Rzuczek SG, Park H, Disney MDAngew Chem Int Ed Engl. 2016 Aug 16;55(34):9817. 

Chemistry and Chemical Biology of Therapeutically Important Compounds. Disney MDBioorg Med Chem. 2016 Sep 1;24(17):3875. 

Small Molecule Recognition and Tools to Study Modulation of r(CGG)(exp) in Fragile X-Associated Tremor Ataxia Syndrome. Yang WY, He F, Strack RL, Oh SY, Frazer M, Jaffrey SR, Todd PK, Disney MDACS Chem Biol. 2016 Sep 16;11(9):2456-65. 

Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10. Yang WY, Gao R, Southern M, Sarkar PS, Disney MDNat Commun. 2016 Jun 1;7:11647.

Design of a small molecule against an oncogenic noncoding RNA. Velagapudi SP, Cameron MD, Haga CL, Rosenberg LH, Lafitte M, Duckett DR, Phinney DG, Disney MDProc Natl Acad Sci U S A. 2016 May 24;113(21):5898-903. 

Comparison of small molecules and oligonucleotides that target a toxic, non-coding RNA. Costales MG, Rzuczek SG, Disney MDBioorg Med Chem Lett. 2016 Jun 1;26(11):2605-9. 

Inforna 2.0: A Platform for the Sequence-Based Design of Small Molecules Targeting Structured RNAs. Disney MD, Winkelsas AM, Velagapudi SP, Southern M, Fallahi M, Childs-Disney JL. ACS Chem Biol. 2016 Jun 17;11(6):1720-8. 

Analysis of secondary structural elements in human microRNA hairpin precursors. Liu B, Childs-Disney JL, Znosko BM, Wang D, Fallahi M, Gallo SM, Disney MDBMC Bioinformatics. 2016 Mar 1;17:112.

Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma. Childs-Disney JL, Disney MDACS Chem Biol. 2016 Feb 19;11(2):375-80.

Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells. Childs-Disney JL, Disney MDAnnu Rev Pharmacol Toxicol. 2016;56:123-40. 


The RNA Drug Hunters

Creative Minds: Can Diseased Cells Help to Make Their Own Drugs?

Targeting RNA

Podcast on rational design of small molecules targeting RNAs that cause incurable disease

Rational design of small molecules targeting incurable disease II

Rational design of small molecules targeting incurable disease

Highlight of our work on targeting toxic RNAs III

Highlight of our work on targeting toxic RNAs II

Highlight of our work on targeting toxic RNAs

Highlight on our work to target RNA Defects in Huntington's and other diseases

Podcast on our work on developing drugs for Myotonic Muscular Dystrophy

MMD Research: Blocking Harmful Interactions